By Drew Halley
A revolutionary new procedure for stem cell transplant is reversing the effects of severe adult sickle cell disease. For years, adults suffering from sickle cell anemia have relied on consistent blood transfusions and drug treatments to combat the disorder. Bone marrow transplants can reverse sickle cell, but have so far been restricted to children in the early stages of the disease. That is, until now.
Sickle cell anemia is a congenital blood disorder that affects all races, but is most common to persons with African ancestry, affecting about 72,000 in the US and millions worldwide. Red blood cells normally take the shape of a doughnut without its hole; in the blood of sickle cell patients, the cells assume an abnormal sickle shape. Sickle cells block small blood vessels and inhibit blood flow, which causes debilitating pain, damages organs and increases the risk of stroke. Many of the risks of sickle cell can be mediated through early diagnosis, dietary supplements, and drug treatment. But even with modern treatment, life expectancy for sickle cell patients is 42 in males, 48 in females. Some severe cases are resistant to existent therapies and can cut life even shorter.
Because red blood cells are produced in bone marrow, some high-risk children qualify for marrow transplants from a suitable sibling donor. Like all organ transplants, the procedure carries the danger of immune rejection, and so requires immunosuppressant drugs in addition to radiation therapy to kill diseased marrow. Transplants have been traditionally restricted to children, whose organs are comparably stronger than adults who suffer from the disease. Transplants are rare – there have been about 200 in the past few decades – and are attempted only in children whose disorders are life-threatening.
But a new procedure developed by the National Institute of Health (NIH) and Johns Hopkins University has successfully transplanted marrow to adults, reversing the disorder in 9 out of 10 patients. The new treatment uses significantly less radiation (about one fourth) to kill the patient’s existent marrow, combined with the immunosuppressant drug Sirolimus to reduce the likelihood of transplant rejection. By allowing more of the patient’s own marrow to remain, recovery from the transplant is faster and healthier (patients could previously spend months in germ-free isolation while their immune systems recovered). Thirty months after the transplant, the nine patients with successful transplants are healthy and show no side effects.
Many adults with sickle cell anemia take the drug hydroxyurea to treat the disorder. Hydroxyurea works by stimulating the body to produce a form of hemoglobin normally only found during development in the womb. The production of this hemoglobin type helps to balance the proportion of healthy vs. sickle cells in the blood, and reduces the damage done to lungs, kidneys, and liver (not to mention the risk of stroke). But hydroxyurea doesn’t work for all adult patients, making the prospect of adult marrow transplant a much-needed form of alternative therapy.
Kelly Halloway, the first half-match donation recipient at the National Institute of Health
So far, most adult patients who have received marrow transplants have had “full match” donors – siblings with a fully compatible genetic makeup. The chances of a sibling being fully matched are only 25%. But new procedures are expanding the pool of potential donors to “half match” donors, which includes parents and improves the likelihood of a compatible sibling to 75%. That means more sources of transplant marrow, and a better shot at a successful reversal of the disease.
Future research will aim to expand marrow transplants beyond sickle cell patients. Several other congenital blood diseases could conceivably be treated with marrow transplants, including such debilitating disorders as beta-thalassemia.Researchers are currently exploring the emerging possibilities of adult marrow transplants, and will doubtless yield more amazing treatments in coming years
Clear, honest information for people living with thalassemia — and the people who love them
Jun 14, 2010
Jun 11, 2010
Indians at Risk for Rare Blood Disorder Thalassemia
By LISA TSERING
indiawest.com
Indian Americans are at greater risk of contracting thalassemia than many other ethnic groups, according to a study by the Children’s Hospital and Research Center Oakland in Oakland, Calif. To coincide with International Thalassemia Day May 8, the hospital is urging the community to get tested — and to seriously consider banking their infants’ cord blood.
The rare and hereditary blood disorder can result in severe anemia. Children with thalassemia often require frequent blood transfusions and lifelong medical treatment.
Gargi Pahuja, a health care law attorney in New York, was diagnosed with thalassemia when she was 12 months old. “My parents were from India and they hadn’t heard of it,” Pahuja told India-West in a phone interview. “They were shocked to find that they carried the trait.”
Since thalassemia is so rare, some doctors are likely to confuse its symptoms, which include yellow skin, with jaundice. But thalassemia is a much more serious disease.
Thalassemia (also known as Mediterranean anemia) is an inherited blood disorder characterized by less hemoglobin and fewer red blood cells in the body than normal. Since hemoglobin allows red blood cells to carry oxygen, a deficiency leads to anemia, marked by fatigue, pale appearance, shortness of breath and weakness.
Pahuja is 35 years old, and continues to get blood transfusions every two weeks.
“The fact that I’m 35 is an important milestone,” she told India-West. “My parents were told that I would die by the age of 15 … my generation is the first to live into their 30s, 40s and 50s.”
The cause of thalassemia is defects in the genes that make hemoglobin. The only way to contract thalassemia is to inherit one or more defective hemoglobin genes from your parents.
Infants in California are required to receive a test for thalassemia, but California is the only state to require the test, said Pahuja.
Bone marrow transplant is the established treatment to cure thalassemia. Umbilical cord blood stem cells donated by a sibling have been proven to cure 91 percent of cases, according to a 2007 Children’s Hospital study of 40 children.
A Mayo Clinic statement said that most children with moderate to severe thalassemia show signs within the first two years of life. Prenatal testing is also available, at 11 weeks (chorionic villus sampling), 16 weeks (amniocentesis), and 18 weeks (fetal blood sampling).
“People need to be tested so that they can make informed decisions regarding family planning,” said Pahuja.
The Children’s Hospital study showed that in the United States, around two million people are carriers and that around 1,000 people have the full-blown disease. The hospital has one of the largest thalassemia centers on the West Coast, and currently treats around 300 patients.
In the U.S., there are more than 5,000 thalassemia cases, and those numbers are expected
to rise as the trait carrier population increases, said the study; in Alameda County alone, the Asian Indian population is more than 47,000 and has increased by 209 percent in the last decade, according to statistics provided by the Asian American Pacific Islander Health Forum.
According to Pahuja — who says she has devoted her professional and personal life to increasing awareness of thalassemia — people from North India are especially at risk. “If you are Punjabi, or Gujarati, or Sindhi, you need to get tested,” she told India-West. Individuals who are past child-bearing age need not get tested, she added.
In India, as many as one in eight people are believed to be carriers of the thalassemia gene, and in India, it is expected that 1 million people will have the disease in the next 40 years. Babies born there are 80-90 percent likely to die of the disease, said the Children’s Hospital spokesperson. But increasing awareness of the disease there has opened up a market for blood cord banking; a recent Mumbai Mirror article states that there are now three private stem cell banks — one run by Reliance in Mumbai; the CryoCell stem bank in New Delhi; and Life Cell, run in collaboration with Cryo-Cell International, U.S.A., in Chennai.
In India, it costs around Rs. 70,000 ($1,575) to preserve a newborn’s cord blood for 20 years. Here in the United States, the average cost is around $2,000.
indiawest.com
Indian Americans are at greater risk of contracting thalassemia than many other ethnic groups, according to a study by the Children’s Hospital and Research Center Oakland in Oakland, Calif. To coincide with International Thalassemia Day May 8, the hospital is urging the community to get tested — and to seriously consider banking their infants’ cord blood.
The rare and hereditary blood disorder can result in severe anemia. Children with thalassemia often require frequent blood transfusions and lifelong medical treatment.
Gargi Pahuja, a health care law attorney in New York, was diagnosed with thalassemia when she was 12 months old. “My parents were from India and they hadn’t heard of it,” Pahuja told India-West in a phone interview. “They were shocked to find that they carried the trait.”
Since thalassemia is so rare, some doctors are likely to confuse its symptoms, which include yellow skin, with jaundice. But thalassemia is a much more serious disease.
Thalassemia (also known as Mediterranean anemia) is an inherited blood disorder characterized by less hemoglobin and fewer red blood cells in the body than normal. Since hemoglobin allows red blood cells to carry oxygen, a deficiency leads to anemia, marked by fatigue, pale appearance, shortness of breath and weakness.
Pahuja is 35 years old, and continues to get blood transfusions every two weeks.
“The fact that I’m 35 is an important milestone,” she told India-West. “My parents were told that I would die by the age of 15 … my generation is the first to live into their 30s, 40s and 50s.”
The cause of thalassemia is defects in the genes that make hemoglobin. The only way to contract thalassemia is to inherit one or more defective hemoglobin genes from your parents.
Infants in California are required to receive a test for thalassemia, but California is the only state to require the test, said Pahuja.
Bone marrow transplant is the established treatment to cure thalassemia. Umbilical cord blood stem cells donated by a sibling have been proven to cure 91 percent of cases, according to a 2007 Children’s Hospital study of 40 children.
A Mayo Clinic statement said that most children with moderate to severe thalassemia show signs within the first two years of life. Prenatal testing is also available, at 11 weeks (chorionic villus sampling), 16 weeks (amniocentesis), and 18 weeks (fetal blood sampling).
“People need to be tested so that they can make informed decisions regarding family planning,” said Pahuja.
The Children’s Hospital study showed that in the United States, around two million people are carriers and that around 1,000 people have the full-blown disease. The hospital has one of the largest thalassemia centers on the West Coast, and currently treats around 300 patients.
In the U.S., there are more than 5,000 thalassemia cases, and those numbers are expected
to rise as the trait carrier population increases, said the study; in Alameda County alone, the Asian Indian population is more than 47,000 and has increased by 209 percent in the last decade, according to statistics provided by the Asian American Pacific Islander Health Forum.
According to Pahuja — who says she has devoted her professional and personal life to increasing awareness of thalassemia — people from North India are especially at risk. “If you are Punjabi, or Gujarati, or Sindhi, you need to get tested,” she told India-West. Individuals who are past child-bearing age need not get tested, she added.
In India, as many as one in eight people are believed to be carriers of the thalassemia gene, and in India, it is expected that 1 million people will have the disease in the next 40 years. Babies born there are 80-90 percent likely to die of the disease, said the Children’s Hospital spokesperson. But increasing awareness of the disease there has opened up a market for blood cord banking; a recent Mumbai Mirror article states that there are now three private stem cell banks — one run by Reliance in Mumbai; the CryoCell stem bank in New Delhi; and Life Cell, run in collaboration with Cryo-Cell International, U.S.A., in Chennai.
In India, it costs around Rs. 70,000 ($1,575) to preserve a newborn’s cord blood for 20 years. Here in the United States, the average cost is around $2,000.
Signs of Anemia in an Infant
By:Ashley Waters Gordon
Overview
Anemia is a common blood disorder in infants, affecting normal growth and development. The most common type in babies under two years of age is iron-deficiency anemia. With iron-deficiency anemia, the infant either does not get enough iron or cannot absorb iron. Lack of iron lowers the number of healthy red blood cells. These contain hemoglobin, which carries oxygen to organs and tissues. A growing baby needs this oxygen for organs to develop properly. Signs of infant anemia can be hard to see until the case is more severe, so have your baby tested at routine doctor's appointments. Call your infant's pediatrician right away if you notice any of the below symptoms.
Paleness of Skin, Lips and Nail Beds
Look for paleness in your baby's skin, lips or nail beds. Paleness tells you that not enough red blood cells and oxygen are circulating in your baby's blood. Some babies can even take on a gray or blue tone in very serious cases. You may not be able to notice paleness in infants until they have significant anemia, typically hemoglobin levels greater than 7 grams per deciliter (g/dL). Schedule an appointment for your baby to see his pediatrician if you notice paleness.
Growth or Developmental Delays
Pay attention to any delays in your baby's growth and development. These delays may be signs of anemia. Delayed growth and development can happen when the baby's organs, like the heart or the brain, do not getting enough oxygen to grow properly. Talk with your baby's pediatrician at his next appointment if you feel that your baby is not growing at the same rate or is not reaching normal developmental milestones.
Jaundice
Anemic babies can develop a condition called jaundice. You will be able to see jaundice when the infant's skin or whites of the eyes turn a yellow color. The buildup of a substance called bilirubin causes this yellowing. This happens when the baby's body breaks down too many old red blood cells, making a large amount of bilirubin. The baby's liver can filter out a normal amount of bilirubin each day. When there is a high number of red blood cells broken down and more bilirubin than the liver can handle, your infant's skin begins to turn yellow. Call your baby's pediatrician immediately if you notice any yellowing of the skin so that she can begin treating your baby's jaundice and anemia.
Rapid Heartbeat or New Heart Murmur
Pay attention to heart changes. When not enough oxygen is getting to your baby's tissues and organs, her body may compensate by raising her heart rate. The heart tries to pump more blood and oxygen to tissues throughout her body. Stress on the heart can cause a murmur. Ask the pediatrician if anemia could be causing your baby's increased heart rate or new murmur. If anemia could be the cause, have your infant's blood tested for anemia.
Decreased Appetite
Babies with anemia become tired easily and may be too weak to properly suck. If you notice your baby has a decreased appetite, begin taking notes of how often and for how long your baby nurses. Or, if your baby drinks formula, make note of the volume of formula your baby drinks at each feeding. Share this information with your pediatrician.
Excessive Sleeping or Fatigue
If your baby sleeps an excessive amount, call your pediatrician. This can be a sign of anemia. Because he does not have enough oxygen in his blood, an anemic baby may be too weak to play or remain awake for normal periods of time. Keep a journal of how long your baby sleeps in a 24-hour period. When your baby is awake, make notes on how active he stays. Show the pediatrician your notes to help diagnose and treat any possible anemia.
Irritability
Does your baby seem unusually cranky when she is awake? If she has anemia, your infant may be over-tired, or hungry but too weak to eat. This can make a baby become more irritable than normal. Ask your doctor if your baby's irritability maybe a sign of underlying anemia.
Overview
Anemia is a common blood disorder in infants, affecting normal growth and development. The most common type in babies under two years of age is iron-deficiency anemia. With iron-deficiency anemia, the infant either does not get enough iron or cannot absorb iron. Lack of iron lowers the number of healthy red blood cells. These contain hemoglobin, which carries oxygen to organs and tissues. A growing baby needs this oxygen for organs to develop properly. Signs of infant anemia can be hard to see until the case is more severe, so have your baby tested at routine doctor's appointments. Call your infant's pediatrician right away if you notice any of the below symptoms.
Paleness of Skin, Lips and Nail Beds
Look for paleness in your baby's skin, lips or nail beds. Paleness tells you that not enough red blood cells and oxygen are circulating in your baby's blood. Some babies can even take on a gray or blue tone in very serious cases. You may not be able to notice paleness in infants until they have significant anemia, typically hemoglobin levels greater than 7 grams per deciliter (g/dL). Schedule an appointment for your baby to see his pediatrician if you notice paleness.
Growth or Developmental Delays
Pay attention to any delays in your baby's growth and development. These delays may be signs of anemia. Delayed growth and development can happen when the baby's organs, like the heart or the brain, do not getting enough oxygen to grow properly. Talk with your baby's pediatrician at his next appointment if you feel that your baby is not growing at the same rate or is not reaching normal developmental milestones.
Jaundice
Anemic babies can develop a condition called jaundice. You will be able to see jaundice when the infant's skin or whites of the eyes turn a yellow color. The buildup of a substance called bilirubin causes this yellowing. This happens when the baby's body breaks down too many old red blood cells, making a large amount of bilirubin. The baby's liver can filter out a normal amount of bilirubin each day. When there is a high number of red blood cells broken down and more bilirubin than the liver can handle, your infant's skin begins to turn yellow. Call your baby's pediatrician immediately if you notice any yellowing of the skin so that she can begin treating your baby's jaundice and anemia.
Rapid Heartbeat or New Heart Murmur
Pay attention to heart changes. When not enough oxygen is getting to your baby's tissues and organs, her body may compensate by raising her heart rate. The heart tries to pump more blood and oxygen to tissues throughout her body. Stress on the heart can cause a murmur. Ask the pediatrician if anemia could be causing your baby's increased heart rate or new murmur. If anemia could be the cause, have your infant's blood tested for anemia.
Decreased Appetite
Babies with anemia become tired easily and may be too weak to properly suck. If you notice your baby has a decreased appetite, begin taking notes of how often and for how long your baby nurses. Or, if your baby drinks formula, make note of the volume of formula your baby drinks at each feeding. Share this information with your pediatrician.
Excessive Sleeping or Fatigue
If your baby sleeps an excessive amount, call your pediatrician. This can be a sign of anemia. Because he does not have enough oxygen in his blood, an anemic baby may be too weak to play or remain awake for normal periods of time. Keep a journal of how long your baby sleeps in a 24-hour period. When your baby is awake, make notes on how active he stays. Show the pediatrician your notes to help diagnose and treat any possible anemia.
Irritability
Does your baby seem unusually cranky when she is awake? If she has anemia, your infant may be over-tired, or hungry but too weak to eat. This can make a baby become more irritable than normal. Ask your doctor if your baby's irritability maybe a sign of underlying anemia.
May 24, 2010
Study Looks at Pregnancy in Thalassemia
A recent study published in Haematologica (Vol. 95, Issue 3) examined pregnancy in women with thalassemia.
Entitled "Pregnancy and Beta-thalassemia: an Italian multicenter experience," the paper examined 58 pregnancies among 47 women with thalassemia major and 17 pregnancies in women with thalassemia intermedia at four centers in Italy. The study reports that conception was spontaneous in all of those with thalassemia intermedia; among those with thalassemia major, gonadotrophin-induced ovulation was required in 33 of the women.
According to the study, 91% of the pregnancies among alassemia major patients resulted in live births (45 single births, 5 sets of twins, one set of triplets). The authors also report that no secondary complications of iron overload developed or worsened during pregnancy. There was a higher prevalence of pre-term births (32.8%), but the authors state that this was primarily related to multiple pregnancies and precautionary measures. Women with thalassemia intermedia who had never been transfused or who had only minimal transfusion prior to pregnancy were found to be at risk of severe alloimmune anemia if transfusions were required during pregnancy. (Decreased hemoglobin levels necessitated transfusion in 11 of the 17 thalassemia intermedia pregnancies.) Of the 17 pregnancies in thalassemia intermedia known to the researchers, 15 resulted in live births.
The authors also state that "cardiac function was not impaired during pregnancy." One patient did experience worsening of T2* scores, but the authors suggest that this was due to the timing of the second MRI reading; as it was taken one month after delivery, the patient was still off chelation. The authors also stated that "it is strongly recommended that thalassemic women wishing to become pregnant undergo a complete evaluation of organ iron overload, including MRI T2* and SQUID, prior to pregnancy." (In the United States, Ferriscan/R2 readings are often used for liver iron rather than those provided by SQUID, together with T2* cardiac assessment.)
The study concludes that "provided a multidisciplinary team is available, pregnancy is possible, safe and usually has a favorable outcome in patients with thalassemia." The authors are state the need for larger and more detailed studies, especially in thalassemia intermedia.
Download CAF's "Fertility and Pregnancy in Thalassemia" pamphlet by clicking here
Entitled "Pregnancy and Beta-thalassemia: an Italian multicenter experience," the paper examined 58 pregnancies among 47 women with thalassemia major and 17 pregnancies in women with thalassemia intermedia at four centers in Italy. The study reports that conception was spontaneous in all of those with thalassemia intermedia; among those with thalassemia major, gonadotrophin-induced ovulation was required in 33 of the women.
According to the study, 91% of the pregnancies among alassemia major patients resulted in live births (45 single births, 5 sets of twins, one set of triplets). The authors also report that no secondary complications of iron overload developed or worsened during pregnancy. There was a higher prevalence of pre-term births (32.8%), but the authors state that this was primarily related to multiple pregnancies and precautionary measures. Women with thalassemia intermedia who had never been transfused or who had only minimal transfusion prior to pregnancy were found to be at risk of severe alloimmune anemia if transfusions were required during pregnancy. (Decreased hemoglobin levels necessitated transfusion in 11 of the 17 thalassemia intermedia pregnancies.) Of the 17 pregnancies in thalassemia intermedia known to the researchers, 15 resulted in live births.
The authors also state that "cardiac function was not impaired during pregnancy." One patient did experience worsening of T2* scores, but the authors suggest that this was due to the timing of the second MRI reading; as it was taken one month after delivery, the patient was still off chelation. The authors also stated that "it is strongly recommended that thalassemic women wishing to become pregnant undergo a complete evaluation of organ iron overload, including MRI T2* and SQUID, prior to pregnancy." (In the United States, Ferriscan/R2 readings are often used for liver iron rather than those provided by SQUID, together with T2* cardiac assessment.)
The study concludes that "provided a multidisciplinary team is available, pregnancy is possible, safe and usually has a favorable outcome in patients with thalassemia." The authors are state the need for larger and more detailed studies, especially in thalassemia intermedia.
Download CAF's "Fertility and Pregnancy in Thalassemia" pamphlet by clicking here
May 20, 2010
Pathway Genomics personal genetic testing kits to be sold at Walgreens
Pathway Genomics (www.PATHWAY.com), a U.S.-based genetic testing company, today announced that Pathway's personal genetic testing kits will be available at Walgreens. Starting in mid-May the Pathway Genomics Insight™ Saliva Collection Kit will be sold at many of Walgreens' nearly 7,500 stores nationwide (with the exception of New York, due to a New York state law). The Insight™ Saliva Collection Kit will retail in the $20 to $30 price range.
“We're revolutionizing the way people access information about their genetics, and through thousands of convenient Walgreens locations, we're making it easier and more affordable than ever before to order a personalized genetic report”
The Insight™ Saliva Collection Kit contains a small saliva collection kit, simple instructions, and a postage-paid envelope that customers can use to send their saliva sample back to the Pathway Genomics laboratory. From there, they simply visit Pathway's web site (www.PATHWAY.com) to create their own secure, password-protected account and order an individualized Genetic Insight™ Report for Drug Response ($79), Pre-Pregnancy Planning ($179), Health Conditions ($179) or a combination of all three ($249). Pathway's Genetics Insight™ Reports offer consumers a convenient and affordable way to learn about their personal genetics.
"We're revolutionizing the way people access information about their genetics, and through thousands of convenient Walgreens locations, we're making it easier and more affordable than ever before to order a personalized genetic report," said Jim Plante, CEO of Pathway Genomics. "The value of knowing how genes play a role in our personal lives, and potentially the lives of our children, is critical for making well-informed health and wellness decisions."
Pathway Genomics believes that personalized genetic reports are quickly becoming a critical component for providing useful insight into a person's DNA make up and genetic data. For instance, a Pathway Genomics Genetic Insight™ Report can provide a wide range of information to help an individual learn about their health and make healthier lifestyle choices.For example, with a Pathway Genomics Genetic Insight™ Report for prescription medications, people can discover if due to their genetic traits, they are more or less sensitive to a variety of treatment therapies.
Pathway Genomics Genetic Insight™ Reports are ordered separately from the Insight™ Saliva Collection Kit by logging on to www.PATHWAY.com. Reports available include a Drug Response Insight™ for just $79, a Pre-Pregnancy Planning Insight™ for $179, a Health Conditions Insight™ for $179, or a Total Health Insight™ combining three genetic reports for $249.
“We're revolutionizing the way people access information about their genetics, and through thousands of convenient Walgreens locations, we're making it easier and more affordable than ever before to order a personalized genetic report”
The Insight™ Saliva Collection Kit contains a small saliva collection kit, simple instructions, and a postage-paid envelope that customers can use to send their saliva sample back to the Pathway Genomics laboratory. From there, they simply visit Pathway's web site (www.PATHWAY.com) to create their own secure, password-protected account and order an individualized Genetic Insight™ Report for Drug Response ($79), Pre-Pregnancy Planning ($179), Health Conditions ($179) or a combination of all three ($249). Pathway's Genetics Insight™ Reports offer consumers a convenient and affordable way to learn about their personal genetics.
"We're revolutionizing the way people access information about their genetics, and through thousands of convenient Walgreens locations, we're making it easier and more affordable than ever before to order a personalized genetic report," said Jim Plante, CEO of Pathway Genomics. "The value of knowing how genes play a role in our personal lives, and potentially the lives of our children, is critical for making well-informed health and wellness decisions."
Pathway Genomics believes that personalized genetic reports are quickly becoming a critical component for providing useful insight into a person's DNA make up and genetic data. For instance, a Pathway Genomics Genetic Insight™ Report can provide a wide range of information to help an individual learn about their health and make healthier lifestyle choices.For example, with a Pathway Genomics Genetic Insight™ Report for prescription medications, people can discover if due to their genetic traits, they are more or less sensitive to a variety of treatment therapies.
Pathway Genomics Genetic Insight™ Reports are ordered separately from the Insight™ Saliva Collection Kit by logging on to www.PATHWAY.com. Reports available include a Drug Response Insight™ for just $79, a Pre-Pregnancy Planning Insight™ for $179, a Health Conditions Insight™ for $179, or a Total Health Insight™ combining three genetic reports for $249.
May 19, 2010
Dispelling the stigma attached to blood disorder
Prakash Jaga, 23, from Sherwood was diagnosed with thalassaemia when he was a baby.
Thalassaemia is a genetic disorder of the blood that causes a form of anaemia, decreasing the number of red blood cells. The condition is hereditary and mainly affects those of Mediterranean descent and is also common in the Arabian Peninsula, Iran, Pakistan and southern China.
In South Africa, it is found mainly in those of Indian descent as well as in the Greek, Italian and Portuguese communities.
There are approximately 250 to 300 Indians in the country who have the blood condition.
There are two types of thalassaemia - minor, a less severe form where patients present a mild form of anaemia and major, a chronic condition requiring lifelong medical intervention.
The disorder is inherited from both parents who are carriers of thalassaemia minor. Parents who are carriers have a one-in-four chance of passing on the condition to their children.
Treatment of the condition requires a lifelong cycle of blood transfusion every three to four weeks for the rest of the patient's life.
Dr Yasmin Goga, a paediatric haematology consultant, said the condition presented itself between the ages of six months to a year. She said without treatment it would eventually lead to car-diac failure and death within the first two years of an affected child's life.
Last week Saturday marked World Thalassaemia Day. As a result, Jaga and the South African Thalassaemia Association are aiming to raise more awareness about the condition.
Jaga said when he told people about it, they assumed that, because it was a blood disorder, it was related to Aids.
"A lot of people are ignorant. They hear about it and then take a step back from me because they think it's contagious. I have had women who have been out with me and when I tell them, they take a step back. They think it's something similar to Aids."
But Jaga said having the condition has not prevented him from living a normal, full life.
"You get used to living with it. Initially it is a shock for parents and it's hard for the child to get used to it because you are getting injected every three weeks with a drip.
"But you slowly adjust to it and you come to realise that, if you don't do it, you will die. Without the blood transfusion you become weak and oxygen stops running in your body and your organs will give up."
He said with the help of the association they were trying to educate people about the disorder.
Jaga, who works in administration for a travel company, said every three weeks he took a day off work to get his treatment done, saying some days were "good" while others were "tiring".
He said people needed to have a positive outlook on life. "There is a lot that you can do. If you are on the treatment, you can live a long and happy life. If people ask you about it, educate them."
With transfusions every week, thalassaemia patients suffer with iron overload which gets deposited in their liver and can eventually lead to cardiac failure. In an attempt to prevent this, the patient is injected five times a week.
However, because of the invasive manner of the injections a new drug was developed, which is taken orally. The South African Thalassaemia Association campaigned for the drug to be made available to South Africans in 2006.
Sunil Soni, chairperson of the association, said the core function of the group was to provide patients and extended families with support regarding the treatment of the disorder. He said the condition could cost approximately R300000 a year.
"The condition is very complicated, so we have the association to improve the quality of life for all living with it. There is not enough awareness about this condition."
Soni said the condition was sometimes misdiagnosed and presented as anaemia.
"There are many people who are carrying the gene but they don't know it. So our duty is to empower people so that they can make educated decisions about the future of their family."
Thalassaemia is a genetic disorder of the blood that causes a form of anaemia, decreasing the number of red blood cells. The condition is hereditary and mainly affects those of Mediterranean descent and is also common in the Arabian Peninsula, Iran, Pakistan and southern China.
In South Africa, it is found mainly in those of Indian descent as well as in the Greek, Italian and Portuguese communities.
There are approximately 250 to 300 Indians in the country who have the blood condition.
There are two types of thalassaemia - minor, a less severe form where patients present a mild form of anaemia and major, a chronic condition requiring lifelong medical intervention.
The disorder is inherited from both parents who are carriers of thalassaemia minor. Parents who are carriers have a one-in-four chance of passing on the condition to their children.
Treatment of the condition requires a lifelong cycle of blood transfusion every three to four weeks for the rest of the patient's life.
Dr Yasmin Goga, a paediatric haematology consultant, said the condition presented itself between the ages of six months to a year. She said without treatment it would eventually lead to car-diac failure and death within the first two years of an affected child's life.
Last week Saturday marked World Thalassaemia Day. As a result, Jaga and the South African Thalassaemia Association are aiming to raise more awareness about the condition.
Jaga said when he told people about it, they assumed that, because it was a blood disorder, it was related to Aids.
"A lot of people are ignorant. They hear about it and then take a step back from me because they think it's contagious. I have had women who have been out with me and when I tell them, they take a step back. They think it's something similar to Aids."
But Jaga said having the condition has not prevented him from living a normal, full life.
"You get used to living with it. Initially it is a shock for parents and it's hard for the child to get used to it because you are getting injected every three weeks with a drip.
"But you slowly adjust to it and you come to realise that, if you don't do it, you will die. Without the blood transfusion you become weak and oxygen stops running in your body and your organs will give up."
He said with the help of the association they were trying to educate people about the disorder.
Jaga, who works in administration for a travel company, said every three weeks he took a day off work to get his treatment done, saying some days were "good" while others were "tiring".
He said people needed to have a positive outlook on life. "There is a lot that you can do. If you are on the treatment, you can live a long and happy life. If people ask you about it, educate them."
With transfusions every week, thalassaemia patients suffer with iron overload which gets deposited in their liver and can eventually lead to cardiac failure. In an attempt to prevent this, the patient is injected five times a week.
However, because of the invasive manner of the injections a new drug was developed, which is taken orally. The South African Thalassaemia Association campaigned for the drug to be made available to South Africans in 2006.
Sunil Soni, chairperson of the association, said the core function of the group was to provide patients and extended families with support regarding the treatment of the disorder. He said the condition could cost approximately R300000 a year.
"The condition is very complicated, so we have the association to improve the quality of life for all living with it. There is not enough awareness about this condition."
Soni said the condition was sometimes misdiagnosed and presented as anaemia.
"There are many people who are carrying the gene but they don't know it. So our duty is to empower people so that they can make educated decisions about the future of their family."
May 10, 2010
An easy way to prevent Thalassemia
Dr. Shantha Hettiarachchi
The marriage is expressed by the most of Sri Lankans as Bamba ketoo hati in their words. It means that the marriage is decided through unseen powers such as Brahma.
Prior to the marriage, matching of the partners will take place according to their ethnic and religious concepts too. Nevertheless, it may get revealed that this type of matching, is incomplete when the couple get a new born baby with hereditary disorders. Hence, a few more matching of marital partners should be completed to avoid these easily preventable problems.
Thalassemia represent a higher position in the list of preventable hereditary disorder through screening, clinical matching and marriage counseling. It has a long history, over 50,000 years in the world. Thalassemia is derived from a Greek word of Thalasa means ‘sea’ because it was found in a valley south of Italy and Greece covered by the Mediterranean sea.
The Thalassemias are the commonest inherited haematological disorders and also the commonest single gene disorders in the world population. It is also a major cause of mortality and morbidity in South East Asian region. It is a significant burden to the health services and economy of many countries.
A basic knowledge on blood and anaemia is necessary to understand about thalassemia. The blood consists of cells and the liquid part of plasma. The white blood cells, red blood cells and platelets represent the cellular elements of the blood. A red coloured, oxygen carrying pigment, called hemoglobin is found in the red blood cells. Hemoglobin is essential for body metabolism as it carries oxygen to the cells of every tissues and organs. A person will develop anaemia, when there is a decrease in the level of hemoglobin in the blood below the reference level for the age and sex.
This genetic hemotological disorder of thalassemia is characterized by absent or decreased production of normal hemoglobin, resulting an anaemia. The hemoglobin molecule consists of a hem and globin. The protein moiety of globin synthesis is impaired, as there is a mutation of the genes in thalassemia. According to these mutations, synthesis of the main globin chains, namely alpha and beta is markedly reduced. Eventually, it leads to a decreased production of haemoglobin with anaemia. Then the disease state is named as beta thalassemia or alpha thalassemia, depending on the relevant type of globin chain, production of which is impaired due to this disorder.
There are two forms of thalassemia, called as thalassemia major with clinical manifestations and thalassemia minor without clinical manifestations. Thalassemia major is a severe inherited childhood anemia in which hemoglobin synthesis is highly inadequate. These children are normal at birth but become grossly anaemic within the first year of life with failure to grow, poor feeding, intermittent fever and delay in improving from recurrent infective illnesses.
They need regular blood transfusions in life to avoid fatal complications and to secure optimum growth and development. As the red blood cells in the transfused blood are broken down, the iron released from these cells are accumulated in their body. The overload of iron can damage the vital organs, such as heart, liver and pancreas to cause heart failure, liver disease and diabetes. Therefore iron chelation therapy with the drugs such as Desferrioxamine has to be continued concurrently with blood transfusion to avoid these complications by removing extra iron from the body.
The persons with thalassaemia minor, known as carriers of thalassemia are healthy and normal but some of them can manifest milder degree of anemia. This carrier stage is commonly discovered while they are undergoing a test of blood picture for some other circumstances.
The beta thalassemia is the most important form of thalassemia, causing a major public health problem in many countries. It was estimated that 1.5 percent of world population are carriers of beta thalassemia and around 70,000 beta thalassemic babies are born annually.
The alpha thalassemias are commoner than the beta thalassemias but the consequent public health problems are less as the mild form of the disease do not produce major disabilities.
Currently, more than 2500 children are living with thalassaemia major in Sri Lanka. The highest number of patients are reporting in Kurunagala, Kandy, Anuradhapura and Badulla districts. About one hundred new patients are accumulating to the total number annually.
The country has to allocate 7 percent to 10 percent from total health expenditure for the clinical management, necessary for these patients. It was stated that the expenditure is around ten million rupees in managing one thalassaemic patient in a lifetime.
If both partners are thalassemic carriers there will be a 25 percent chance of giving birth to baby with thalassemia. If the thalassemic carrier marries a normal partner there will be no risk of getting a thalassemic baby.
There is no possibility in having a thalassemic baby, when there is a marriage between a thalassemic patient and a normal partner too. Therefore, prevention from thalassemia is not a difficult task if the people have a basic knowledge on these simple scientific facts.
The thalassemia carrier state could be identified by simple blood tests. It is very important to know whether they are carriers of the disease prior to marriage, especially when they are living in areas with high prevalence of thalassemia, such as North central, North Western, Uva, Central and Western provinces of Sri Lanka.
The one essential act to avoid is the marriage between two thalassaemic carriers. As the facilities in screening for thalassemia and counseling are currently available provincially, the public will have the responsibility to use these services wisely.
May 8 marks the World Thalassemia Day. It should be noted that the quality of life of the thalassemic patients, is improving from day to day with the advances in treatment. While giving proper care to the people who has developed the disease, every body should try their level best to prevent the disease.
The marriage is expressed by the most of Sri Lankans as Bamba ketoo hati in their words. It means that the marriage is decided through unseen powers such as Brahma.
Prior to the marriage, matching of the partners will take place according to their ethnic and religious concepts too. Nevertheless, it may get revealed that this type of matching, is incomplete when the couple get a new born baby with hereditary disorders. Hence, a few more matching of marital partners should be completed to avoid these easily preventable problems.
Thalassemia represent a higher position in the list of preventable hereditary disorder through screening, clinical matching and marriage counseling. It has a long history, over 50,000 years in the world. Thalassemia is derived from a Greek word of Thalasa means ‘sea’ because it was found in a valley south of Italy and Greece covered by the Mediterranean sea.
The Thalassemias are the commonest inherited haematological disorders and also the commonest single gene disorders in the world population. It is also a major cause of mortality and morbidity in South East Asian region. It is a significant burden to the health services and economy of many countries.
A basic knowledge on blood and anaemia is necessary to understand about thalassemia. The blood consists of cells and the liquid part of plasma. The white blood cells, red blood cells and platelets represent the cellular elements of the blood. A red coloured, oxygen carrying pigment, called hemoglobin is found in the red blood cells. Hemoglobin is essential for body metabolism as it carries oxygen to the cells of every tissues and organs. A person will develop anaemia, when there is a decrease in the level of hemoglobin in the blood below the reference level for the age and sex.
This genetic hemotological disorder of thalassemia is characterized by absent or decreased production of normal hemoglobin, resulting an anaemia. The hemoglobin molecule consists of a hem and globin. The protein moiety of globin synthesis is impaired, as there is a mutation of the genes in thalassemia. According to these mutations, synthesis of the main globin chains, namely alpha and beta is markedly reduced. Eventually, it leads to a decreased production of haemoglobin with anaemia. Then the disease state is named as beta thalassemia or alpha thalassemia, depending on the relevant type of globin chain, production of which is impaired due to this disorder.
There are two forms of thalassemia, called as thalassemia major with clinical manifestations and thalassemia minor without clinical manifestations. Thalassemia major is a severe inherited childhood anemia in which hemoglobin synthesis is highly inadequate. These children are normal at birth but become grossly anaemic within the first year of life with failure to grow, poor feeding, intermittent fever and delay in improving from recurrent infective illnesses.
They need regular blood transfusions in life to avoid fatal complications and to secure optimum growth and development. As the red blood cells in the transfused blood are broken down, the iron released from these cells are accumulated in their body. The overload of iron can damage the vital organs, such as heart, liver and pancreas to cause heart failure, liver disease and diabetes. Therefore iron chelation therapy with the drugs such as Desferrioxamine has to be continued concurrently with blood transfusion to avoid these complications by removing extra iron from the body.
The persons with thalassaemia minor, known as carriers of thalassemia are healthy and normal but some of them can manifest milder degree of anemia. This carrier stage is commonly discovered while they are undergoing a test of blood picture for some other circumstances.
The beta thalassemia is the most important form of thalassemia, causing a major public health problem in many countries. It was estimated that 1.5 percent of world population are carriers of beta thalassemia and around 70,000 beta thalassemic babies are born annually.
The alpha thalassemias are commoner than the beta thalassemias but the consequent public health problems are less as the mild form of the disease do not produce major disabilities.
Currently, more than 2500 children are living with thalassaemia major in Sri Lanka. The highest number of patients are reporting in Kurunagala, Kandy, Anuradhapura and Badulla districts. About one hundred new patients are accumulating to the total number annually.
The country has to allocate 7 percent to 10 percent from total health expenditure for the clinical management, necessary for these patients. It was stated that the expenditure is around ten million rupees in managing one thalassaemic patient in a lifetime.
If both partners are thalassemic carriers there will be a 25 percent chance of giving birth to baby with thalassemia. If the thalassemic carrier marries a normal partner there will be no risk of getting a thalassemic baby.
There is no possibility in having a thalassemic baby, when there is a marriage between a thalassemic patient and a normal partner too. Therefore, prevention from thalassemia is not a difficult task if the people have a basic knowledge on these simple scientific facts.
The thalassemia carrier state could be identified by simple blood tests. It is very important to know whether they are carriers of the disease prior to marriage, especially when they are living in areas with high prevalence of thalassemia, such as North central, North Western, Uva, Central and Western provinces of Sri Lanka.
The one essential act to avoid is the marriage between two thalassaemic carriers. As the facilities in screening for thalassemia and counseling are currently available provincially, the public will have the responsibility to use these services wisely.
May 8 marks the World Thalassemia Day. It should be noted that the quality of life of the thalassemic patients, is improving from day to day with the advances in treatment. While giving proper care to the people who has developed the disease, every body should try their level best to prevent the disease.
Apr 19, 2010
Pulmonary Hypertension in Thalassemia
Written by Craig Butler
Pulmonary Hypertension in Thalassemia
Pulmonary hypertension is a complication that occurs in some individuals with thalassemia. (Although it can occur in both thalassemia major and thalassemia intermedia, it is considered by CAF Medical Advisory Board Chair Ellis Neufeld to be a big problem in adults with intermedia and of possible rising significance in adults with major as they age.) Below, CAF speaks with Claudia R. Morris, MD, of Children’s Hospital and Research Center Oakland about pulmonary hypertension and thalassemia and about some current clinical trials in this area. These trials, which include a multi-center Thalassemia Clinical Research Network trial, are ongoing and are currently recruiting subjects.
CAF: Pulmonary hypertension is high blood pressure occurring in the arteries in the lungs. Why is this something which occurs in people with thalassemia, especially people with thalassemia intermedia? Is blood pressure in the lungs measured in a different method than “typical” blood pressure?
Dr. Morris: Pulmonary hypertension is a serious medical condition that can contribute to early death. There are many reasons why a patient with thalassemia may be at increased risk for developing pulmonary hypertension. Mechanisms that include:
• a history of splenectomy,
• the biological consequences of hemolysis (the breaking down of red blood cells),
• abnormal coagulation (the way that blood forms clots),
• iron overload from chronic blood transfusions with subsequent damage to the heart,
• inflammation and
• the effects of advancing age that deplete an individual’s ability to counterbalance oxidative stress
all contribute to this increased risk.
During hemolysis, molecules are released from the ruptured red blood cell that consume an important vasodilator called “nitric oxide.” (A vasodilator widens the blood vessels, allowing blood to travel more easily.) As nitric oxide levels decrease, vessels constrict, contributing to high blood pressures in the artery that connects the heart to the lungs. Sticky platelets and other clumping cells can lead to blood clots in these vessels called “pulmonary emboli,” which also cause increased blood pressure in the pulmonary arteries. It turns out that most medical conditions associated with hemolysis also have a high frequency of pulmonary hypertension. (Hemolysis is more of an issue in thalassemia intermedia, which is one reason why pulmonary hypertension tends to be more often associated with intermedia than major. -Ed.)
Blood pressure in the lungs is measured differently than a typical “blood pressure” performed on your arm. The gold standard test for pulmonary hypertension is a procedure called a right-side cardiac catheterization. This involves passing a thin flexible tube (catheter) into the right side of the heart, usually passing through vessels in the groin or arm. This study is done by a trained cardiologist. A Doppler echocardiogram (a non-invasive test to estimate pulmonary artery pressures that is functionally an ultrasound of your heart and lung vessels) is then conducted and used to identify patients who are at risk for having pulmonary hypertension.
Sildenafil is used to treat pulmonary hypertension in the non-thalassemic population. Is it used to treat other conditions as well? Are there any typical side effects that are currently thought to be associated with its use (in the non-thalassemic population)? Why can’t we just assume that sildenafil will be as safe for people with thalassemia as it is for other patients?
Sildenafil is one of over 10 medications that is FDA-approved to treat pulmonary hypertension. Although sildenafil is effective in treating pulmonary hypertension, it has not specifically been studied in patients with thalassemia. Thalassemia patients are different from patients with other forms of pulmonary hypertension (and thalassemia major is different from thalassemia intermedia), and these differences may affect the way they respond to certain medications. This is why studies determining the best way to treat pulmonary hypertension in patients with thalassemia are needed. (Since sildenafil does not at this point have a label indication for use in thalassemia, an organized clinical trial can provide a good, safe setting for a thalassemia patient to try sildenafil as a possible treatment option for pulmonary hypertension. - Ed.)
Also known as Viagra, sildenafil has gotten its reputation as a successful treatment for erectile dysfunction in addition to its role as a therapy for pulmonary hypertension. It is also used to treat high altitude sickness.
As with any medication, there are several side-effects that can occur with sildenafil use, although it is generally considered safe and well-tolerated. In clinical trials (which were not focused on the thalassemia population), the most common side effects included headache, flushing, dyspepsia (indigestion), nasal congestion and impaired vision, including photophobia (light sensitivity) and blurred vision. Rare cases of vision loss have been reported. Other rare but serious side effects include severe hypotension (abnormally low blood pressure), heart attack, stroke, heart arrhythmia and sudden hearing loss. It should not be taken with other nitric oxide donating medications (organic nitrites and nitrates, such as nitroglycerine, sodium nitroprusside, amyl nitrite).
Sildenafil is an oral medication. How is it ingested - as a pill or as a solution?
Sildenafil comes in both a pill and liquid form.
What are the reasons that a person with thalassemia might want to enroll a study for pulmonary hypertension?
There are several reasons why a patient might be interested in participating in clinical trials. Research is very important in order to advance science, contribute to the greater good, and improve medical insight into diseases like thalassemia in order to improve therapies in the future. In particular, if a patient has pulmonary hypertension, it would be of benefit to the patient to have the condition studied further.
Ongoing studies utilize several procedures as part of the study to help determine the most significant contributing factors causing pulmonary hypertension. Pulmonary hypertension is associated with a number of risk factors. It is likely the result of a combination of factors, including coagulation issues, iron overload and the long-term consequences of hemolysis.
Clinical trials help guide future therapy for patients with thalassemia dealing with pulmonary hypertension. It is possible that sildenafil or other FDA approved studies may help improve pulmonary hypertension, although we do not yet know if this therapy will work in patients with thalassemia. Control arms are often included in studies in order to determine the differences between patients who develop a complication like pulmonary hypertension from those who do not.
Researchers hope that this information gained from clinical trials will lead to improved therapies for patients with thalassemia in the future. Participation in clinical trials will insure that progress is made in both our understanding of this complication, and the best alternatives for treatment.
If you or someone you know has thalassemia and pulmonary hypertension, even if they are not interested in participation in a clinical trial, it is important that they see a cardiopulmonary specialist for further evaluation. Although guidelines for the treatment of pulmonary hypertension in thalassemia do not yet exist, specialists in pulmonary hypertension can help provide you with the best options to address this condition.
One pulmonary hypertension study currently under way is a multi-center trial run through the Thalassemia Clinical Research Network (TCRN) evaluating the safety and efficacy of sildenafil for pulmonary hypertension in Thalassemia. In addition to taking sildenafil 3 times a day, patients with pulmonary hypertension will undergo a series of tests during weeks 1, 2, 4, 8 and 12. Can you explain what is involved in these tests? Can all be completed on one day of each visit? Can you estimate the amount of time involved for the tests? And are there any special requirements (e.g., fasting, etc.) required by the tests?
The TCRN sildenafil study, is currently enrolling patients. The main goal of the sildenafil trial is to determine whether sildenafil improves exercise tolerance and walking distance in patients with an abnormal Doppler echo suggesting pulmonary hypertension.
Since you asked about the sildenafil trial, a summary of the procedures follows:
There are many procedures and blood tests that will be done as part of the sildenafil study. It can take 1-2 days to complete all the tests for baseline and final evaluations, while the 2 week evaluation will take several hours. No fasting is required for these tests. The tests and procedures are commonly performed as part of the clinical work-up for pulmonary hypertension.
Tests and Procedures:
• Medical history, review of symptoms and physical exam (performed at every visit)
• 6 minute walk test (performed at every visit): Involves walking around a predetermined path at a comfortable pace for 6 minutes to the distance walked in 6 minutes, which reflects exercise capacity.
• Doppler echocardiograph (week 0 and 12): Noninvasive ultrasound of heart and lung vessels
• Pulmonary Function Tests (week 0 and 12)
• Cardiac MRI (week 0 and 12)
• Chest CT (week 0)
• Blood tests (performed at every visit): Up to 2 tablespoons of blood will be drawn for multiple analyses
• Pregnancy test (in females, performed at every visit)
Another study focusing on pulmonary hypertension and thalassemia evaluates the safety and efficacy of a nutritional supplement called glutamine. It is an 8 week open-label study in patients with thalassemia and echocardiogram evidence of pulmonary hypertension, and involves study visits every 2 weeks, a blood draw and exercise tolerance test (6 minute walk test) at each visit, pulmonary function tests and a Doppler echo pre and post therapy.
The goal of this study is to determine if glutamine therapy replenishes the glutamine deficiency that occurs in the red blood cells of patients with pulmonary hypertension. This is a single center trial enrolling patients at Children’s Hospital & Research Center Oakland. More information on both studies and others targeting thalassemia can be found on
http://clinicaltrials.gov;
or specifically forthe sildenafil trial:
http://clinicaltrials.gov/ct2/show/NCT00872170?term=sildenafil+for+thalassemia&rank=1
and for the glutamine trial:
http://clinicaltrials.gov/ct2/results?term=glutamine+for+pulmonary+hypertension
I’m a little confused concerning what patients without pulmonary hypertension will be required to do in the TCRN sildenafil trial.
The listing states that the control group will attend one to three study visits at baseline; does that mean they will have all the same tests as the pulmonary hypertension group (plus lung function test, chest MRI, CAT, exhaled NO test), but that they might be spread out over two or three visits, rather than all performed at the same visit? And that they will not need to repeat the tests?
The baseline tests performed in patients with pulmonary hypertension will also be performed on control patients without pulmonary hypertension. If planned carefully these tests can all be done in one very busy day. Often it is spread over 2 days given scheduling challenges and the time it takes to have a Chest CT, heart MRI, Doppler echocardiogram, blood draw and 6 minute walk test preformed.
If a person wishes to participate, at what centers is the study being conducted? Who should s/he contact to learn more? Is there any funding available for people who might have transportation/location obstacles?
This is an NIH, NHLBI sponsored study run through the Thalassemia Clinical Research Network. Participating sites are in Boston, MA, New York City, NY, Philadelphia, PA Dallas, TX, Oakland, CA, and Toronto, Canada. Our London, UK and Beirut, Lebanon sites will hopefully be enrolling soon. Please contact Lisa Virzi, the Project Director, for information on the site nearest you, and possible availability of funding for travel if interested in participation.
Lisa Virzi
Project Director/TCRN Network Manager
New England Research Institutes
9 Galen Street
Watertown, MA 02472
Tel: 617- 923-7747 x258
email: lvirzi@neriscience.comThis e-mail address is being protected from spambots. You need JavaScript enabled to view it
Again, more information on these and other studies relevant to thalassemia can be found on clinicaltrials.gov.
I know this is hard to predict, but can you give a general idea of what would happen AFTER the TCRN study is completed, in a best case scenario?
This is a small pilot study. We are hoping to generate data that will lead to larger trials and guide future therapy for pulmonary hypertension in thalassemia. The results of this study will also provide new insight into the causes of pulmonary hypertension in patients with thalassemia. This information is vital in order to design specific therapies that target these specific mechanisms of disease. Best case scenario, this is the first step to better treatment options for patients with pulmonary hypertension and thalassemia.
Pulmonary Hypertension in Thalassemia
Pulmonary hypertension is a complication that occurs in some individuals with thalassemia. (Although it can occur in both thalassemia major and thalassemia intermedia, it is considered by CAF Medical Advisory Board Chair Ellis Neufeld to be a big problem in adults with intermedia and of possible rising significance in adults with major as they age.) Below, CAF speaks with Claudia R. Morris, MD, of Children’s Hospital and Research Center Oakland about pulmonary hypertension and thalassemia and about some current clinical trials in this area. These trials, which include a multi-center Thalassemia Clinical Research Network trial, are ongoing and are currently recruiting subjects.
CAF: Pulmonary hypertension is high blood pressure occurring in the arteries in the lungs. Why is this something which occurs in people with thalassemia, especially people with thalassemia intermedia? Is blood pressure in the lungs measured in a different method than “typical” blood pressure?
Dr. Morris: Pulmonary hypertension is a serious medical condition that can contribute to early death. There are many reasons why a patient with thalassemia may be at increased risk for developing pulmonary hypertension. Mechanisms that include:
• a history of splenectomy,
• the biological consequences of hemolysis (the breaking down of red blood cells),
• abnormal coagulation (the way that blood forms clots),
• iron overload from chronic blood transfusions with subsequent damage to the heart,
• inflammation and
• the effects of advancing age that deplete an individual’s ability to counterbalance oxidative stress
all contribute to this increased risk.
During hemolysis, molecules are released from the ruptured red blood cell that consume an important vasodilator called “nitric oxide.” (A vasodilator widens the blood vessels, allowing blood to travel more easily.) As nitric oxide levels decrease, vessels constrict, contributing to high blood pressures in the artery that connects the heart to the lungs. Sticky platelets and other clumping cells can lead to blood clots in these vessels called “pulmonary emboli,” which also cause increased blood pressure in the pulmonary arteries. It turns out that most medical conditions associated with hemolysis also have a high frequency of pulmonary hypertension. (Hemolysis is more of an issue in thalassemia intermedia, which is one reason why pulmonary hypertension tends to be more often associated with intermedia than major. -Ed.)
Blood pressure in the lungs is measured differently than a typical “blood pressure” performed on your arm. The gold standard test for pulmonary hypertension is a procedure called a right-side cardiac catheterization. This involves passing a thin flexible tube (catheter) into the right side of the heart, usually passing through vessels in the groin or arm. This study is done by a trained cardiologist. A Doppler echocardiogram (a non-invasive test to estimate pulmonary artery pressures that is functionally an ultrasound of your heart and lung vessels) is then conducted and used to identify patients who are at risk for having pulmonary hypertension.
Sildenafil is used to treat pulmonary hypertension in the non-thalassemic population. Is it used to treat other conditions as well? Are there any typical side effects that are currently thought to be associated with its use (in the non-thalassemic population)? Why can’t we just assume that sildenafil will be as safe for people with thalassemia as it is for other patients?
Sildenafil is one of over 10 medications that is FDA-approved to treat pulmonary hypertension. Although sildenafil is effective in treating pulmonary hypertension, it has not specifically been studied in patients with thalassemia. Thalassemia patients are different from patients with other forms of pulmonary hypertension (and thalassemia major is different from thalassemia intermedia), and these differences may affect the way they respond to certain medications. This is why studies determining the best way to treat pulmonary hypertension in patients with thalassemia are needed. (Since sildenafil does not at this point have a label indication for use in thalassemia, an organized clinical trial can provide a good, safe setting for a thalassemia patient to try sildenafil as a possible treatment option for pulmonary hypertension. - Ed.)
Also known as Viagra, sildenafil has gotten its reputation as a successful treatment for erectile dysfunction in addition to its role as a therapy for pulmonary hypertension. It is also used to treat high altitude sickness.
As with any medication, there are several side-effects that can occur with sildenafil use, although it is generally considered safe and well-tolerated. In clinical trials (which were not focused on the thalassemia population), the most common side effects included headache, flushing, dyspepsia (indigestion), nasal congestion and impaired vision, including photophobia (light sensitivity) and blurred vision. Rare cases of vision loss have been reported. Other rare but serious side effects include severe hypotension (abnormally low blood pressure), heart attack, stroke, heart arrhythmia and sudden hearing loss. It should not be taken with other nitric oxide donating medications (organic nitrites and nitrates, such as nitroglycerine, sodium nitroprusside, amyl nitrite).
Sildenafil is an oral medication. How is it ingested - as a pill or as a solution?
Sildenafil comes in both a pill and liquid form.
What are the reasons that a person with thalassemia might want to enroll a study for pulmonary hypertension?
There are several reasons why a patient might be interested in participating in clinical trials. Research is very important in order to advance science, contribute to the greater good, and improve medical insight into diseases like thalassemia in order to improve therapies in the future. In particular, if a patient has pulmonary hypertension, it would be of benefit to the patient to have the condition studied further.
Ongoing studies utilize several procedures as part of the study to help determine the most significant contributing factors causing pulmonary hypertension. Pulmonary hypertension is associated with a number of risk factors. It is likely the result of a combination of factors, including coagulation issues, iron overload and the long-term consequences of hemolysis.
Clinical trials help guide future therapy for patients with thalassemia dealing with pulmonary hypertension. It is possible that sildenafil or other FDA approved studies may help improve pulmonary hypertension, although we do not yet know if this therapy will work in patients with thalassemia. Control arms are often included in studies in order to determine the differences between patients who develop a complication like pulmonary hypertension from those who do not.
Researchers hope that this information gained from clinical trials will lead to improved therapies for patients with thalassemia in the future. Participation in clinical trials will insure that progress is made in both our understanding of this complication, and the best alternatives for treatment.
If you or someone you know has thalassemia and pulmonary hypertension, even if they are not interested in participation in a clinical trial, it is important that they see a cardiopulmonary specialist for further evaluation. Although guidelines for the treatment of pulmonary hypertension in thalassemia do not yet exist, specialists in pulmonary hypertension can help provide you with the best options to address this condition.
One pulmonary hypertension study currently under way is a multi-center trial run through the Thalassemia Clinical Research Network (TCRN) evaluating the safety and efficacy of sildenafil for pulmonary hypertension in Thalassemia. In addition to taking sildenafil 3 times a day, patients with pulmonary hypertension will undergo a series of tests during weeks 1, 2, 4, 8 and 12. Can you explain what is involved in these tests? Can all be completed on one day of each visit? Can you estimate the amount of time involved for the tests? And are there any special requirements (e.g., fasting, etc.) required by the tests?
The TCRN sildenafil study, is currently enrolling patients. The main goal of the sildenafil trial is to determine whether sildenafil improves exercise tolerance and walking distance in patients with an abnormal Doppler echo suggesting pulmonary hypertension.
Since you asked about the sildenafil trial, a summary of the procedures follows:
There are many procedures and blood tests that will be done as part of the sildenafil study. It can take 1-2 days to complete all the tests for baseline and final evaluations, while the 2 week evaluation will take several hours. No fasting is required for these tests. The tests and procedures are commonly performed as part of the clinical work-up for pulmonary hypertension.
Tests and Procedures:
• Medical history, review of symptoms and physical exam (performed at every visit)
• 6 minute walk test (performed at every visit): Involves walking around a predetermined path at a comfortable pace for 6 minutes to the distance walked in 6 minutes, which reflects exercise capacity.
• Doppler echocardiograph (week 0 and 12): Noninvasive ultrasound of heart and lung vessels
• Pulmonary Function Tests (week 0 and 12)
• Cardiac MRI (week 0 and 12)
• Chest CT (week 0)
• Blood tests (performed at every visit): Up to 2 tablespoons of blood will be drawn for multiple analyses
• Pregnancy test (in females, performed at every visit)
Another study focusing on pulmonary hypertension and thalassemia evaluates the safety and efficacy of a nutritional supplement called glutamine. It is an 8 week open-label study in patients with thalassemia and echocardiogram evidence of pulmonary hypertension, and involves study visits every 2 weeks, a blood draw and exercise tolerance test (6 minute walk test) at each visit, pulmonary function tests and a Doppler echo pre and post therapy.
The goal of this study is to determine if glutamine therapy replenishes the glutamine deficiency that occurs in the red blood cells of patients with pulmonary hypertension. This is a single center trial enrolling patients at Children’s Hospital & Research Center Oakland. More information on both studies and others targeting thalassemia can be found on
http://clinicaltrials.gov;
or specifically forthe sildenafil trial:
http://clinicaltrials.gov/ct2/show/NCT00872170?term=sildenafil+for+thalassemia&rank=1
and for the glutamine trial:
http://clinicaltrials.gov/ct2/results?term=glutamine+for+pulmonary+hypertension
I’m a little confused concerning what patients without pulmonary hypertension will be required to do in the TCRN sildenafil trial.
The listing states that the control group will attend one to three study visits at baseline; does that mean they will have all the same tests as the pulmonary hypertension group (plus lung function test, chest MRI, CAT, exhaled NO test), but that they might be spread out over two or three visits, rather than all performed at the same visit? And that they will not need to repeat the tests?
The baseline tests performed in patients with pulmonary hypertension will also be performed on control patients without pulmonary hypertension. If planned carefully these tests can all be done in one very busy day. Often it is spread over 2 days given scheduling challenges and the time it takes to have a Chest CT, heart MRI, Doppler echocardiogram, blood draw and 6 minute walk test preformed.
If a person wishes to participate, at what centers is the study being conducted? Who should s/he contact to learn more? Is there any funding available for people who might have transportation/location obstacles?
This is an NIH, NHLBI sponsored study run through the Thalassemia Clinical Research Network. Participating sites are in Boston, MA, New York City, NY, Philadelphia, PA Dallas, TX, Oakland, CA, and Toronto, Canada. Our London, UK and Beirut, Lebanon sites will hopefully be enrolling soon. Please contact Lisa Virzi, the Project Director, for information on the site nearest you, and possible availability of funding for travel if interested in participation.
Lisa Virzi
Project Director/TCRN Network Manager
New England Research Institutes
9 Galen Street
Watertown, MA 02472
Tel: 617- 923-7747 x258
email: lvirzi@neriscience.comThis e-mail address is being protected from spambots. You need JavaScript enabled to view it
Again, more information on these and other studies relevant to thalassemia can be found on clinicaltrials.gov.
I know this is hard to predict, but can you give a general idea of what would happen AFTER the TCRN study is completed, in a best case scenario?
This is a small pilot study. We are hoping to generate data that will lead to larger trials and guide future therapy for pulmonary hypertension in thalassemia. The results of this study will also provide new insight into the causes of pulmonary hypertension in patients with thalassemia. This information is vital in order to design specific therapies that target these specific mechanisms of disease. Best case scenario, this is the first step to better treatment options for patients with pulmonary hypertension and thalassemia.
Jun 15, 2009
"Thalassemia, Love and Needles"
A Day in the Life of Thalassemia Patient
Cooley's Anemia, also known as Thalassemia, is a fatal genetic blood disorder which affects people of Mediterranean descent. Today, in order to survive, children must receive blood transfusions every two weeks and receive painful drug injections via an infusion pump every night of their lives.
In its major form Cooley's Anemia is fatal. Over two million people in the United States are carriers of the minor form and do not even know it. The bad news is that these people are at risk in passing along the major form if they have children. The good news is that finally a cure is in sight.
WASHINGTON, D.C. - The AHEPA Cooley's Anemia Foundation released a documentary short that captures a young boy's daily battle against Thalassemia, a rare blood disorder that primarily affects, but is not limited to, individuals of Mediterranean descent, announced AHEPA Cooley's Anemia Foundation Chair Fanoula Gulas.
"Thalassemia, Love and Needles" is a five-minute video that profiles the life of Alex Gulas, who suffers from Thalassemia, also known as Cooley's Anemia. The viewer walks in the shoes of Alex as he undergoes medical treatment and blood transfusions all of which are essential to his survival.
"The documentary's purpose is to raise the level of awareness about this potentially fatal blood disorder by chronicling what a person must endure on a daily basis to survive," said Gulas, who is Alex's mother. "Obviously, our goal is to find a cure by supporting the scientific work of medical researchers working diligently to find one. We can only accomplish our goal with the community's assistance and support of medical research."
"Thalassemia, Love and Needles" is directed by George Carlos of Birmingham, Ala.
"We encourage you to share the documentary with family, friends, and colleagues to help us meet our mission," said Gulas. "We ask you keep the AHEPA Cooley's Anemia Foundation in your mind in the course of your charitable giving
AHEPA headquarters encourages all AHEPA Family chapters to reaffirm their commitment to finding a cure for Cooley's Anemia. Donations to help find a cure for Cooley's Anemia can be made online by visiting www.ahepaonline.com/contribute.aspx.
Cooley's Anemia, also known as Thalassemia, is a fatal genetic blood disorder which affects people of Mediterranean descent. Today, in order to survive, children must receive blood transfusions every two weeks and receive painful drug injections via an infusion pump every night of their lives.
In its major form Cooley's Anemia is fatal. Over two million people in the United States are carriers of the minor form and do not even know it. The bad news is that these people are at risk in passing along the major form if they have children. The good news is that finally a cure is in sight.
WASHINGTON, D.C. - The AHEPA Cooley's Anemia Foundation released a documentary short that captures a young boy's daily battle against Thalassemia, a rare blood disorder that primarily affects, but is not limited to, individuals of Mediterranean descent, announced AHEPA Cooley's Anemia Foundation Chair Fanoula Gulas.
"Thalassemia, Love and Needles" is a five-minute video that profiles the life of Alex Gulas, who suffers from Thalassemia, also known as Cooley's Anemia. The viewer walks in the shoes of Alex as he undergoes medical treatment and blood transfusions all of which are essential to his survival.
"The documentary's purpose is to raise the level of awareness about this potentially fatal blood disorder by chronicling what a person must endure on a daily basis to survive," said Gulas, who is Alex's mother. "Obviously, our goal is to find a cure by supporting the scientific work of medical researchers working diligently to find one. We can only accomplish our goal with the community's assistance and support of medical research."
"Thalassemia, Love and Needles" is directed by George Carlos of Birmingham, Ala.
"We encourage you to share the documentary with family, friends, and colleagues to help us meet our mission," said Gulas. "We ask you keep the AHEPA Cooley's Anemia Foundation in your mind in the course of your charitable giving
AHEPA headquarters encourages all AHEPA Family chapters to reaffirm their commitment to finding a cure for Cooley's Anemia. Donations to help find a cure for Cooley's Anemia can be made online by visiting www.ahepaonline.com/contribute.aspx.
Jun 11, 2009
Thalassemia and Pregnancy
There is a connection between thalassemia and pregnancy in that the disease is an inherited condition. Parents who either have the disease or are carriers for it can pass thalassemia onto their child. Couples who are concerned about thalassemia and pregnancy can undergo genetic testing or use in vitro fertilization to minimize the chances of having a baby with thalassemia.
Is There a Link Between Thalassemia and Pregnancy?
Thalassemia is a type of inherited blood disorder that can cause anemia. It affects a person's ability to produce hemoglobin, which is the protein in red blood cells that delivers oxygen to all parts of the body.
Approximately 100,000 babies worldwide are born with severe forms of thalassemia each year. However, the condition occurs more frequently in people of Italian, Greek, Middle Eastern, Southern Asian, and African ancestry.
The Thalassemia Gene and Pregnancy
Parents who carry the mutated thalassemia gene can pass the gene on to their children. A child who inherits one mutated gene is considered to be a carrier, also known as thalassemia trait. Most people who have thalassemia trait lead completely normal, healthy lives.
Thalassemia and Pregnancy: What's the Risk?
If two people with beta thalassemia trait (carriers) have a baby, one of three things can happen:
•The baby could receive two normal genes (one from each parent) and have normal blood (1 in 4 chance)
•The baby could receive one normal gene from one parent and one variant gene from the other parent, and have thalassemia trait (2 in 4 chance)
•The baby could receive two thalassemia genes (one from each parent) and have a moderate to severe form of the disease (1 in 4 chance).
Thalassemia and Pregnancy: Genetic Tests
If a women or her spouse has a family history of thalassemia, they may want to consider genetic testing before becoming pregnant. Blood tests and family genetic studies can show whether an individual has thalassemia or is a carrier of thalassemia trait. If both parents are carriers, they may want to consult with a genetic counselor for help in deciding whether to conceive or whether to have a fetus that has tested positive for thalassemia.
Thalassemia and Pregnancy: Prenatal Testing
Prenatal testing for thalassemia can be done when a woman is 11 weeks pregnent using chorionic villi sampling (CVS). CVS involves the removal of a tiny piece of the placenta, which will then be tested. Prenatal testing can also be done with an amniocentesis when a woman is 16 weeks pregnant. In this procedure, a needle is used to take a sample of the fluid surrounding the baby, which will then be tested.
Thalassemia and Pregnancy: Assisted Reproductive Therapy
Assisted reproductive therapy is an option for people who are carriers and who don't want to risk giving birth to a child with thalassemia.
A new technique, pre-implantation genetic diagnosis (PGD), used in conjunction with in vitro fertilization, may enable parents who have thalassemia or who carry the trait to give birth to healthy babies. Embryos created in vitro are tested for the thalassemia gene before being implanted into the mother, allowing only healthy embryos to be selected.
Is There a Link Between Thalassemia and Pregnancy?
Thalassemia is a type of inherited blood disorder that can cause anemia. It affects a person's ability to produce hemoglobin, which is the protein in red blood cells that delivers oxygen to all parts of the body.
Approximately 100,000 babies worldwide are born with severe forms of thalassemia each year. However, the condition occurs more frequently in people of Italian, Greek, Middle Eastern, Southern Asian, and African ancestry.
The Thalassemia Gene and Pregnancy
Parents who carry the mutated thalassemia gene can pass the gene on to their children. A child who inherits one mutated gene is considered to be a carrier, also known as thalassemia trait. Most people who have thalassemia trait lead completely normal, healthy lives.
Thalassemia and Pregnancy: What's the Risk?
If two people with beta thalassemia trait (carriers) have a baby, one of three things can happen:
•The baby could receive two normal genes (one from each parent) and have normal blood (1 in 4 chance)
•The baby could receive one normal gene from one parent and one variant gene from the other parent, and have thalassemia trait (2 in 4 chance)
•The baby could receive two thalassemia genes (one from each parent) and have a moderate to severe form of the disease (1 in 4 chance).
Thalassemia and Pregnancy: Genetic Tests
If a women or her spouse has a family history of thalassemia, they may want to consider genetic testing before becoming pregnant. Blood tests and family genetic studies can show whether an individual has thalassemia or is a carrier of thalassemia trait. If both parents are carriers, they may want to consult with a genetic counselor for help in deciding whether to conceive or whether to have a fetus that has tested positive for thalassemia.
Thalassemia and Pregnancy: Prenatal Testing
Prenatal testing for thalassemia can be done when a woman is 11 weeks pregnent using chorionic villi sampling (CVS). CVS involves the removal of a tiny piece of the placenta, which will then be tested. Prenatal testing can also be done with an amniocentesis when a woman is 16 weeks pregnant. In this procedure, a needle is used to take a sample of the fluid surrounding the baby, which will then be tested.
Thalassemia and Pregnancy: Assisted Reproductive Therapy
Assisted reproductive therapy is an option for people who are carriers and who don't want to risk giving birth to a child with thalassemia.
A new technique, pre-implantation genetic diagnosis (PGD), used in conjunction with in vitro fertilization, may enable parents who have thalassemia or who carry the trait to give birth to healthy babies. Embryos created in vitro are tested for the thalassemia gene before being implanted into the mother, allowing only healthy embryos to be selected.
Jun 1, 2009
Anemia Drugs May Raise Death Risk in Cancer Patients
Latest findings support recent label warnings for Procrit, Aranesp, experts say
By Steven Reinberg, HealthDay Reporter
THURSDAY, April 30 (HealthDay News) -- Two new studies provide more evidence that drugs such as Procrit and Aranesp, often used by cancer patients to fight anemia-linked fatigue, may boost the risk of death and serious adverse events such as blood clots.
These drugs, called erythropoiesis-stimulating agents (ESAs), have also been associated in prior studies with increased risk of heart attack, stroke and tumor growth. The primary argument for the continued use of these drugs is that they help reduce the number of blood transfusions some cancer patients need, while improving quality of life.
However, a co-author of one paper, Dr. Anthony Reiman, from the University of Alberta, Canada, said his team is "supporting other groups that are recommending great caution in using these drugs for cancer patients, and in routine circumstances they may not be indicated. We hope the drugs would still be made available for people for whom transfusion isn't a good option -- but those are very limited circumstances."
ESAs include erythropoietin (Epogen, Procrit) and darbepoetin (Aranesp). They work by stimulating the bone marrow to produce new red blood cells, according to the U.S. National Institutes of Health. They are used to treat anemia caused by chemotherapy and to treat anemia in people with chronic kidney disease who are on dialysis.
But rising concern led the U.S. Food and Drug Administration in 2007 to ask the drugs' manufacturers to add a "black box" warning to the medications. The warning indicates that the medications should be used at the lowest possible doses to avoid risks such as blood clots, heart attacks, stroke, congestive heart failure, increased tumor growth and an increased risk of death. The FDA also recommended that the medications be prescribed at the lowest doses possible because trials generally indicated an increased risk when blood levels were raised above 12 grams per deciliter.
The two new studies may buttress that move. In the first study, Reiman and other researchers analyzed data from 52 clinical trials that included more than 12,000 people.
The result: "The use of drugs to encourage red blood cell formation in cancer patients with anemia increases the risk of death and serious adverse events such as blood clots," according to co-researcher Dr. Scott Klarenbach, an assistant professor at the University of Alberta.
Although risk of death was only 15 percent to 16 percent higher among patients who used the drugs than those who did not, the high death rates among cancer patients means this increase could affect a significant number of people, the researchers say.
"These medications should not routinely be used as an alternative to blood transfusions in patients with anemia related to cancer, unless future studies demonstrate safety and clinical benefits," Klarenbach said. "While use of medications [instead of blood transfusion] may be appealing to both patients and practitioners, their use is associated with an increased risk of death."
"At best, these drugs don't seem to improve longevity," Reiman said. "They may have some benefits in improving quality of life."
The report is published in the April 30 online edition of the Canadian Medical Association Journal.
In another report, in the May 2 issue of The Lancet, researchers led by Dr. Julia Bohlius, from the University of Bern in Switzerland, looked at the findings from 53 cancer trials that included a total of almost 14,000 patients. More than 1,500 patients died during the study period, and almost 5,000 patients died overall.
The researchers found that ESAs were associated with a 17 percent increase in deaths during the study period. Among patients receiving chemotherapy, ESAs increased the death risk by 10 percent, they report.
The findings "show that erythropoiesis-stimulating agents increase mortality in all patients with cancer, and a similar increase might exist in patients on chemotherapy," the authors wrote. "In clinical practice, the increased risks of death and thromboembolic events should be balanced against the benefits of treatment with erythropoiesis-stimulating agents, taking into account each patient's clinical circumstances and preferences. More data are needed for the effect of these drugs on quality of life and tumor progression, and meta-analyses similar to this one will address these questions," they added.
Dr. Charles Bennett, the A.C. Beuhler professor of geriatric medicine at the Feinberg School of Medicine at Northwestern University, helped conduct a study, published in the Journal of the American Medical Association early last year, that also found similar risks for the use of ESAs by cancer patients. He believes the new data support those findings.
"The message is clear: There is a safety concern that's real and significant," Bennett said.
In addition, Bennett believes that quality-of-life issues and the need for a reduction in blood transfusions for cancer patients are overstated. "The [appropriate] use of these drugs in the United States is for palliative care in cancer patients and I support that," he said.
By Steven Reinberg, HealthDay Reporter
THURSDAY, April 30 (HealthDay News) -- Two new studies provide more evidence that drugs such as Procrit and Aranesp, often used by cancer patients to fight anemia-linked fatigue, may boost the risk of death and serious adverse events such as blood clots.
These drugs, called erythropoiesis-stimulating agents (ESAs), have also been associated in prior studies with increased risk of heart attack, stroke and tumor growth. The primary argument for the continued use of these drugs is that they help reduce the number of blood transfusions some cancer patients need, while improving quality of life.
However, a co-author of one paper, Dr. Anthony Reiman, from the University of Alberta, Canada, said his team is "supporting other groups that are recommending great caution in using these drugs for cancer patients, and in routine circumstances they may not be indicated. We hope the drugs would still be made available for people for whom transfusion isn't a good option -- but those are very limited circumstances."
ESAs include erythropoietin (Epogen, Procrit) and darbepoetin (Aranesp). They work by stimulating the bone marrow to produce new red blood cells, according to the U.S. National Institutes of Health. They are used to treat anemia caused by chemotherapy and to treat anemia in people with chronic kidney disease who are on dialysis.
But rising concern led the U.S. Food and Drug Administration in 2007 to ask the drugs' manufacturers to add a "black box" warning to the medications. The warning indicates that the medications should be used at the lowest possible doses to avoid risks such as blood clots, heart attacks, stroke, congestive heart failure, increased tumor growth and an increased risk of death. The FDA also recommended that the medications be prescribed at the lowest doses possible because trials generally indicated an increased risk when blood levels were raised above 12 grams per deciliter.
The two new studies may buttress that move. In the first study, Reiman and other researchers analyzed data from 52 clinical trials that included more than 12,000 people.
The result: "The use of drugs to encourage red blood cell formation in cancer patients with anemia increases the risk of death and serious adverse events such as blood clots," according to co-researcher Dr. Scott Klarenbach, an assistant professor at the University of Alberta.
Although risk of death was only 15 percent to 16 percent higher among patients who used the drugs than those who did not, the high death rates among cancer patients means this increase could affect a significant number of people, the researchers say.
"These medications should not routinely be used as an alternative to blood transfusions in patients with anemia related to cancer, unless future studies demonstrate safety and clinical benefits," Klarenbach said. "While use of medications [instead of blood transfusion] may be appealing to both patients and practitioners, their use is associated with an increased risk of death."
"At best, these drugs don't seem to improve longevity," Reiman said. "They may have some benefits in improving quality of life."
The report is published in the April 30 online edition of the Canadian Medical Association Journal.
In another report, in the May 2 issue of The Lancet, researchers led by Dr. Julia Bohlius, from the University of Bern in Switzerland, looked at the findings from 53 cancer trials that included a total of almost 14,000 patients. More than 1,500 patients died during the study period, and almost 5,000 patients died overall.
The researchers found that ESAs were associated with a 17 percent increase in deaths during the study period. Among patients receiving chemotherapy, ESAs increased the death risk by 10 percent, they report.
The findings "show that erythropoiesis-stimulating agents increase mortality in all patients with cancer, and a similar increase might exist in patients on chemotherapy," the authors wrote. "In clinical practice, the increased risks of death and thromboembolic events should be balanced against the benefits of treatment with erythropoiesis-stimulating agents, taking into account each patient's clinical circumstances and preferences. More data are needed for the effect of these drugs on quality of life and tumor progression, and meta-analyses similar to this one will address these questions," they added.
Dr. Charles Bennett, the A.C. Beuhler professor of geriatric medicine at the Feinberg School of Medicine at Northwestern University, helped conduct a study, published in the Journal of the American Medical Association early last year, that also found similar risks for the use of ESAs by cancer patients. He believes the new data support those findings.
"The message is clear: There is a safety concern that's real and significant," Bennett said.
In addition, Bennett believes that quality-of-life issues and the need for a reduction in blood transfusions for cancer patients are overstated. "The [appropriate] use of these drugs in the United States is for palliative care in cancer patients and I support that," he said.
May 28, 2009
Recent studies suggest that using umbilical cord blood from a newborn sibling may be as effective as a bone marrow transplant
Is there a cure for thalassemia?
Some children with thalassemia can be cured with a bone marrow transplant. However, this form of treatment is most successful when a donor who is an exact genetic match is available. Generally, a sibling or other family member is most likely to be an exact match. The procedure can cure about 85 percent of children who have a fully matched family donor 9(). However, only about 30 percent of children with thalassemia have a family member who is a suitable donor (4). The procedure is risky and can result in death.
Recent studies suggest that using umbilical cord blood from a newborn sibling may be as effective as a bone marrow transplant (9). Like bone marrow, cord blood contains unspecialized cells called stem cells that produce all other blood cell.
What research on thalassemia is being done?
Scientists are working on better ways to remove excess iron from the body to prevent or delay iron overload. They are developing and testing new oral iron-chelating drugs and looking at whether combining one of these drugs with deferoxamine may be more effective than either treatment alone (1, 2).
Researchers are studying the effectiveness of certain drugs (including hydroxyurea, a drug used to treat sickle cell disease) in reactivating the genes for fetal hemoglobin. All humans produce a fetal form of hemoglobin before birth. After birth, natural genetic switches "turn off" production of fetal hemoglobin and "turn on" production of adult hemoglobin. Scientists are seeking ways to activate these genetic switches so that they can make the blood cells of individuals with beta thalassemia produce more fetal hemoglobin to make up for their deficiency of adult hemoglobin. Studies to date suggest that treatment with these drugs may be helpful for some patients with beta thalassemia intermedia (2).
Researchers also are exploring the possibility that dietary treatments, such as with vitamin E, may help reduce organ damage from iron buildup (1, 6). Others continue to improve bone marrow transplantation methods that may offer a cure to more children with thalassemia.
March of Dimes grantees have been among the many scientists seeking to develop an effective form of gene therapy that may offer a cure for thalassemia. Gene therapy may involve inserting a normal alpha or beta globin gene into the patient’s stem cells, possibly allowing these immature blood cells to produce normal red blood cells.
Some children with thalassemia can be cured with a bone marrow transplant. However, this form of treatment is most successful when a donor who is an exact genetic match is available. Generally, a sibling or other family member is most likely to be an exact match. The procedure can cure about 85 percent of children who have a fully matched family donor 9(). However, only about 30 percent of children with thalassemia have a family member who is a suitable donor (4). The procedure is risky and can result in death.
Recent studies suggest that using umbilical cord blood from a newborn sibling may be as effective as a bone marrow transplant (9). Like bone marrow, cord blood contains unspecialized cells called stem cells that produce all other blood cell.
What research on thalassemia is being done?
Scientists are working on better ways to remove excess iron from the body to prevent or delay iron overload. They are developing and testing new oral iron-chelating drugs and looking at whether combining one of these drugs with deferoxamine may be more effective than either treatment alone (1, 2).
Researchers are studying the effectiveness of certain drugs (including hydroxyurea, a drug used to treat sickle cell disease) in reactivating the genes for fetal hemoglobin. All humans produce a fetal form of hemoglobin before birth. After birth, natural genetic switches "turn off" production of fetal hemoglobin and "turn on" production of adult hemoglobin. Scientists are seeking ways to activate these genetic switches so that they can make the blood cells of individuals with beta thalassemia produce more fetal hemoglobin to make up for their deficiency of adult hemoglobin. Studies to date suggest that treatment with these drugs may be helpful for some patients with beta thalassemia intermedia (2).
Researchers also are exploring the possibility that dietary treatments, such as with vitamin E, may help reduce organ damage from iron buildup (1, 6). Others continue to improve bone marrow transplantation methods that may offer a cure to more children with thalassemia.
March of Dimes grantees have been among the many scientists seeking to develop an effective form of gene therapy that may offer a cure for thalassemia. Gene therapy may involve inserting a normal alpha or beta globin gene into the patient’s stem cells, possibly allowing these immature blood cells to produce normal red blood cells.
May 27, 2009
Radiofrequency ablation of the spleen in patients with thalassemia intermedia: a pilot study.
Research article summary (published 29 Apr 2009):
OBJECTIVE:
We investigated the efficacy and safety of radiofrequency ablation on the hematologic parameters in patients with thalassemia intermedia (TI).
MATERIALS AND METHODS:
Radiofrequency ablation of the spleen was performed in 15 children with TI under general anesthesia using a cool-tip radiofrequency probe. These patients were regarded as the radiofrequency ablation group. Nine patients with TI who underwent partial splenectomy during the past 3 years and another 14 patients with TI who underwent total splenectomy were also enrolled in this study as the first and second control groups (CG1 and CG2).
RESULTS:
In the radiofrequency ablation group, two (13%) patients showed a significant increase in the mean hemoglobin level compared with the year before (1.5 and 1.8 g/dL). In addition, three (20%) other patients became transfusion-free in the year after radiofrequency ablation. In CG1, one (11%) patient showed a significant increase in hemoglobin the year after partial splenectomy, and another two (22%) patients became transfusion-free. In CG2, six (43%) patients revealed a significant increase in hemoglobin in the year after total splenectomy, and another four (29%) revealed a significant decrease in the need for transfusions. The mean increase in hemoglobin and platelet count was more significant in CG2 than in the radiofrequency ablation group and CG1. The mean hospital stay was significantly shorter in the radiofrequency ablation group (1.7 days vs 7.5 and 8.2 days in CG1 and CG2, respectively).
CONCLUSION:
We believe that radiofrequency ablation of the spleen can be a safe procedure in patients with TI and is at least as effective as partial splenectomy, having only minor self-limiting complications.
OBJECTIVE:
We investigated the efficacy and safety of radiofrequency ablation on the hematologic parameters in patients with thalassemia intermedia (TI).
MATERIALS AND METHODS:
Radiofrequency ablation of the spleen was performed in 15 children with TI under general anesthesia using a cool-tip radiofrequency probe. These patients were regarded as the radiofrequency ablation group. Nine patients with TI who underwent partial splenectomy during the past 3 years and another 14 patients with TI who underwent total splenectomy were also enrolled in this study as the first and second control groups (CG1 and CG2).
RESULTS:
In the radiofrequency ablation group, two (13%) patients showed a significant increase in the mean hemoglobin level compared with the year before (1.5 and 1.8 g/dL). In addition, three (20%) other patients became transfusion-free in the year after radiofrequency ablation. In CG1, one (11%) patient showed a significant increase in hemoglobin the year after partial splenectomy, and another two (22%) patients became transfusion-free. In CG2, six (43%) patients revealed a significant increase in hemoglobin in the year after total splenectomy, and another four (29%) revealed a significant decrease in the need for transfusions. The mean increase in hemoglobin and platelet count was more significant in CG2 than in the radiofrequency ablation group and CG1. The mean hospital stay was significantly shorter in the radiofrequency ablation group (1.7 days vs 7.5 and 8.2 days in CG1 and CG2, respectively).
CONCLUSION:
We believe that radiofrequency ablation of the spleen can be a safe procedure in patients with TI and is at least as effective as partial splenectomy, having only minor self-limiting complications.
Subscribe to:
Posts (Atom)