Developing first comprehensive guidelines for management of sickle cell disease

The National Heart, Lung, and Blood Institute has released the first comprehensive, evidence-based guidelines for management of sickle cell disease from birth to end of life. Sickle cell anemia is the most common form of sickle cell disease, a serious disorder in which the body makes sickle-shaped red blood cells.

 

Shirley Miller with Dr. George Buchanan, Professor of Pediatrics and Internal Medicine, holder of the Children's Cancer Fund Distinguished Chair in Pediatric Oncology & Hematology.

 The National Heart, Lung, and Blood Institute (NHLBI) has released the first comprehensive, evidence-based guidelines for management of sickle cell disease from birth to end of life, based on recommendations developed by a nationwide team of experts co-chaired by a UT Southwestern Medical Center hematologist.

 Appearing today in JAMA, the guidelines are intended for general use by pediatricians, physicians treating adults, hematologists, emergency room personnel, hospitalists, and other health care providers. The new management guidelines consist of more than 500 specific directions for physicians who are caring for patients with sickle cell disease.

"The aim is to improve the care of all people with sickle cell disease, young and old, and to raise awareness among the entire medical profession regarding the need for better care and more research, so that someday everyone with sickle cell disease can receive the best possible care and lead a normal and productive life," said Dr. George Buchanan, Professor of Pediatrics and Internal Medicine.

Although currently most patients are diagnosed at birth and survive until adulthood, many sickle cell disease patients die in their 30s and 40s of acute complications or chronic organ damage. Dr. Buchanan and the team of expert panelists want to alter that statistic through improved and comprehensive treatment.

One survivor who beat those numbers is 58-year-old Shirley Miller, who worked at UT Southwestern with Dr. Buchanan from 2002 to 2010 as a program manager, patient advocate, and outreach coordinator.

"I lived my life in fear because I thought age 30 was it. I wasted a lot of time wondering how the end would happen. My parents never told me my life expectancy; I went to the library and looked it up," said Ms. Miller, who is now helping to launch a comprehensive sickle cell adult program in Charlotte, North Carolina.

Diagnosed at age three, and the only one of five siblings with the disease, she grew up without physical education classes and did not participate in sports. She made friends slowly and was embarrassed when others went through puberty before her. She credits her parents with helping her believe she could make it, and she credits the care she later received as an adult at UT Southwestern.

"Comprehensive care is the key to successful management of sickle cell disease, known as sickle cell disease. Currently, there are not enough physicians who specialize in the care of adults with sickle cell disease, which means that many are seen by primary care physicians or other specialists," said Ms. Miller. "These guidelines will provide physicians with a tool for basic understanding of the disease etiology and possible complications to look for when managing a patient. I attribute my survival to the comprehensive care that I received from this teaching and research university, which is on the cutting edge of so many developments. The knowledge and expertise available here have made all the difference."

The expert panel for the new guidelines is a 12-member team, all known for their experience in diagnosing and treating people with sickle cell disease. Panel members included two pediatric hematologists, four adult hematologists, an obstetrician, a psychiatrist, an emergency department nurse, two blood transfusion specialists, and one family physician. These experts were supported by a large staff of NHLBI leaders and other personnel, including experts in finding and analyzing the available scientific evidence that could help improve the lives of people with sickle cell disease.
Sickle cell disease is the world's most common serious condition due to a single gene mutation. An estimated 70,000 to 100,000 people in the U.S. have sickle cell disease. Of these, about 1,000 receive care annually at UT Southwestern. Dr. Buchanan has led the institutional pediatric and research sickle cell disease programs for 37 years.

More than 2 million Americans carry the sickle cell trait.
"African-Americans are far more likely than Caucasians to have the sickle cell trait, which is not a disease but a carrier state. One has to receive a copy of the abnormal gene from both parents to have the disease," said Dr. Buchanan, who holds the Children's Cancer Fund Distinguished Chair in Pediatric Oncology & Hematology.
"Every state now has mandatory newborn screening for the disease," said Dr. Buchanan, Director of the Barrett Family Center for Pediatric Oncology at UT Southwestern.
Dr. Buchanan was instrumental in ensuring that Texas became the third state to adopt newborn screening in 1983. Approximately 150 infants with sickle cell disease are diagnosed in Texas each year. Nearly one third of them receive their care at Children's Medical Center in Dallas.

When sickle cell disease progresses, it can delay puberty and cause acute and chronic complications, including debilitating pain, life-threatening infections, damage to vital organs, and stroke. Stem cell transplants offer a potential cure; however, the high cost, lack of suitable donors (ideally the donor is a sibling), and the risk of complications make these transplants relatively infrequent. The newly published comprehensive guidelines recommend better pain control; prevention and treatment of acute and chronic complications; general health maintenance; judicious use of blood transfusions; and teaching patients to manage their disease through behavioral changes.

The committee also strongly advocates for prescribing hydroxyurea, an oral medication taken once daily that has become the standard of care. Hydroxyurea reduces the impact of the disease by improving the anemia, and reducing the risk of pain events and acute chest syndrome. It can also decrease the need for transfusions and hospital admissions.
"These national guidelines are directed not just to hematologists but to all medical practitioners who might encounter sickle cell disease patients, to inform them about hydroxyurea and how to best offer general medical care to them," Dr. Buchanan said. "We have a lot of work to do to educate physicians."

September is National Sickle Cell Awareness Month, and the guidelines will be discussed and disseminated at professional conferences, as well as being available on the NHLBI website and in JAMA, the journal of the American Medical Association.
According to NHLBI, sickle cell anemia is the most common form of sickle cell disease, a serious disorder in which the body makes sickle-shaped red blood cells. "Sickle-shaped" means that the red blood cells are shaped like a crescent. Normal red blood cells are disc-shaped and look like doughnuts without holes in the center, moving easily through blood vessels. Red blood cells contain an iron-rich protein called hemoglobin, which carries oxygen from the lungs to the rest of the body. Sickle cells contain abnormal hemoglobin called sickle hemoglobin or hemoglobin S. They tend to block blood flow in the blood vessels of the limbs and organs, causing pain, organ damage, and increased risk for infection. In the U.S., the disease occurs in about one out of every 500 African-American births and in more than one out of every 36,000 Hispanic-American births.

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New Guidelines for Sickle Cell Disease

An expert panel has issued new guidelines for managing sickle cell disease, stressing the use of the drug hydroxyurea and transfusions for many with the genetic disorder.

By Kathleen Doheny
HealthDay Reporter

 “This is a major step forward to try to put together all of the evidence and try to highlight what is most important,” said Dr. Barbara Yawn, professor of family and community health at Olmsted Medical Center in Rochester, Minn. Yawn was also co-chair of the panel convened by the U.S. National Heart, Lung, and Blood Institute to develop the new guidelines.

As many as 100,000 Americans have sickle cell disease, according to background information with the guidelines. In sickle cell disease, the body makes sickle-shaped or crescent-shaped red blood cells. Normal red blood cells are disc-shaped, like a doughnut without holes, allowing the cells to move easily through blood vessels.

Sickle cells are stiff and sticky and tend to block blood flow, leading to organ damage, pain and increased risk of infection and strokes, among other problems. Black people are more commonly affected than other people.

The expert panel reviewed more than 12,000 scientific articles and sifted through the evidence to issue the new blueprint for care. The new guidelines are published Sept. 10 in the Journal of the American Medical Association.

One of the new recommendations is to give children oral penicillin daily until age 5. This is a preventive measure, aiming to reduce the risk of pneumonia and other infections.

“That has been the standard for a while now,” Yawn said. “Now we are saying ‘This is an absolute necessity.'”

In addition, everyone with sickle cell disease should be vaccinated against pneumonia, according to the guidelines. “The children need pneumococcal vaccine as early as they can possibly get it, around six weeks of age,” Yawn said.

Children from ages 2 to 16 should have an annual exam known as a transcranial Doppler, which measures blood flow in the brain, the guidelines explain. If it’s abnormal, long-term transfusion therapy to prevent stroke is recommended. 

When acute complications occur, opioids (also known as narcotics) are suggested to treat the pain linked with blood flow blockage. A method of encouraging deep breathing — incentive spirometry — is also advised for those hospitalized with a blood flow crisis.

If adults have three or more severe blood flow crises in a year, treatment with the drug hydroxyurea is recommended. The drug works in sickle cell by helping to prevent the formation of sickle-shaped red blood cells. Hydroxyurea can be used in infants, children and teens, whether or not they currently have symptoms, according to the guidelines.

One difficulty in developing the guidelines, Yawn said, is that there is “not enough research to answer all the questions.”

People with sickle cell disease are living longer, she said. A generation ago, many with sickle cell disease only survived until their 20s or 30s. “We know there are more living into their 40s, 50s and 60s,” she said.

Dr. Michael DeBaun, professor of pediatrics and medicine at the Vanderbilt University School of Medicine, said, “These are really strong recommendations.”

DeBaun wrote an editorial to accompany the guideline report. “This should now be a road map of how your child should be cared for,” he said.

The information also applies for adults with sickle cell disease, said DeBaun, who is also director of the Vanderbilt–Meharry Sickle Cell Disease Center of Excellence.

He advises patients and parents to use the new guidelines to have a dialogue with the doctors providing care. “We expect these recommendations to change over time as more evidence becomes available,” DeBaun said.

In his own recent study, published in August in the New England Journal of Medicine, DeBaun and his colleagues reported that monthly blood transfusions appear to reduce the risk of strokes in children with sickle cell anemia, the most common form of sickle cell disease.

More information

To learn more about sickle cell disease, visit the U.S. Centers for Disease Control and Prevention.

6 causes of anemia during pregnancy

Gestational anemia or anemia during pregnancy is one condition that can affect a woman at any time during her pregnancy.

While planning your pregnancy, you need to make sure that your health is at its optimum. This includes your blood count, fitness and management of various lifestyle related ailments. All this will ensure a smooth pregnancy and good health of both the mother and the child growing inside the womb. However, those nine months of pregnancy aren’t predictable, and health complications can arise at any time. Gestational anemia or anemia during pregnancy is one such condition that can affect a woman at any time during her pregnancy.

Here are a few causes that could lead to the same:

Deficiency of iron
Iron deficiency during pregnancy is a common cause of gestational anemia. This happens when the body is unable to produce enough iron to produce adequate hemoglobin. Hemoglobin is a protein that is present in the red blood cells. During pregnancy the blood supply in the body almost doubles up to meet the requirements of the mother and that of the growing baby. The hemoglobin in the blood is responsible for nutrient and oxygen exchange between a mother and the baby. It is also responsible for oxygen circulation in the mother to restore health during pregnancy. During pregnancy the iron requirement for a woman increases and one might need around 30 to 38 mg of iron either through dietary sources or by having iron supplements regularly. Here are reasons why you need to be regular with iron medications during pregnancy.

Deficiency of folic acid
Everyone knows the importance of folic acid during pregnancy. It is a type of B vitamin that helps produce new cells including healthy red blood cells. Therefore, during pregnancy a woman needs more folate. It is recommended that women take at least 400 mg of folate during pregnancy to avoid birth defects in babies. Folate or folic acid deficiency can lead to less production of red blood cells that could hamper oxygen and nutrient supply to the fetus and result in severe birth defects like neural tube abnormalities or spina bifida and lead to low birth weight of the baby. This kind of anemia can be easily corrected by taking folic acid pills or through proper diet management. Here are reasons why you need folic acid during pregnancy. 

Vitamin B 12 deficiency
Vitamin B 12 is an important vitamin for pregnant women that plays a major role in producing healthy red blood cells. Lack of Vitamin B 12 in the diet could give rise to the gestational anemia that could contribute to birth defects, such as neural tube abnormalities, and lead to preterm labor. Women who don’t eat meat, poultry, dairy products, and eggs have a greater risk of developing vitamin B12 deficiency. Here are other seven diet essentials you should take during pregnancy.  

Having twins
Mothers who are carrying twins or triplets need special care to meet the demands of their growing babies. Improper diet and ignorance of medications can lead to various health complications and gestational anemia could be one of them. Women with twins or triplets are always at risk of developing complications during pregnancy.

Improper diet
Gestational anemia as mentioned above could be easily avoided with proper diet management and being regular with medications. Irregularities in diet especially failing to get enough iron, folate and vitamin B 12 could lead to the gestational anemia in women. Know more about the causes, symptoms and treatment of anemia during pregnancy.

Being anemic before conception
If you were anemic or had lower hemoglobin count prior to conception you could be at a risk of developing gestational anemia. Even with adequate hemoglobin count during the start of pregnancy it is possible to suffer from gestational anemia. This happens due to altered body mechanism and the various hormonal changes. It is imperative to check with your doctor about medications and management of anemia during pregnancy, especially if you had suffered from the same before.

Educational Webcast on Beta-thalassemia

An online seminar lead by Prominent hematology expert, Ellis Neufeld, M.D., Ph.D.

Acceleron Pharma Inc. (NASDAQ:XLRN), a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of novel protein therapeutics for cancer and rare diseases,hosted an educational webcast seminar on beta-thalassemia with Ellis Neufeld, M.D., Ph.D on 17.10.2014. Acceleron and its collaboration partner, Celgene, are conducting phase 2 clinical trials of sotatercept and luspatercept in patients with beta-thalassemia, MDS, and end-stage renal disease with mineral and bone disorder.

Dr. Neufeld currently serves as Associate Chief of the Hematology/Oncology Division and Co-Chief of the Clinical Research Center at Boston Children’s Hospital, Director of the Boston Hemophilia Center, and is the Egan Family Foundation Professor of Pediatrics at Harvard Medical School.

Dr. Neufeld provided an overview of beta-thalassemia including the numerous clinical complications of the disease, current treatment and a review of the recently presented data from the sotatercept and luspatercept phase 2 studies in beta-thalassemia.

 To access the recorded webcast, please visit the "Events & Presentations" page in the Investors & Media section on the Company's website (http://investor.acceleronpharma.com/events.cfm).

First Patient with Sickle Cell Disease Transplanted with LentiGlobin Gene Therapy

bluebird bio Announces First Patient with Sickle Cell Disease Transplanted with LentiGlobin Gene Therapy

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Oct. 14, 2014-- bluebird bio, Inc. (Nasdaq: BLUE) a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic and orphan diseases, today announced that the first subject with severe sickle cell disease has undergone infusion with bluebird bio’s LentiGlobin BB305 drug product in an autologous hematopoietic stem cell transplantation. This patient is enrolled in the HGB-205 Study being conducted in Paris, France. bluebird has also opened a separate US-based trial (HGB-206) in the United States for the treatment of up to 8 severe sickle cell disease patients with the company’s LentiGlobin BB305 drug product.

“We are treating a sickle cell patient for the first time with gene therapy,” stated Marina Cavazzana, MD, PhD, Professor of Medicine at Paris Descartes University and Research Director at the Centre for Clinical Research in Biotherapy, Necker Hospital, and at the Institute of Genetic Diseases, Imagine, Paris France. “Sickle cell disease is a devastating disease that affects hundreds of thousands of people in the US and Europe and millions around the world. The therapeutic options for patients with sickle cell disease are currently limited, so the opportunity to bring a one-time, potentially curative treatment to these patients by modification of autologous hematopoietic stem cells would represent a great advance for patients with sickle cell disease and for the field.”
“Sickle cell disease shortens life expectancy by decades even in developed countries, so it is exciting to contemplate that LentiGlobin may offer the curative potential of allogeneic stem cell transplantation by using a patient’s own cells,” stated David Davidson, MD, bluebird bio’s Chief Medical Officer. “In June 2014, we reported preliminary results from the HGB-205 Study demonstrating that treatment with LentiGlobin drug product led to high-level production of beta-T87Q-globin and rapid transfusion independence in two beta-thalassemia major patients. Given the anti-sickling property of the amino acid substitution engineered into beta-T87Q-globin, we are optimistic about the potential for LentiGlobin to mitigate the signs and symptoms of sickle cell disease. We anticipate providing initial clinical data on LentiGlobin in sickle cell disease patients in 2015.”

About the HGB-205 Study
The phase 1/2 study is designed to evaluate the safety and efficacy of LentiGlobin BB305 drug product in the treatment of subjects with beta-thalassemia major and severe sickle cell disease. The study is designed to enroll up to seven subjects. Subjects will be followed to evaluate safety and transfusion requirements post-transplant. In sickle cell disease patients, efficacy will also be measured based on the frequency of vaso-occlusive crises or acute chest syndrome events.
For more information on the HGB-205 Study, please visit www.clinicaltrials.gov using identifier NCT02151526.

About the HGB-206 Study
The phase 1 study is designed to evaluate the safety and efficacy of LentiGlobin BB305 drug product in the treatment of subjects with severe sickle cell disease. The study is designed to enroll up to eight subjects. Subjects will be followed to evaluate safety and efficacy will be measured based on changes in red cell function tests, hemolysis markers and frequency of clinical events secondary to sickle cell disease (e.g. vaso-occlusive crises or acute chest syndrome events).
For more information on the HGB-206 Study, please visit www.clinicaltrials.gov using identifier NCT02140554.

About sickle cell disease
Sickle cell disease (SCD) is a hereditary blood disorder resulting from a mutation in the beta globin gene that causes polymerization of hemoglobin proteins and abnormal red blood cell function. The symptoms of SCD include anemia, vaso-occlusive crises and strokes. The global incidence of SCD is estimated to be 250,000 to 300,000 births annually, and the global prevalence of the disease is estimated to be about 20 to 25 million.

About bluebird bio, Inc.
bluebird bio is a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic and orphan diseases. bluebird bio has two clinical-stage programs in development. The most advanced product candidate, Lenti-D, is in a recently-initiated phase 2/3 study, the Starbeam Study, for the treatment of childhood cerebral adrenoleukodystrophy (CCALD), a rare, hereditary neurological disorder affecting young boys. The next most advanced product candidate, LentiGlobin, is currently in two phase 1/2 studies, one in the US (the Northstar Study) and one in France (HGB-205), for the treatment of beta-thalassemia major. The phase 1/2 HGB-205 study also allows enrollment of patient(s) with sickle cell disease, and bluebird bio is conducting a separate U.S. sickle cell disease trial (HGB-206).

bluebird bio also has an early-stage chimeric antigen receptor-modified T cell (CAR-T) program for oncology in collaboration with Celgene Corporation.
bluebird bio has operations in Cambridge, Massachusetts, Seattle, Washington, and Paris, France. For more information, please visit www.bluebirdbio.com .

Iron supplements improve anemia, quality of life for women with heavy periods

A study by researchers from Finland found that diagnosis and treatment of anemia is important to improve quality of life among women with heavy periods. Findings published in Acta Obstetricia et Gynecologica Scandinavica, a journal of the Nordic Federation of Societies of Obstetrics and Gynecology, suggest clinicians screen for anemia and recommend iron supplementation to women with heavy menstrual bleeding (menorrhagia).

 One of the common causes of iron deficiency and anemia is heavy bleeding during menstration. Over time monthly mentrual iron loss without adequate dietary iron supplementation can reduce iron stores in the body. Previous studies have found that iron deficiency anemia may impact women's physical performance, cognitive function, mood, and overall quality of life.

Led by Dr. Pirkko Peuranpää from the Department of Obstetrics and Gynecology at Hyvinkää Hospital in Finland, this prospective study assessed the impact of anemia and iron deficiency on health-related quality of life in 236 women treated for heavy menstrual bleeding. The participants were randomized to either hysterectomy or treatment with a levonorgestrel-releasing intrauterine system such as Mirena®.

The team separated the participants into two groups. Women with hemoglobin -- the oxygen-carrying proteins in the red blood cells -- levels less than 120 g/L were defined as anemic and those with levels greater than 120 g/L were in the non-anemic group. Researchers also measured levels of ferritin in the blood to assess iron stores in both groups.

Results show that at the start of the study, 27% of women were anemic and 60% were severely iron deficient with ferritin levels less than 15 µg/L. In those women who were anemic only 8% took an iron supplement. One year following treatment hemoglobin levels had increased in both groups, but women who were initially anemic still had significantly lower levels compared to those in the non-anemic group.

One year after treatment women in the anemic group had a significant increase in energy, along with physical and social function, and a decrease in anxiety and depression compared to the non-anemic group. It took five years for the iron stores to reach normal levels. "The quality of life of women with heavy periods is plural, but the treatment of anemia is important to get good results," concludes Dr. Peuranpää. "Our findings suggest that clinicians should screen for anemia in women with heavy menstrual bleeding and recommend early iron supplementation as part of the treatment process."

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Acetate supplements speed up red blood cell production, anemia research shows

UT Southwestern Medical Center researchers seeking novel treatments for anemia found that giving acetate, the major component of household vinegar, to anemic mice stimulated the formation of new red blood cells.

 Currently, the hormone erythropoietin is administered to treat anemia, but this treatment carries with it side effects such as hypertension and thrombosis (blood clotting). The new research, which was performed in mice, suggests that acetate supplements could eventually be a suitable supplement or possibly even an alternative to administration of erythropoietin.

"Using rational interventions based on the mechanistic insights gleaned from our current studies, we may be able to treat acutely or chronically anemic patients with acetate supplements and thereby reduce the need for blood transfusions or erythropoietin therapy," said Dr. Joseph Garcia, Associate Professor of Internal Medicine at UT Southwestern, staff physician-scientist at the VA North Texas Health Care System, and senior author of the study, published in Nature Medicine.

Anemia is the most common blood disorder, affecting some 3.5 million people, including children and women of child-bearing age, as well as many elderly persons. It can have a significant impact on quality of life, leading to fatigue, weakness, and decreased immune function. People who are anemic produce insufficient red blood cells, which deliver oxygen to tissues throughout the body.

UT Southwestern researchers began their studies by identifying a critical pathway that controls the production of red blood cells in conditions of stress, such as low oxygen. Using genetically modified mice, researchers observed that low oxygen, a state known as hypoxia, stimulates the production of acetate.

Acetate, in turn, activates a molecular pathway that ultimately results in the production of red blood cells, or erythropoiesis, by triggering the production of the protein that stimulates this process, called erythropoietin.

"Our study shows that acetate functions as a biochemical 'flare,' linking changes in cell metabolism that occur during hypoxia with the activation of a selective stress signaling pathway," Dr. Garcia said.

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Gene mutation discovered in blood disorder aplastic anemia

An international team of scientists has identified a gene mutation that causes aplastic anemia, a serious blood disorder in which the bone marrow fails to produce normal amounts of blood cells. Studying a family in which three generations had blood disorders, the researchers discovered a defect in a gene that regulates telomeres, chromosomal structures with crucial roles in normal cell function.

 "Identifying this causal defect may help suggest future molecular-based treatments that bypass the gene defect and restore blood cell production," said study co-leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia (CHOP).

Hakonarson and CHOP colleagues collaborated with Australian scientists on the study, published online Sept. 9 in the journal Blood.

"We're thrilled by this discovery which has advanced our understanding of certain gene mutations and the causal relationship to specific diseases," said study co-leader Tracy Bryan, Ph.D., Unit Head of the Cell Biology Unit at the Children's Medical Research Institute in Westmead, New South Wales, Australia.
The research team studied an Australian family with aplastic anemia and other blood disorders, including leukemia. Hakonarson and lead analyst Yiran Guo, Ph.D., along with genomics experts from BGI-Shenzhen, performed whole-exome sequencing on DNA from the families and identified an inherited mutation on the ACD gene, which codes for the telomere-binding protein TPP1.

Telomeres, complex structures made of DNA and protein, are located on the end of chromosomes, where they protect the chromosomes' stability. They are sometimes compared to plastic tips at the end of shoelaces that prevent the laces from fraying.

Telomeres shorten after each cell division, and gradually lose their protective function. Aging cells, with their shortened telomeres, become progressively more vulnerable to DNA damage and cell death. Separately from the aging process, certain inherited and acquired disorders may shorten telomeres and injure rapidly dividing blood-forming cells produced in bone marrow. This leads to bone marrow failure, one example of which is aplastic anemia.

Bryan's team investigated the function of the ACD gene. They determined that the mutation shortened telomeres and interrupted the ability of telomeres to attract the enzyme telomerase, which counteracts telomere shortening and thus protects cells.

In the current study, the researchers showed that the mutation in ACD alters the telomere-binding protein TPP1, disrupting the interactions between telomere and telomerase. Without access to telomerase to help maintain telomeres, blood cells lose their structural integrity and die, resulting in bone marrow failure and aplastic anemia.
Nine other genes were previously found to play a role in bone marrow failure disorders. The current study adds ACD to the list, the first time the gene has been shown to have a disease-causing role.
"This improved understanding of the underlying molecular mechanisms may suggest new approaches to treating disorders such as aplastic anemia," said Hakonarson. "For instance, investigators may identify other avenues for recruiting telomerase to telomeres to restore its protective function."

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Adults stop anti-rejection drugs after partial stem-cell transplant reverses sickle cell disease

NIH trial success suggests a new treatment option for older, sicker patients

Half of patients in a trial have safely stopped immunosuppressant medication following a modified blood stem-cell transplant for severe sickle cell disease, according to a study in the July 1 issue of the Journal of the American Medical Association. The trial was conducted at the National Institutes of Health’s Clinical Center in Bethesda, Maryland, by researchers from NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Heart, Lung, and Blood Institute.
The transplant done in the study reversed sickle cell disease in nearly all the patients. Despite having both donor stem-cells and their own cells in their blood, the patients stopped the immunosuppressant medication without experiencing rejection or graft-versus-host disease, in which donor cells attack the recipient. Both are common, serious side effects of transplants.
"Typically, stem-cell recipients must take immunosuppressants all their lives,” said Matthew Hsieh, M.D., lead author on the paper and staff clinician at NIH. “That the patients who discontinued this medication were able to do so safely points to the stability of the partial transplant regimen.”
In sickle cell disease (SCD) sickle-shaped cells block blood flow. It can cause severe pain, organ damage and stroke. The only cure is a blood stem-cell, or bone marrow, transplant. The partial transplant performed in the study is much less toxic than the standard “full” transplant, which uses high doses of chemotherapy to kill all of the patient’s marrow before replacing it with donor marrow. Several patients in the study had less than half of their marrow replaced.
Immunosuppressant medication reduces immune system strength and can cause serious side effects such as infection and joint swelling. In this study, 15 of 30 adults stopped taking the medication under careful supervision one year after transplant and still had not experienced rejection or graft-versus-host disease at a median follow up of 3.4 years.
“Side effects caused by immunosuppressants can endanger patients already weakened by years of organ damage from sickle cell disease,” said John F. Tisdale, M.D., the paper’s senior author and a senior investigator at NIH. “Not having to permanently rely on this medication, along with use of the relatively less-toxic partial stem-cell transplant, means that even older patients and those with severe sickle cell disease may be able to reverse their condition.”
“One of the most debilitating effects of sickle cell disease is the often relentless pain,” added Dr. Hsieh. “Following the transplant, we saw a significant decrease in hospitalizations and narcotics to control that pain.”
The partial transplant used donor stem-cells from healthy siblings. It effectively reversed SCD in 26 of 30 patients and allowed them to achieve stable mixed donor chimerism, a condition in which a person has two genetically distinct cell types in the blood. The study includes patients from an NIH study reported in 2009, in which partial stem-cell transplants reversed SCD in 9 of 10 people.
In the United States, more than 90,000 people have SCD, a genetic disorder found mainly in people of African ancestry. Worldwide, millions of people have the disease.
“The devastating complications associated with sickle cell disease can deeply affect quality of life, ability to work and long-term well-being,” said NIDDK Director Griffin P. Rodgers, M.D., a co-author on the paper. “This study represents an important advance in our efforts to make a potentially transformative treatment available to a wider range of people, especially those who could not tolerate a standard stem-cell transplant or long-term use of immunosuppressants.”
People with sickle cell disease interested in joining NIH blood stem-cell transplant studies may call 1-800-411-1222 or visit http://www.clinicaltrials.gov for more information.
The Sidney Kimmel Cancer Center at Johns Hopkins Medical Institute provided input into trial design.

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Part of the NIH, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI news releases and other materials are available online at: http://www.nhlbi.nih.gov.
The NIDDK, part of the NIH, conducts and supports basic and clinical research and research training on some of the most common, severe and disabling conditions affecting Americans. The institute's research interests include: diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic and hematologic diseases. For more information, visit http://www.niddk.nih.gov.
The NIH Clinical Center (CC) provided clinical laboratory and transfusion medicine support and care for stem-cell donors and recipients. The CC is the clinical research hospital for the NIH. Through clinical research, physician-investigators translate laboratory discoveries into better treatments, therapies and interventions to improve the nation's health. For more information, visit http://clinicalcenter.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

No More Transfusions,Your Child Can Live Without Beta Thalassemia Major

Following is some interesting information we have came across recently. It's solely your decision whether to get in touch with them or not.

Your child can live without beta thalassemia major with no more transfusions,thanks to Bone Marrow Transplant(BMT),  a 30 years reliable technique applied to more than 3,000 patients worldwide. 89% of low risk children are successfully cured.

Ask the free advice to Dr. Pietro Sodani,our co-founder and scientific coordinator, hematologist, BMT expert and inventor of BMT from haploidentical mother to child with thalassemia using protocol 30,who has done in the last 15 years more than 400 BMT in thalassemia with Prof. Lucarelli,the inventor of BMT from matching sibling and the worldwide authority.
 
With Bone Marrow Transplant (BMT) your child can become beta thalassemia major free (no more transfusions). Each child is different and has his own health conditions.
Dr. Pietro Sodani (co-founder and scientific coordinator. Hematologist, BMT expert and inventor of BMT from haploidentical mother to child with thalassemia using protocol 30,who has done in the last 15 years more than 400 BMT in thalassemia with Prof. Lucarelli,the inventor of BMT from matching sibling and the worldwide authority) gives you via email his free professional advice to tell how your child can have a BMT to be thalassemia free,and what the results might be.

 Go to www.curethalassemia.org  for more details

Q&A with Dr. Ellis Neufeld

We  periodically receives questions from patients on a wide range of topics related to thalassemia and its treatment.  We have shared a few of these questions with Dr. Ellis J. Neufeld, the Chair of CAF’s Medical Advisory Board and Associate Chief, Division of Hematology/Oncology at Boston Children’s Hospital. Dr. Neufeld has kindly answered these questions below.

Dr. Ellis J. Neufeld

1.  What is darker colored urine an indication of in thalassemia patients?
People have been fascinated by urine color for thousands of years.  There’s no single answer to this question, and as for many medical questions, it depends why one is asking. Here are some important things to know.
Generally for persons with thalassemia or without, concentrated urine is darker than diluted urine, and if something is coloring the urine more than normal, this effect will be magnified. Ordinarily the most concentrated urine is first morning void, after not drinking all night.
Many thalassemia patients are used to seeing different color urine from medications like iron chelators.  Deferiprone (Ferriprox) turns the urine orange.  Patients on deferoxamine (Desferal or generic) will have reddish urine when the drug (which is colorless by itself) combines with iron.
Darker yellow to light brown urine in thalassemia is from the bilirubin from broken down red blood cells.  This might be especially pronounced in thalassemia intermedia (non-transfusion-dependent thalassemia) or in transfused patients shortly before a next transfusion is due.
Urine that is truly the color of cola or very dark tea is not normal, and could signal increased breakdown of red blood cells (much more bilirubin than normal). Particularly in the few days after a transfusion, or if a person is feeling more tired than usual, this kind of dark urine should prompt a call to your healthcare provider right away.  A check of the urine and blood tests can be reassuring or point to a problem if one has arisen.
Red urine not related to foods (beets) or deferoxamine or laxatives  (ExLax, phenolphthalein) may reflect either bleeding  or hemolysis (breakdown of blood cells) and should always be investigated.
2.  If we know that orange juice can help in the absorption of iron, should we NOT be taking Exjade with orange juice?
Vitamin C intake and levels in thalassemia should be sufficient, but not excessive.  One glass of OJ a day, or ~100 mg of extra vitamin C a day, is just about right.  It’s fine not to take Exjade with orange juice too, but then there needs to be some other way of assuring vitamin C sufficiency, because chelators work better with adequate vitamin C present.

3.  Drinking tea is supposed to inhibit iron absorption; does that include caffeine-free teas?
Only tea with tannins (the brown bitter stuff in black tea) impairs iron absorption and one has to drink a heck of a lot of tea to have this effect.  Herbal teas, say, may have no tannins. But decaffeinated black tea has a normal amount, only the caffeine is removed.

4.  Have there been any studies that have shown that taking a B-complex vitamin daily can slow the breakdown of red blood cells?
Not to my knowledge.  I have not investigated in detail, but we get B vitamins from our food pretty well.  B vitamins like thiamine and B12 and folate are absolutely required to make blood, but that’s a different story.

5.  Can you address whether Exjade should be split into 2 equal doses taken every 12 hours (rather than one every 24), and how combining it with food can affect its effectiveness?
a. “Should be” is a discussion best had with your hematologist.   Exjade CAN BE split into two doses a day, and they don’t necessarily have to be equal, so that if you use three tablets daily, you might split 2 and 1.  There are several theoretical reasons why splitting twice daily might be advantageous.  First, there is less load of the drug all at once. This helps prevent stomach aches and loose stools in some patients on high doses. Second, although on the average, the drug can last up to around 24 hours in the blood, some patients have shorter drug “half-lives” in the blood, and splitting the dose means coverage through more of the day. Third, in a few published abstracts, and in the experience of many treaters, Exjade may be more effective split twice a day (or it may allow higher doses, which are more effective, if it allows less GI side effects).  So at our center we offer or urge twice a day in case of abdominal symptoms or not good-enough effect at higher dose.  Also, see the answer about combining with food (in part b of this answer). If it doesn’t need to be on an empty stomach, twice a day Exjade is much less of a burden.
b. In a study carried out at many expert centers around the world, sponsored by Novartis (the manufacturer), it was proven that Exjade is at least as effective taken with food as not.  As you know, the drug doesn’t dissolve well in water, that’s why it makes a chalky slurry. It dissolves better in fatty foods, and this may be why this is a good option. So we counsel patients  that they can crush the tablets and mix in most anything (but don’t cook or microwave it), and that’s fine. The DRUG LABEL still says to take on an empty stomach in liquid, but we believe this may be because the drug will soon go off-patent, and Novartis hasn’t gotten around to making this change on the label, perhaps for commercial reasons.

6.  Is clumping of platelets a side effect of thalassemia trait?
No.  Rare people have clumping of platelets that isn’t a disease but a lab artifact called “pseudothrombocytopenia” (pseudo as in not real), and your hematologist can sort that out by counting your platelets in a different anticoagulant (that is, a blue top tube instead of purple top).

7.  Are there tests other than creatinine levels to detect kidney damage early?
Yes. This is an important point.  The Exjade package label has specific information on testing for protein in the urine for example.  Exjade raises most everyone’s creatinine without causing significant kidney damage, and then does cause renal disease in a small subset of that group, not related to the creatinine alone.

8.  Is blood warming beneficial to decrease antibody reactions and/or antibody buildup?
In patients with temperature-specific antibodies to red cells, definitely.  In patients without such antibodies, no.  Your center’s blood bank would know this for you. There is no call for general blood warming for example.

Go Get ‘Em, Tiger! One Patient’s Approach to Thalassemia

Marsha DeSalvatore understands the saying about making lemonade when life hands you lemons; this talented and vivacious woman has learned to use the fact that she has thalassemia as a way to express herself through comedy and improvisation. In doing so, she helps herself and educates others about what it means to daily live with a chronic condition. Marsha recently shared her experiences.

You have been using humor as a way to explore thalassemia. Can you talk a little about what you have done, how it helps, etc.?
Marsha: Ever since I was a child, I was aware of how laughing made me feel while I was going through unpleasant situations at the hospital. I have been blessed with a very funny father who is always telling stories, doing impressions and being entertaining. When he came to the hospital to visit me, he would try to make me laugh and that’s when I realized that in those moments I was transported out of what was happening: sad clinic, smells of hospital stuff, needle in my arm, sounds of the transfusion monitor and blood going through my body. Laughing made me feel good even in this unpleasant situation.

Marsha leading a workshop on improvisation and thalassemia at 2014 Patient-Family Conference

Now I am blessed again to be in Rome and have a doctor who prides himself on being the Italian Patch Adams. He is always teasing the patients, telling jokes and making fun of the nurses which makes the clinic into an almost comedy club. Again those moments are when I am transported to happy place whilst being in a painful place.
While living in Rome, I discovered my actress side. I started taking acting classes which eventually led me to working as a comedian today. In the classes, I had to take improv (improvisation) classes. Improv is a form of acting which allows the person to think on their feet in the moment with no script. The goal (in brief words) is working on being in the moment, letting go of your inhibitions, getting out of a person’s comfort zone and having fun. The exercises range from simple warm up exercise to name games to later on evolving scenes with partners that become 2-3 minute mini-plays. As I started getting into this art form which helps me on stage as a comedian, I began to feel the same thing as I did when I was in the hospital: that I was transporting myself to a happy place in a rather uncomfortable situation and applying some of the improv rules to help with everyday life with a chronic illness.

How would you express your philosophy of dealing with the challenges that thalassemia can present?
Don’t fight it, embrace it and find an outlet that gives you happiness whether it’s through exercise or art.
For sure, you will have days when you need to cry, scream, or be alone, but embrace those moments. This is not something that goes away, so try to find ways to live with it.  Remember you are in charge of your illness; it makes up a small percentage of who you are. Find out what you like and who you are.  Use those tools to have an outlet.
For me, it’s laughing with friends, travelling, taking a walk in nature, doing yoga and acting which helps me feel better.  When I get down with my constant hospital life, I do something for myself.

Do you have any advice that you would pass on to others with thalassemia?
As my wise father has always told me, in his thick Italian accent, “Marrrsshha, you got two ways to deal with this thalassemia: you can be angry and hit your head against the wall, but then it is going to bleed – and you need the blood.  Or you can smile and go get ‘em, Tiger!”
Is there anything else you’d like to say?
I hope to be able to use my comedy and do improv with patients of any illness because the thought of giving them a moment of laughter in a moment of pain makes my life as a comedian so much more gratifying. Better than any audience I could ever have.

Thalassemia Patient Authors “Transfusion: A Patient Survival Guide”

Josephine Bila, an individual with thalassemia, has written a book, “Transfusion: A Patient Survival Guide.” 


Tell us a little about “Transfusion: A Patient Survival Guide.”  What motivated you to write it, what is it about, etc.?
Jo:  I was born with beta thalassemia major, so my life depends on receiving transfusions. I’ve been getting them every few weeks for over 35 years. When I was in my twenties, I used to receive blood in an adult outpatient hematology oncology unit. The floor plan was open, so patients would sit in large reclining chairs that were parallel and facing each other. There was a man with cancer who would sit across from me and stare at me for almost the entire duration of my treatment. I would pretend to sleep, but every now and then I would open my eyes and see him gazing at me. In my ever so slight glances, I noticed how this man expressed an intense displeasure and discomfort with his transfusion treatment. He would groan and moan and hold his arm as stiff as a plank of wood. That’s when I realized that he was looking at me curiously not only because I was young, but also because I had emotionally and physically conquered my fear and discomfort with transfusions. I would laugh with the nurses and feel completely tolerant of my pain. That’s when I began to think about how much coping strategy I had taught myself over my lifetime. It’s when I recognized that the tools and practices I had accumulated over the years could be shared and potentially save people from suffering the way I once did.

What are the “take home messages” that you hope readers will pick up from the book?
The primary message of “Transfusion: A Patient Survival Guide”  is that you have a lot more control over your experience in the hospital than you might think. The book shares personal stories from my life that describe how I managed to transform my negative thought patterns and extremely painful physical experiences (I used to get transfusion reactions) into positive thoughts and virtually pain-free physical outcomes.

What was the process of creating the book like?
The process was pretty strange, to be honest. I wrote the entire book two years ago by waking up at two o’clock in the morning and writing for an hour or so over the course of two months. I had a compulsion to put my thoughts onto paper – as if the words had been formulating since the day I noticed that old man suffering. Everything came together with very little effort on my part. The book’s interior design, however, was much more difficult to create. A good friend of mine laid out each page individually and beautifully, in full color, so I feel like he deserves a lot of the credit too.

Do you see this book as an extension of your advocacy efforts on behalf of the thalassemia community and/or the overall patient community?
Yes. I absolutely know for a fact that this book will help any patient or parent of a patient, simply because we need to know how people like ourselves cope and achieve peace in life. I didn’t know any thalassemia patients as I was growing up. Now I go to a hospital where I’m one of many, so I feel so at ease knowing that I’m not alone in my experiences. I want other people to feel this sense of peace. I want parents to know how to console their child when he or she is in need of transfusions. Most of all, I want any person who reads the book to come away feeling stronger, more powerful, and much happier.

What else would you like to share about the book?
You can only buy the book on Amazon (at the moment): amzn.to/1mm2sJW .
I also created a guided meditation to accompany the book, which can be acquired on this page: transfusionsurvivalguide.com.

Is there anything else you’d like to share or to say to those with thalassemia?
Yes, I would love to say that living with thalassemia is not easy. I wasn’t always a beacon of light for people. I spent most of my life angry, sad, and ashamed of having a blood disorder. Then I realized that I was the one designing my life. I decided early on that I could either choose to live a life of misery or I could choose to live a life of happiness. I took the high road. We all have this choice and sometimes it takes an enormous amount of inner strength to push through our own negative momentum, but I know it’s possible. I’m living proof of this fact. I’d love to see you try one small step towards happiness each day. We are so much stronger than we sometimes allow ourselves to be in all areas of life. Let’s show the world what we’re made of!