Age alone no longer should be considered a defining factor when determining whether an older patient with blood cancer is a candidate for stem cell
transplantation. That's the conclusion of the first study summarizing
long-term outcomes from a series of prospective clinical trials of
patients age 60 and over who were treated with the mini-transplant, a
"kinder, gentler" form of allogeneic (donor cell) stem cell
transplantation developed at Fred Hutchinson Cancer Research Center. The
findings are published Nov. 2 in JAMA, The Journal of the American
Medical Association.
"Age is no longer a barrier to allogeneic transplant," said Mohamed
Sorror, M.D., M.Sc., an assistant member of the Hutchinson Center's
Clinical Research Division and corresponding author of the paper.
Sorror and colleagues found that the five-year rates of overall and
disease-progression-free survival among mini-transplant patients were 35
percent and 32 percent, respectively. Patients in three age groups 60
to 64, 65 to 69 and 70 to 75 had comparable survival rates, which
suggested that age played a limited role in how patients tolerate the
mini-transplant. Increased medical problems unrelated to cancer
(comorbidities) and a higher degree of cancer aggressiveness were the
two factors that affected survival among those older patients. For
example, patients who had less-aggressive cancer and fewer comorbidities
had a five-year survival rate of 69 percent, while patients with more
aggressive cancer and a significant number of comorbidities had a
survival rate of 23 percent, regardless of age.
Although a long-term survival rate of one-third of patients may seem
low, these patients all would have died of their diseases within a
matter of months without a transplant. "The majority of patients were
referred for a transplant after they had exhausted all forms of
conventional therapy," said Sorror, who works in the research group led
by Rainer Storb, M.D., who developed the mini-transplant.
"While there is much room for improvement, particularly with regard to
relapse, these results are encouraging given the poor outcomes with
non-transplantation treatments, especially for patients with high-risk
AML (acute myeloid leukemia), fludarabine-refractory CLL (chronic lymphocytic leukemia) or progressive lymphoma," the authors wrote.
The mini-transplant, known in medical circles as nonmyeloablative
transplantation, was developed by researchers at the Hutchinson Center
for older and medically sicker patients who otherwise could not tolerate
the standard, more-toxic, high-dose regimens used to prepare patients
for transplantation.
11/4/11
10/19/11
Scientists correct sickle cell disease in mice
U.S. scientists have found a way to
get mice with a form of sickle cell disease to make normal red blood
cells, offering a potential new way to treat the blood disorder in
people, they reported on Thursday.
Adults with sickle cell disease make mutant, sickle-shaped forms of hemoglobin, the protein in red blood cells that is vital for carrying oxygen to the body's tissues.
These deformed cells block small blood vessels, causing pain, strokes, organ dysfunction and premature death.
But this problem occurs only after birth.
During development, a fetus uses one gene to make a fetal form of hemoglobin, but switches to another after birth, and problems with this adult gene are what lead to sickle cell disease.
A team led by Dr. Stuart Orkin of Harvard Medical School, Children's Hospital and the Howard Hughes Medical Institute in Boston, earlier had discovered that a protein called BCL11A is responsible for making the switch from fetal hemoglobin to adult hemoglobin.
In the latest study, published in the journal Science, the team looked to see what would happen if they blocked production of the BCL11A protein in mice with sickle cell disease.
They found that when the protein was disabled, the mice switched back to producing fetal hemoglobin. And mice that once exhibited symptoms of sickle cell disease improved.
"This discovery provides an important new target for future therapies in people with sickle cell disease," Dr. Susan Shurin, acting director of the NIH's National Heart, Lung, and Blood Institute, which co-funded the study, said in a statement.
"More work is needed before it will be possible to test such therapies in people, but this study demonstrates that the approach works in principle."
Sickle cell disease affects 100,000 Americans and 3 million to 5 million people globally. It is most prevalent in people of African, Hispanic, Mediterranean and Middle Eastern descent.
There is no widely available cure. Bone marrow transplants work for some patients, but the treatment is risky and only available to patients with relatives who can donate compatible and healthy bone marrow to them.
Adults with sickle cell disease make mutant, sickle-shaped forms of hemoglobin, the protein in red blood cells that is vital for carrying oxygen to the body's tissues.
These deformed cells block small blood vessels, causing pain, strokes, organ dysfunction and premature death.
But this problem occurs only after birth.
During development, a fetus uses one gene to make a fetal form of hemoglobin, but switches to another after birth, and problems with this adult gene are what lead to sickle cell disease.
A team led by Dr. Stuart Orkin of Harvard Medical School, Children's Hospital and the Howard Hughes Medical Institute in Boston, earlier had discovered that a protein called BCL11A is responsible for making the switch from fetal hemoglobin to adult hemoglobin.
In the latest study, published in the journal Science, the team looked to see what would happen if they blocked production of the BCL11A protein in mice with sickle cell disease.
They found that when the protein was disabled, the mice switched back to producing fetal hemoglobin. And mice that once exhibited symptoms of sickle cell disease improved.
"This discovery provides an important new target for future therapies in people with sickle cell disease," Dr. Susan Shurin, acting director of the NIH's National Heart, Lung, and Blood Institute, which co-funded the study, said in a statement.
"More work is needed before it will be possible to test such therapies in people, but this study demonstrates that the approach works in principle."
Sickle cell disease affects 100,000 Americans and 3 million to 5 million people globally. It is most prevalent in people of African, Hispanic, Mediterranean and Middle Eastern descent.
There is no widely available cure. Bone marrow transplants work for some patients, but the treatment is risky and only available to patients with relatives who can donate compatible and healthy bone marrow to them.
10/17/11
FDA Approves New Treatment Option for Patients with Thalassemia
Gina Cioffi
Cooley's Anemia Foundation
For many years, the only FDA-approved chelator was Desferal, which must be administered by pumping the drug into the body for 8-12 hours, 5-7 nights per week. In 2005, the FDA approved Exjade, a chelator that is administered orally.
“The major cause of death in our patient population is iron-related heart failure,” says Viola. “And with a very significant percentage of our population unable to use either Desferal or Exjade, there is a vital need for another option; that option is Ferriprox.”
Cooley's Anemia Foundation
The Cooley's Anemia Foundation Applauds FDA Approval of Ferriprox, Iron Chelator for People with Thalassemia. The Foundation Believes a Wider "Menu" of Treatment Options is Crucial for Each Individual Patient to Receive Optimal Treatment
New York, NY (PRWEB) October 14, 2011
The Cooley’s Anemia Foundation (CAF), the only national non-profit
dedicated solely to fighting the genetic blood disorder thalassemia,
applauds a Food and Drug Administration (FDA) decision today to approve
the new drug application for the oral chelator, Ferriprox. This action
follows a 10-2 vote on September 14, 2011 by the Oncology Drugs Advisory Committee to recommend the approval of this drug.
New York, NY (PRWEB) October 14, 2011
“As the premier voice of the
thalassemia community in the United States, we are thrilled that our
patients will have the benefit of this drug which has proven beneficial
to patients throughout the world,” says CAF National President Anthony J. Viola. “The FDA clearly responded to the overwhelming need for this drug in our patient population
and has provided those patients needing daily drug therapy to remove
iron, an option that has improved cardiac health and prolonged life in
thousands of patents over the past decade.”
Ferriprox is an iron chelator,
which is a drug that is used to help rid the body of excess iron, a
serious and often fatal complication in thalassemia. Because
individuals with the severe form of thalassemia are born with a life
threatening anemia, they require lifelong blood transfusions as often as
every two weeks. These transfusions overload the body with iron; if it
is not removed, it settles in the organs, causing heart and liver
failure, as well as numerous other complications.
For many years, the only FDA-approved chelator was Desferal, which must be administered by pumping the drug into the body for 8-12 hours, 5-7 nights per week. In 2005, the FDA approved Exjade, a chelator that is administered orally.
Ferriprox is also an oral chelator.
In addition to being easier to administer than Desferal, Studies
published in Europe demonstrate that use of Ferriprox has been shown to
protect the heart from iron accumulation, a crucial concern for
individuals with thalassemia.
“The major cause of death in our patient population is iron-related heart failure,” says Viola. “And with a very significant percentage of our population unable to use either Desferal or Exjade, there is a vital need for another option; that option is Ferriprox.”
“We have seen too many patients die
too young,” Viola concludes. “Our patients’ lives depend upon having
more treatment options available to them. The FDA addressed the unmet
medical needs of these desperately ill patients and provided approval
for a drug that will help them. Their decision has the opportunity to
extend our patient’s lives and significantly improve their quality of
life.”
Founded in 1954, the Cooley’s Anemia Foundation (http://www.cooleysanemia.org;
(212-279-8090) is the only national non-profit organization dedicated
solely to thalassemia. The Foundation’s mission is advancing the
treatment and cure for this fatal blood disease, enhancing the quality
of life of patients and educating the medical profession, trait carriers
and the public about Cooley's anemia/thalassemia major.
10/14/11
Thalassemia in Pregnancy - Organ Functions
Cardiac function and transfusion requirements
During pregnancy, the fluid component of the blood normally increases. This can increase the degree of anemia, which leads to the need for more frequent blood transfusions. Increased anemia can also result in the heart having to work harder to get adequate oxygen to all of the body's tissues. Increased blood volume can also put stress on the heart. In thalassemia, the heart may already be under stress from the damaging effects of iron overload. Therefore, it is important to have cardiac function checked prior to and throughout pregnancy. Regular attend-ance at scheduled transfusion appointments is also critical in order to reduce anemia and lessen the work that the heart must do.
Liver function
A liver biopsy may be indicated prior to pregnancy to assess the degree of iron overload. This information may be helpful in deciding whether or not to discontinue iron chelation. A liver biopsy can also help determine if there has been damage from iron deposition or previous hepatitis infection. Blood tests throughout pregnancy can also assess liver function.
Endocrine function
Individuals with thalassemia have an increased chance of developing insulin-dependent diabetes as a result of iron overload. The stress of pregnancy can worsen this condition, which can be detrimental to the health of the mother and developing baby. It is important to stabilize diabetes prior to becoming pregnant and to maintain adequate treatment throughout pregnancy. Thyroid function can also be impaired due to iron overload in the woman with thalassemia.
Splenic function
The spleen removes abnormal red blood cells from the circulation and performs important immune functions. Individuals who have thalassemia have unusually large numbers of abnormal red blood cells. The spleen becomes very active in removing these cells. This activity can enlarge the spleen making it more effective at removing even larger numbers or cells, causing a hemolytic anemia. During pregnancy, there is a greater need for hemoglobin both for normal growth and development of the fetus and due to the fact that the blood volume of the mother will increase dramatically. During this time, transfusion requirements in the pregnant woman is increased, particularly during the last trimester of pregnancy. If transfusion in adequate, the bone marrow will be suppressed and the work of the spleen can be decreased. Occasionally, this will lead to some decrease in spleen size and activity.
During pregnancy, the fluid component of the blood normally increases. This can increase the degree of anemia, which leads to the need for more frequent blood transfusions. Increased anemia can also result in the heart having to work harder to get adequate oxygen to all of the body's tissues. Increased blood volume can also put stress on the heart. In thalassemia, the heart may already be under stress from the damaging effects of iron overload. Therefore, it is important to have cardiac function checked prior to and throughout pregnancy. Regular attend-ance at scheduled transfusion appointments is also critical in order to reduce anemia and lessen the work that the heart must do.
Liver function
A liver biopsy may be indicated prior to pregnancy to assess the degree of iron overload. This information may be helpful in deciding whether or not to discontinue iron chelation. A liver biopsy can also help determine if there has been damage from iron deposition or previous hepatitis infection. Blood tests throughout pregnancy can also assess liver function.
Endocrine function
Individuals with thalassemia have an increased chance of developing insulin-dependent diabetes as a result of iron overload. The stress of pregnancy can worsen this condition, which can be detrimental to the health of the mother and developing baby. It is important to stabilize diabetes prior to becoming pregnant and to maintain adequate treatment throughout pregnancy. Thyroid function can also be impaired due to iron overload in the woman with thalassemia.
Splenic function
The spleen removes abnormal red blood cells from the circulation and performs important immune functions. Individuals who have thalassemia have unusually large numbers of abnormal red blood cells. The spleen becomes very active in removing these cells. This activity can enlarge the spleen making it more effective at removing even larger numbers or cells, causing a hemolytic anemia. During pregnancy, there is a greater need for hemoglobin both for normal growth and development of the fetus and due to the fact that the blood volume of the mother will increase dramatically. During this time, transfusion requirements in the pregnant woman is increased, particularly during the last trimester of pregnancy. If transfusion in adequate, the bone marrow will be suppressed and the work of the spleen can be decreased. Occasionally, this will lead to some decrease in spleen size and activity.
10/13/11
Anemia in Postmenopausal Women Linked With Poor Nutrition
Emma Hitt, PhD
Anemia is linked to poor nutrition in postmenopausal women, according to a recent observational study of the Women's Health Initiative (WHI).
Cynthia A. Thomson, PhD, RD, with the University of Arizona, in Tucson, and colleagues reported their findings in the April issue of the Journal of the American Dietetic Association.
According to the researchers, nutritional anemia includes those types associated with prolonged inadequate intake of folate, vitamin B12, iron, protein, and vitamin C.
Dr. Thomson and colleagues hypothesized that a greater number of dietary inadequacies of these nutrients would be associated with a greater risk for incident and persistent anemia.
To evaluate their hypothesis, the researchers used data from the WHI observational cohort study (WHI-OS), which contained a longitudinal sample of postmenopausal women. A total of 93,676 postmenopausal women between the ages of 50 and 79 years were recruited at 40 clinical sites across the United States. Women were enrolled from 1993 until 1998, and data collection was completed in 2000.
Diet was assessed by a food frequency questionnaire for iron, vitamin B12, folate, red meat, and cold breakfast cereal. Dietary intake for women older than 50 years was used as a reference to measure inadequacies. Anemia was defined as a blood hemoglobin concentration of less than 120 g/L in women. Persistent anemia was defined as anemia present at each measurement.
Anemia was identified in 3979 (5.5%) of the participants. Inadequate intake of anemia-associated nutrients was less frequent in non-Hispanic whites (7.4%) vs other racial or ethnic groups (14.6% - 16.3%).
Smoking, age, and body mass index were associated with anemia. Women with anemia reported a lower dietary intake of red meat, folate, vitamin B12, vitamin C, and iron. In addition, deficiencies in dietary intake of 1 nutrient were associated with a 21% greater risk for persistent anemia (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.05 - 1.41), whereas 3 deficiencies in dietary intake resulted in a 44% increase in the risk for persistent anemia (OR, 1.44; 95% CI, 1.20 - 1.73).
Deficiencies in total intake of 1 nutrient were associated with a 34% increased risk for persistent anemia (OR, 1.34; 95% CI, 1.14 - 1.56). Regarding deficiencies in total intake of 3 nutrients, the risk increased to 56% (OR, 1.56; 95% CI, 1.25 - 1.95).
Editorial: Nutrient Measurements Costly
According to editorialists Lisa Tussing-Humphreys, PhD, RD, with the US Department of Agriculture–Agriculture Research Service, in Los Angeles, California, and Carol Braunschweig, PhD, RD, with the University of Illinois, in Chicago, this study provides "one of the largest prospective assessments of diet and anemia in US postmenopausal women."
They add that the findings "lend credibility to the use of an FFQ [food frequency questionnaire] for large epidemiological studies investigating the relationship between diet and anemia risk."
However, according to the editorialists, the mean nutrient intakes reported indicate that "a portion of the anemia observed in the WHI-OS cohort was not diet-related," they write. "For example, it is well known that decreases in hemoglobin occur from nutrient deficiencies only when stores are nearly exhausted."
In addition, although the accurate assessment of anemia allows clinicians to classify the type of anemia and recommend suitable treatment options, inclusion of these measurements in large epidemiologic studies is "cost-prohibitive and unlikely."
Anemia is linked to poor nutrition in postmenopausal women, according to a recent observational study of the Women's Health Initiative (WHI).
Cynthia A. Thomson, PhD, RD, with the University of Arizona, in Tucson, and colleagues reported their findings in the April issue of the Journal of the American Dietetic Association.
According to the researchers, nutritional anemia includes those types associated with prolonged inadequate intake of folate, vitamin B12, iron, protein, and vitamin C.
Dr. Thomson and colleagues hypothesized that a greater number of dietary inadequacies of these nutrients would be associated with a greater risk for incident and persistent anemia.
To evaluate their hypothesis, the researchers used data from the WHI observational cohort study (WHI-OS), which contained a longitudinal sample of postmenopausal women. A total of 93,676 postmenopausal women between the ages of 50 and 79 years were recruited at 40 clinical sites across the United States. Women were enrolled from 1993 until 1998, and data collection was completed in 2000.
Diet was assessed by a food frequency questionnaire for iron, vitamin B12, folate, red meat, and cold breakfast cereal. Dietary intake for women older than 50 years was used as a reference to measure inadequacies. Anemia was defined as a blood hemoglobin concentration of less than 120 g/L in women. Persistent anemia was defined as anemia present at each measurement.
Anemia was identified in 3979 (5.5%) of the participants. Inadequate intake of anemia-associated nutrients was less frequent in non-Hispanic whites (7.4%) vs other racial or ethnic groups (14.6% - 16.3%).
Smoking, age, and body mass index were associated with anemia. Women with anemia reported a lower dietary intake of red meat, folate, vitamin B12, vitamin C, and iron. In addition, deficiencies in dietary intake of 1 nutrient were associated with a 21% greater risk for persistent anemia (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.05 - 1.41), whereas 3 deficiencies in dietary intake resulted in a 44% increase in the risk for persistent anemia (OR, 1.44; 95% CI, 1.20 - 1.73).
Deficiencies in total intake of 1 nutrient were associated with a 34% increased risk for persistent anemia (OR, 1.34; 95% CI, 1.14 - 1.56). Regarding deficiencies in total intake of 3 nutrients, the risk increased to 56% (OR, 1.56; 95% CI, 1.25 - 1.95).
Editorial: Nutrient Measurements Costly
According to editorialists Lisa Tussing-Humphreys, PhD, RD, with the US Department of Agriculture–Agriculture Research Service, in Los Angeles, California, and Carol Braunschweig, PhD, RD, with the University of Illinois, in Chicago, this study provides "one of the largest prospective assessments of diet and anemia in US postmenopausal women."
They add that the findings "lend credibility to the use of an FFQ [food frequency questionnaire] for large epidemiological studies investigating the relationship between diet and anemia risk."
However, according to the editorialists, the mean nutrient intakes reported indicate that "a portion of the anemia observed in the WHI-OS cohort was not diet-related," they write. "For example, it is well known that decreases in hemoglobin occur from nutrient deficiencies only when stores are nearly exhausted."
In addition, although the accurate assessment of anemia allows clinicians to classify the type of anemia and recommend suitable treatment options, inclusion of these measurements in large epidemiologic studies is "cost-prohibitive and unlikely."
10/6/11
Hemoglobinopathy and thalassemia detection
Traditional methods and a novel method — capillary electrophoresis technology
By Aigars Brants, PhD
In humans, two pairs of unlike globin chains combine with four heme groups to form hemoglobin (Hb), a protein that is carried by red cells and picks up oxygen in the lungs and delivers it to the peripheral tissues. One of the globin chain pairs in hemoglobin is always alpha (with the exception of the very first weeks of embryogenesis), while the second pair is “non-alpha.” That is, it can be made of beta- (ß), delta- (d), or gamma (g) chains.
In the healthy newborn, Hb F (a2g2) is the major hemoglobin (~75%). Fetal hemoglobin (Hb F) is replaced by Hb A (a2ß2) and Hb A2 (a2d2) during the first six to 12 months of life. In healthy adults, hemoglobin is comprised of Hb A (~97%) and Hb A2 (~2.7%), with only trace amounts of Hb F, if any.
Two types of disorders may affect globin chains—qualitative and quantitative. Qualitative disorders, i.e., hemoglobinopathies, result from any of the following: i) substitution of one amino acid for another (as in Hb S and Hb C); ii) deletion of a portion of the amino acid sequence (as in Hb Gun Hill); iii) abnormal hybridization between two chains during meiosis (as in Hb Lepore); and iv) abnormal elongation of the globin chain (as in Hb Constant Spring). Obviously, any alterations listed above lead to changes in molecule structure or charge and they can be detected with the appropriate methodology.
Currently, over 1,400 Hb variants are listed in the globin chain database, with the majority of them being beta chain variants.
Thalassemias are quantitative disorders affecting the rate of otherwise normal hemoglobin synthesis. The ß-thalassemia carrier state is a benign condition with mild anemia, red blood cell hypochromia and microcytosis, and an elevated Hb A2 level. In comparison, severe disease (ß-thalassemia major) requires lifelong blood transfusions and chelation therapy.
Since increase in Hb A2 concentration is indicative of beta-thalassemia, it is useful to obtain an accurate relative Hb A2 value. With many testing methods, common Hb variants can interfere with an accurate Hb A2 quantitation. It is also important to account for delta chain Hb variants in the sample; if any are present, the delta chain variant concentration (percentage) must be added to the Hb A2 value to obtain an accurate total Hb A2 concentration.
Alpha-thalassemia affects the synthesis of alpha globin chains, and the severity of disease is dependent on the extent of gene deletion. Loss of two out of four alpha-chains encoding genes results in an a-thalassemia trait, characterized by microcytosis with little or no anemia. Loss of three genes results in Hb H (4ß chains) disease, a moderate hemolytic anemia, while loss of all four genes is incompatible with independent life.
Electrophoretic hemoglobin separation methods
Electrophoresis has long been the method of choice in hematological laboratories for qualitative and quantitative hemoglobin analyses. Currently, four different techniques are routinely used in the lab setting: 1) alkaline and acid gel electrophoresis; 2) isoelectric focusing (IEF); 3) high-pressure liquid chromatography (HPLC); and 4) capillary electrophoresis (CE).
Sebia Electrophoresis provides multiple platforms for the detection of hemoglobinopathies and thalassemias—fully automated capillary electrophoresis systems and a semi-automated agarose gel system to accommodate both alkaline and acid agarose gel electrophoresis.
Alkaline and acid agarose electrophoresis
Because of its simplicity, alkaline gel electrophoresis is one of the most popular methods for Hb screening. Semi-automated agarose gel electrophoresis is also cost-effective for low- to medium-volume laboratories. However, the technique is relatively laborious, requiring manual sample preparation. Red blood cells must be washed in saline to remove plasma proteins and to eliminate non-hemoglobin bands on the gel. Electrophoresis at alkaline pH (8.5) allows for the separation of the major hemoglobins and a number of less common Hb variants. Visualization of the Hb bands is done by automated staining of the gel with amido black. The clear background of the gels enables measuring the concentration of individual fractions by densitometric scanning. However, due to the precision and accuracy of Hb in low concentrations (Hb A2 for example), the College of American Pathologists (CAP) no longer recommends the use of densitometric scanning for quantification of Hb A2. With alkaline agarose gel testing, some common Hb variants comigrate, such as Hb C, Hb E, Hb A2 & Hb O-Arab and Hb S, Hb D and Hb G.
In order to separate some Hb variants that commonly comigrate at alkaline conditions, the sample may also be analyzed on gel at an acidic pH (6.0). In these conditions, molecular charge will differ and migration patterns will change. As a result, Hb S can be differentiated from Hb D, and Hb C can be differentiated from Hb E.
Isoelectric focusing
IEF provides excellent separation of many hemoglobin variants and detects fast-migrating or low concentration hemoglobin variants such as Hb H, Hb Bart’s, and delta chain variants.
IEF gels contain special molecules—ampholytes—that create a pH gradient in an electrical field. When a pH gradient is present, hemoglobin molecules migrate to a position on the gel where the net charge equals zero (0), resulting in very narrow and focalized bands. On IEF gels, Hb C separates from Hb E and Hb O-Arab, and Hb S from Hb D and Hb G. IEF gels, however, are processed manually and require a significant amount of technical time. Additionally, IEF results are qualitative, and interpreting results requires significant experience.
High pressure liquid chromotagraphy
HPLC is a pressure-driven technique. Hemoglobin samples are injected into a resin column and retained based on the charge. The eluting solution that competes for the negatively charged resin is added in increasing concentration. Hemoglobin variants elute from the column and are detected at 415 nm, then at 690 nm to correct the baseline of the result. The hemoglobin retention time (from injection until the maximum point of each peak) is calculated and plotted on a chromatogram.
HPLC instruments are primarily indicated for the measurement of Hb A2 and F, but also provide data (retention times) on many Hb variants. However, HPLC should not be used as the sole method for identification of hemoglobin variants.1 HPLC is very complementary to CE technology; together these two automated methodologies provide valuable data for result interpretation.2,3 HPLC techniques result in patterns that are relatively complex and require training and experience for interpretation of results.4
Capillary electrophoresis
CE technology utilizes liquid flow electrophoresis—buffer replaces agarose gel as the medium. Hemoglobin variants are separated by electroosmotic flow at an alkaline pH (9.4) using negatively charged silica capillaries and high voltage. Multiple samples undergo an eight-minute high-resolution separation, concurrently. A high-resolution hemoglobin separation is obtained, similar to IEF separation. The ideal wavelength of 415 nm is utilized for hemoglobin detection with CE. The result, or electropherogram, is made up of 300 consecutive readings (dots) and is divided into 15 zones. To facilitate interpretation, results are automatically positioned with regard to the Hb A and Hb A2 fraction in the sample. Hemoglobins (normal and variant) are displayed as peaks, and the zone to which a variant belongs is identified automatically by the system. An on-board hemoglobin library is present in the form of a drop-down list and lists all of the normal and variant hemoglobins that may be present within a particular zone.
With Sebia’s CE systems, packed red blood cell samples are utilized for analysis. Plasma is removed from samples, and the bar-coded primary sample tube is loaded onto the instrument; all other steps in sample processing and separation are performed automatically by the system.
More features of CE technology
- In one analysis, separation of Hb S from Hb D, and Hb C from Hb E (and from Hb A2).
- Precise, quick quantification of Hb F and Hb A2, even in the presence of Hb S.5
- Posttranslational Hb variants (such as glycated HbS1c) do not separate from the main fractions.6
- Delta chain variants, alpha chain variants, and other minor Hb fractions are readily visualized.8
- Hb H and Hb Bart’s are more readily detected and measured by CE than by the HPLC method .4
Multiuse instrument
Sebia systems may be used for other types of analysis, including serum/urine protein electrophoresis, immunotyping (automated immunofixation alternative), and CDT (a marker for chronic alcohol abuse)8
CAP requires the use of a second, complementary technique for abnormal hemoglobin results. CE is most complementary with acid gel electrophoresis and HPLC. By combining CE and HPLC methodologies, one can significantly reduce the number of unusual hemoglobin variants that can be confused with normal hemoglobins or common Hb variants (2).
Newborn screening with dried blood spot samples
Sebia’s newest FDA-cleared CE assay for hemoglobinopathy testing is Capillarys Neonat Hb Fast. It is used for the screening of newborn blood samples collected on Guthrie Cards. Newborn dried blood spot samples are screened for the presence of normal hemoglobins (F and A) and common hemoglobin variants to include S, C, D, E, and Bart’s. The system is fully automated and fast, with an instrument throughput of 96 results in two hours. The fast throughput is accomplished due to eight simultaneous analyses taking place; a high-resolution seven-minute migration occurs for each newborn sample with results similar to IEF separation. Result interpretation is aided by automatically color-coded curves (normal or abnormal results) and on-board hemoglobin library by zone. All normal hemoglobins and common variants migrate in different zones—Bart’s, A, F, D, S, E, A2, and C.
The following table lists HPLC migration characteristics in the presence of common variants.
Hb present | Hb A2 result | Hb F result | Comments |
S | falsely elevated | coelution of Hb S1c fraction with A2 (4) | |
E | falsely elevated | coelution of Hb E with A2 (4) | |
D | underestimated | (3) | |
G-Philadelphia | falsely elevated | coelution of G-Philadelphia with A2 | |
Lepore | falsely elevated | coelution of Lepore with A2 (3) | |
A1c (elevated) | falsely elevated | (3) |
5/25/11
Poor Eating Habits May Lead to Anemia in Older Women
Study finds that as nutrient intake declines, risk rises
FRIDAY, March 25 (HealthDay News) -- A poor diet is associated with a greater risk of developing anemia among postmenopausal women, a new study has found.
Researchers analyzed data from 72,833 older women in the United States and found that deficiencies in more than a single nutrient were associated with a 21 percent increased risk of persistent anemia. Risk increased 44 percent with deficiencies in three nutrients.
Women with anemia consumed less protein, folate, vitamin B12, iron, vitamin C and red meat than did others, the study found. The results are published in the April issue of the Journal of the American Dietetic Association.
Inadequate nutrient intake was less frequent among whites than in other racial or ethnic groups: 7.4 percent, compared with 14.6 percent of Asian/Pacific Islanders, 15.2 percent of Native Americans/Alaskans, 15.3 percent of blacks and 16.3 percent of Hispanics.
The researchers also found that the use of multivitamin and mineral supplements was not associated with lower rates of anemia. Age, body mass index and smoking were associated with anemia.
Anemia has been linked to an increased risk of death and, "anemia, particularly iron deficiency, has been associated with reduced capacity for physical work and physical inactivity, injury related to falls and hospitalizations, making this an important health-care concern in the aging," lead investigator Cynthia A. Thomson, associate professor of nutritional sciences at the University of Arizona in Tucson, said in a journal news release.
"Efforts to identify anemia that may be responsive to modifiable factors, such as diet to improve health outcomes, are needed," the researchers concluded. "Additional efforts to regularly evaluate postmenopausal women for anemia should be considered and should be accompanied by an assessment of dietary intake to determine adequacy of intake of anemia-associated nutrients, including iron, vitamin B12 and folate," they wrote.
"While the type of anemia is often designated by a more comprehensive biochemical assessment than hemoglobin alone, nutritional therapy to improve overall nutrient-density and quality of the diet should also be a clinical focus," Thomson and colleagues said.
Researchers analyzed data from 72,833 older women in the United States and found that deficiencies in more than a single nutrient were associated with a 21 percent increased risk of persistent anemia. Risk increased 44 percent with deficiencies in three nutrients.
Women with anemia consumed less protein, folate, vitamin B12, iron, vitamin C and red meat than did others, the study found. The results are published in the April issue of the Journal of the American Dietetic Association.
Inadequate nutrient intake was less frequent among whites than in other racial or ethnic groups: 7.4 percent, compared with 14.6 percent of Asian/Pacific Islanders, 15.2 percent of Native Americans/Alaskans, 15.3 percent of blacks and 16.3 percent of Hispanics.
The researchers also found that the use of multivitamin and mineral supplements was not associated with lower rates of anemia. Age, body mass index and smoking were associated with anemia.
Anemia has been linked to an increased risk of death and, "anemia, particularly iron deficiency, has been associated with reduced capacity for physical work and physical inactivity, injury related to falls and hospitalizations, making this an important health-care concern in the aging," lead investigator Cynthia A. Thomson, associate professor of nutritional sciences at the University of Arizona in Tucson, said in a journal news release.
"Efforts to identify anemia that may be responsive to modifiable factors, such as diet to improve health outcomes, are needed," the researchers concluded. "Additional efforts to regularly evaluate postmenopausal women for anemia should be considered and should be accompanied by an assessment of dietary intake to determine adequacy of intake of anemia-associated nutrients, including iron, vitamin B12 and folate," they wrote.
"While the type of anemia is often designated by a more comprehensive biochemical assessment than hemoglobin alone, nutritional therapy to improve overall nutrient-density and quality of the diet should also be a clinical focus," Thomson and colleagues said.
5/24/11
4-year-old cured of Thalassemia major with stem cell transplant
Ahmedabad doctorshave carried out a rare successful stem cell transplant on a four-year-old girl suffering from Thalassemia major, relieving her of life-long blood transfusions.
Isha Gohel from Saurastra, who was diagnosed of suffering from advanced stages of Thalassemia, had started receiving blood transfusions at the age of 18 months.
When she was brought to Apollo hospital in Ahmedabad, doctors after investigations found that she was a case of class 3 Thalassemia Major. Since she did not get good quality blood transfusion, her condition was very poor. She had developed marked enlargement of the spleen leading to further poor response to blood transfusions.
Terming Isha's case as challenging, Dr Chirag A Shah, haematologist, Apollo hospital here, said that they followed the style of treatment of Dr G Lucarelli from the Mediterranean Institute of Haematology - an international centre for transplantation in thalassemia and Sickle Cell Anaemia - in Italy who has successfully treated advanced cases of thalassemia.
Her spleen was removed and stems cells from Isha's two-year-old brother were transplanted. "We followed his (Lucarelli's) formulae for treatment of Isha and we were successful," he said.
"Stemcell transplant in advanced cases of thalassemia results in poor outcome. Such patients are not advised a transplant as they frequently have poor results and have high risk of complications," Shah said.
He said that Isha's case was difficult for them as her spleen had blown out of proportion and her liver too was damaged due to iron deposits.
Giving details of her treatment, he said, "We first surgically removed her spleen in January and the following month we started on a special protocol of medicines to reduce her risk of being Class 3. This continued for over one month until finally she underwent stem cell transplant procedure in April. The stem cells were from her younger brother."
Isha is now on the road to recovery and and will be transfusion free forever as her underlying Thalassemia major is now cured after stem cell transplant.
Isha Gohel from Saurastra, who was diagnosed of suffering from advanced stages of Thalassemia, had started receiving blood transfusions at the age of 18 months.
When she was brought to Apollo hospital in Ahmedabad, doctors after investigations found that she was a case of class 3 Thalassemia Major. Since she did not get good quality blood transfusion, her condition was very poor. She had developed marked enlargement of the spleen leading to further poor response to blood transfusions.
Terming Isha's case as challenging, Dr Chirag A Shah, haematologist, Apollo hospital here, said that they followed the style of treatment of Dr G Lucarelli from the Mediterranean Institute of Haematology - an international centre for transplantation in thalassemia and Sickle Cell Anaemia - in Italy who has successfully treated advanced cases of thalassemia.
Her spleen was removed and stems cells from Isha's two-year-old brother were transplanted. "We followed his (Lucarelli's) formulae for treatment of Isha and we were successful," he said.
"Stemcell transplant in advanced cases of thalassemia results in poor outcome. Such patients are not advised a transplant as they frequently have poor results and have high risk of complications," Shah said.
He said that Isha's case was difficult for them as her spleen had blown out of proportion and her liver too was damaged due to iron deposits.
Giving details of her treatment, he said, "We first surgically removed her spleen in January and the following month we started on a special protocol of medicines to reduce her risk of being Class 3. This continued for over one month until finally she underwent stem cell transplant procedure in April. The stem cells were from her younger brother."
Isha is now on the road to recovery and and will be transfusion free forever as her underlying Thalassemia major is now cured after stem cell transplant.
5/14/11
"Behavioral Strategies for Parents" Webinar Available Online
Dr. Lauren Mednick's presentation on "Behavioral Strategies for Parents of Children with Thalassemia," CAF's March 2 webinar, is now available for watching.
Lauren Mednick, PhD, is an assistant in Psychology at Children’s Hospital Boston and is on the faculty at Harvard Medical School. She received her B.S. in Psychology from the University of Illinois and both her Master of Philosophy and her PhD in Clinical Child Psychology, with an emphasis on behavioral medicine, from The George Washington University. Her subsequent clinical, teaching and research efforts have focused on helping children and families cope with medical stressors. The majority of her time is spent in direct clinical care, conducting outpatient therapy with children and adolescents diagnosed with acute and chronic medical conditions, including thalassemia. Dr. Mednick also has an interest in how a parent is coping impacts a child’s physical and emotional well-being and focuses much of her work on investigating stress and coping in parents of children diagnosed with various medical conditions. CAF is thrilled to be able to offer the experience and knowledge that Dr. Mednick has learned working with families with thalassemia, as well as with other chronic conditions.
Kolkata conducts unique Thalassemia treatment
A Kolkata hospital conducted the first successful mixed stem cell (cord blood and bone marrow) transplant surgery to give new life to a child suffering form the HbE-Beta Thalassemia disease.
Dr. Ashish Mukherjee conducted the surgery on Apr 3 to treat a five year old boy named Moinam at the Netaji Subhash Chandra Bose Cancer research Institute in Kolkata.
For conducting this treatment they took the stem cells from the cord blood of the second child (sister of Moinam) of Ashim Pal and Monisha Pal and then preserved it under specified conditions at CordLife, lrgest network of stem cell bank with full processing.
"When stem cells are needed to treat a life threatening disease, doctors ans can effectively predict transplant success by evaluating two factors-HLA compatibility and stem cell count," Prosanto Chowdhury, Medial Director, Cord Life India, said.
"Transplants like these confirm CordLife's technology and our assurance to parents who bank with us their baby's cord blood. HLA matching was undertaken which provided that the tissues of both the children matched and the treatment could proceed. This is the first case of mixed stem cell transplant in India," he said.
Thalassemia is an inherited blood disorder in which the body produces an abnormal form of haemoglobin, the metallo protein in red blood cells that carries oxygen.
However, in case of Thalassemia when an HLA identical sibling marrow donor is available, the chance of cure is currently as high as 90 percent.
Illustrating the complicated treatment, Dr. Ashish Mukherhjee, Director NCRI, said: "The first step was to destroy all the existing bone marrow cells for which the conditioning chemotheraphy was used. Then the donor's stem cells from two different sources were injected into the patient's body."
"Bone marrow stem cell, on the other hand leads to Graft Versus Host Disese which is triggered by the body's defence mechanism while the transfusion is being done. The two therapies can complement, not only increase the Stem Cell count but also reduce the chance of Graft versus Host disease and lead to a complete cure," Mukherjee said.
The stem cells that were transplanted in the young patient came from his sister's cord blood and bone marrow.
"It was Dr. Asish Mukherjee who gave our child a new life. He told us that our child will get cured and that was the assurance on which we were bagging upon," Ashim Kumar Pal, father of Moinam said.
Dr. Ashish Mukherjee conducted the surgery on Apr 3 to treat a five year old boy named Moinam at the Netaji Subhash Chandra Bose Cancer research Institute in Kolkata.
For conducting this treatment they took the stem cells from the cord blood of the second child (sister of Moinam) of Ashim Pal and Monisha Pal and then preserved it under specified conditions at CordLife, lrgest network of stem cell bank with full processing.
"When stem cells are needed to treat a life threatening disease, doctors ans can effectively predict transplant success by evaluating two factors-HLA compatibility and stem cell count," Prosanto Chowdhury, Medial Director, Cord Life India, said.
"Transplants like these confirm CordLife's technology and our assurance to parents who bank with us their baby's cord blood. HLA matching was undertaken which provided that the tissues of both the children matched and the treatment could proceed. This is the first case of mixed stem cell transplant in India," he said.
Thalassemia is an inherited blood disorder in which the body produces an abnormal form of haemoglobin, the metallo protein in red blood cells that carries oxygen.
However, in case of Thalassemia when an HLA identical sibling marrow donor is available, the chance of cure is currently as high as 90 percent.
Illustrating the complicated treatment, Dr. Ashish Mukherhjee, Director NCRI, said: "The first step was to destroy all the existing bone marrow cells for which the conditioning chemotheraphy was used. Then the donor's stem cells from two different sources were injected into the patient's body."
"Bone marrow stem cell, on the other hand leads to Graft Versus Host Disese which is triggered by the body's defence mechanism while the transfusion is being done. The two therapies can complement, not only increase the Stem Cell count but also reduce the chance of Graft versus Host disease and lead to a complete cure," Mukherjee said.
The stem cells that were transplanted in the young patient came from his sister's cord blood and bone marrow.
"It was Dr. Asish Mukherjee who gave our child a new life. He told us that our child will get cured and that was the assurance on which we were bagging upon," Ashim Kumar Pal, father of Moinam said.
No marriage for Thalassemia couples in Sri Lanka
The Health Ministry will introduce legal provisions to forbid marriages between two Thalassemia carriers to eradicate the disease from Sri Lanka, Health Minister Maithripala Sirisena said.
Minister Sirisena said the ministry has taken measures to make blood tests mandatory for every young couple before marriage.
“If the blood tests do not bring the desired results, the Health Ministry has no option but to bring legislations forbidding marriages between two Thalassemia carriers as Thalassemia is a hereditary disease. Our aim is to eradicate Thalassemia from Sri Lanka by 2015,” Minister Sirisena stressed.
The government spends around Rs. 1.6 billion to treat Thalassemia patients annually and Rs. 350 million out of it is spent only on drugs. If Thalassemia which is a preventable disease could be eradicated, the government can utilize these funds for a better cause, he said.
Some 250,000 marriages are performed annually in Sri Lanka and offspring of 1,600 parents are born with Thalassemia. Latest data shows that there are 1,600 Thalassemia patients in the country and 160 of them are children.
Minister Sirisena said the ministry has taken measures to make blood tests mandatory for every young couple before marriage.
“If the blood tests do not bring the desired results, the Health Ministry has no option but to bring legislations forbidding marriages between two Thalassemia carriers as Thalassemia is a hereditary disease. Our aim is to eradicate Thalassemia from Sri Lanka by 2015,” Minister Sirisena stressed.
The government spends around Rs. 1.6 billion to treat Thalassemia patients annually and Rs. 350 million out of it is spent only on drugs. If Thalassemia which is a preventable disease could be eradicated, the government can utilize these funds for a better cause, he said.
Some 250,000 marriages are performed annually in Sri Lanka and offspring of 1,600 parents are born with Thalassemia. Latest data shows that there are 1,600 Thalassemia patients in the country and 160 of them are children.
4/27/11
Thalassemia cured using cord blood stem cells
R. PRASAD
Eight-year-old Thamirabharuni and her one-year-old brother Pugazhendhi share a special kind of bond not commonly seen among siblings. Thanks to her brother, Thamirabharuni no longer suffers from thalassemia disease.
The stem cells transplanted in March helped her get rid of thalassemia. And hundred days after the procedure, one can safely say that her disease has been cured.
The stem cells that were transplanted came from two different sources — her brother’s cord blood, which was harvested during the time of his birth, and his bone marrow. Stem cells from the bone marrow had to be transplanted as there was insufficient number of stem cells in Pugazhendhi’s cord blood.
In the absence of cord blood stem cells, about 200 ml of bone marrow would have been required. It is difficult to get this quantity of bone marrow from a nine-month-old baby.
The cord blood was collected by and stored at Chennai based LifeCell International Pvt. Ltd., a private cord blood bank.
Risk of infection So is it all over? “One has to be still careful. There is a risk of infection till the end of the first year [after transplantation],” said Dr. Revathy Raj, Consultant Paediatric Haemato Oncologist, Apollo Speciality Hospital, Chennai. Dr. Raj had done the transplantation for Thamirabharuni and two other cord blood transplantations for thalassemia before this.
The fact that patients are on immuno suppressing drugs for one year makes them vulnerable to infections. The risk of rejection of the transplanted stem cells, and the graft versus host disease (GVHD) reduce with time.
Thalassemia arises when red blood corpuscles (RBC) production is defective. A person suffers from the disease only when he inherits a defective gene from both parents. He becomes a carrier when he inherits a defective gene from only one parent. The diseased person has to undergo blood transfusion once every month for the rest of his life.
Gold standard Though stem cells separated from bone marrow have been used for more than 30 years to treat thalassemia, and is a gold standard in treating the disease, cord blood stem cells are slowly becoming an attractive alternative.
Contrary to what is projected by some cord blood banks, doctors are very reluctant to use cord blood stem cells to treat thalassemia in the absence of a full tissue match.
Perfect match “We need a 6/6 [perfect match] for thalassemia. Even a 5/6 match is not sufficient,” asserted Dr. Raj. And doctors refrain from using stem cells from unrelated donors, even if there is a perfect match.
Apart from infections, there are two major challenges from transplantation — graft versus host disease (GVHD) and rejection of the donated stem cells. “There is a 30 per cent chance of having graft versus host disease even when it is from a fully matched related (sibling) donor.” This risk increases to 50 per cent when it is from an unrelated donor, even if there is 6/6 tissue match.
Rejection rate becomes an issue even when there is a perfect tissue match. According to her, in the case of thalassemia, the rejection rate can be up to 20 per cent even with related donors, and up to 40 per cent in the case of unrelated donors.
But why should rejection and GVHD be an issue at all when there is a perfect 6/6 tissue match, and why should it be so high when stem cells are from unrelated donors?
Minor HLAs not tested “There are several minor HLA antigens that are not tested. So if we use stem cells from people belonging to some other ethnic background, there are greater chances of [minor] HLA differences,” Dr. Raj stressed. “And this causes rejection and GVHD.”
In general, greater the tissue match and higher the stem cell count in cord blood, lesser are the chances of rejection and GVHD.
“So why undertake procedures that are risky when thalassemia can be treated through monthly transfusions,” she noted.
Private banking of cord blood for use by the family therefore becomes important when one of the siblings is suffering from a disease that can be cured using it.
Case for public banking Despite the risk of rejection and GVHD, a less than perfect sample can be used to treat children suffering from life threatening diseases such as leukaemia and aplastic anaemia. This is where public cord blood banking gains significance.
There is a strong case for promoting public banks as depending solely on bone marrow samples will not be wise.
Even if a perfectly matched bone marrow donor is found, chances are that the person may no longer be interested in donating.
Collecting cord blood samples is easy, the number of samples that can be banked is limited only by resources, and samples can be made available at very short notice.
| Cord blood and bone marrow stem cells with a perfect tissue match from her one-year-old brother were used for transplantation |
Eight-year-old Thamirabharuni and her one-year-old brother Pugazhendhi share a special kind of bond not commonly seen among siblings. Thanks to her brother, Thamirabharuni no longer suffers from thalassemia disease.
The stem cells transplanted in March helped her get rid of thalassemia. And hundred days after the procedure, one can safely say that her disease has been cured.
The stem cells that were transplanted came from two different sources — her brother’s cord blood, which was harvested during the time of his birth, and his bone marrow. Stem cells from the bone marrow had to be transplanted as there was insufficient number of stem cells in Pugazhendhi’s cord blood.
In the absence of cord blood stem cells, about 200 ml of bone marrow would have been required. It is difficult to get this quantity of bone marrow from a nine-month-old baby.
The cord blood was collected by and stored at Chennai based LifeCell International Pvt. Ltd., a private cord blood bank.
Risk of infection
The fact that patients are on immuno suppressing drugs for one year makes them vulnerable to infections. The risk of rejection of the transplanted stem cells, and the graft versus host disease (GVHD) reduce with time.
Thalassemia arises when red blood corpuscles (RBC) production is defective. A person suffers from the disease only when he inherits a defective gene from both parents. He becomes a carrier when he inherits a defective gene from only one parent. The diseased person has to undergo blood transfusion once every month for the rest of his life.
Gold standard
Contrary to what is projected by some cord blood banks, doctors are very reluctant to use cord blood stem cells to treat thalassemia in the absence of a full tissue match.
Perfect match
Apart from infections, there are two major challenges from transplantation — graft versus host disease (GVHD) and rejection of the donated stem cells. “There is a 30 per cent chance of having graft versus host disease even when it is from a fully matched related (sibling) donor.” This risk increases to 50 per cent when it is from an unrelated donor, even if there is 6/6 tissue match.
Rejection rate becomes an issue even when there is a perfect tissue match. According to her, in the case of thalassemia, the rejection rate can be up to 20 per cent even with related donors, and up to 40 per cent in the case of unrelated donors.
But why should rejection and GVHD be an issue at all when there is a perfect 6/6 tissue match, and why should it be so high when stem cells are from unrelated donors?
Minor HLAs not tested
In general, greater the tissue match and higher the stem cell count in cord blood, lesser are the chances of rejection and GVHD.
“So why undertake procedures that are risky when thalassemia can be treated through monthly transfusions,” she noted.
Private banking of cord blood for use by the family therefore becomes important when one of the siblings is suffering from a disease that can be cured using it.
Case for public banking
There is a strong case for promoting public banks as depending solely on bone marrow samples will not be wise.
Even if a perfectly matched bone marrow donor is found, chances are that the person may no longer be interested in donating.
Collecting cord blood samples is easy, the number of samples that can be banked is limited only by resources, and samples can be made available at very short notice.
2/15/11
Medical leap gives hope to blood disorder sufferers
Gene therapy for the blood disorder beta-thalassemia will be carried out in Thailand for the first time by the end of this year.
A team of doctors at Ramathibodi Hospital is studying the gene therapy technology alongside experts in Paris under a collaboration programme between the Mahidol University led by Prof Suthat Fucharoen and French-American researcher Philippe Leboulch of Harvard Medical School and the University of Paris.The Thai doctors expect to return to Thailand to conduct a trial around December, said Dr Suradej Hongeng, of Ramathibodi Hospital's department of pediatrics.
The collaboration came about after the world's first successful treatment of beta-thalassemia with gene therapy.
A 21-year-old Frenchman treated with the therapy in 2007 now no longer has the need for blood transfusions. He previously had required transfusions every month since birth.
The successful treatment was published in the journal Nature last September.
Beta-thalassemia is caused when a patient cannot produce enough of the beta-globin component of haemoglobin, the protein used by red blood cells to carry oxygen around the body. This can cause life-threatening anaemia, leading to severe damage of the body's major organs.
Gene therapy is generally the insertion, alteration or removal of genes within a patient's cells and biological tissues to treat disease.
"This success justifies the hopes placed in the use of gene therapy to treat blood diseases," said Dr Suradej, a haematology specialist.
"It is also the first time an effective technology has been developed to improve the quality of life for people with thalassemia."
An estimated 20 million Thais are carriers of thalassemia. It is one of the world's most common genetic disorders, putting an enormous financial strain on Thailand and countries located in the "Thalassemia Belt", which stretches from the Mediterranean through the Middle East and Central Asia to Southeast Asia.
About three in 800 children born in Thailand are affected by the severest form of the disorder, beta-thalassemia, requiring regular blood transfusions.
However, blood transfusions carry the risk of contracting HIV and hepatitis B and C from donors, or iron overloading.
The only known cure for the condition is through a bone marrow transplant.
However, this process is dangerous and it can be very difficult to find a matching bone marrow donor, Dr Suradej said.
He hoped the gene therapy for thalassemia treatment would eliminate the problems posed by bone marrow transplants, as well as lead doctors to adapt the technology to treat the symptoms of beta-thalassemia, such as as neurological problems and muscle disabilities.
2/10/11
France's first 'saviour sibling' stirs ethical debate about biotechnology
The country’s first "saviour sibling", a healthy boy whose discarded umbilical cord will help heal one of his two siblings from a genetic blood disease, has brought complicated ethical issues over biotechnology to the forefront in France.
France’s first so-called "saviour sibling" was born in a hospital in the Parisian suburb of Clamart in late January, doctors announced Tuesday. The baby, whose blood stem cells will help cure one of his siblings from a severe genetic blood disease, has also opened a new front in the bioethics debate in France.
Born to parents of Turkish origin and named Umut Talha (Turkish for "our hope"), the child was conceived under circumstances that would have been unthinkable only a generation ago.
Umut Talha’s parents approached the hospital in Clamart a little more than a year ago with a serious problem: their two young children were both afflicted with an inherited blood disorder, Beta thalassemia, which requires monthly blood transfusions. The parents knew the hospital was one of only three in France that was developing a treatment for their children's illness.
An embryo was screened and genetically selected from an original group of 12 embryos. It was picked to ensure it did not carry the gene for Beta thalassemia, but also based on its compatibility with the sick siblings. Besides selecting an offspring that would be spared from the disorder, the parents hoped the future baby would also become a donor of the right kind of treatment cells.
In the end the boy was born disorder-free, and his cells were confirmed to be compatible with his older sister, now aged two. Doctors feel confident that Umut’s sister will be cured with the cells from his discarded umbilical cord, and her monthly blood transfusions will be discontinued.
The family have since returned to their home in southern France, but they plan to return to Clamart to undergo the same procedure to cure their other child, Umut’s four-year-old brother.
Hopes and hurdles
French newspapers spread “medicine baby” across headlines on Tuesday. But speaking at a press conference René Frydman, a fertility pioneer and father of the first French test-tube baby, who also oversaw Umut’s case, said he preferred the term “double-hope baby”.
“Medicine baby is a media term invented by people who are against this kind of procedure,” Frydman told reporters. In English-speaking countries, the terms “donor baby” and “saviour sibling” have been widely used in the media.
For Frydman, Umut represents a double hope for his parents: the hope of having a new, healthy baby, and the hope of curing one of their sick children. But other scientists, religious groups and parents beg to differ.
The issue of saviour babies has raised complex ethical debates, and renewed fears of a move towards “designer babies”, or babies whose traits – such as intelligence, eye-colour and height – have been predetermined.
The timing of Umut's birth could be significant. The very law that allows for cases like Umut’s is being revised starting today. Observers say that the existing legislation guiding biotechnology in France may be tightened and restrict research in certain fields, including stem cells.
The country’s standing bioethics law allows for cases like Umut’s. In fact, the government has earmarked 800,000 euros per year for Clamart to practice and develop the procedure.
But Frydman and his colleagues say a lot more needs to be done, complaining of endless hurdles to launch further research and access funds. They regret that France has started a decade after the United States and that the government is still reluctant to give them its full backing.
France’s first so-called "saviour sibling" was born in a hospital in the Parisian suburb of Clamart in late January, doctors announced Tuesday. The baby, whose blood stem cells will help cure one of his siblings from a severe genetic blood disease, has also opened a new front in the bioethics debate in France.
Born to parents of Turkish origin and named Umut Talha (Turkish for "our hope"), the child was conceived under circumstances that would have been unthinkable only a generation ago.
Umut Talha’s parents approached the hospital in Clamart a little more than a year ago with a serious problem: their two young children were both afflicted with an inherited blood disorder, Beta thalassemia, which requires monthly blood transfusions. The parents knew the hospital was one of only three in France that was developing a treatment for their children's illness.
An embryo was screened and genetically selected from an original group of 12 embryos. It was picked to ensure it did not carry the gene for Beta thalassemia, but also based on its compatibility with the sick siblings. Besides selecting an offspring that would be spared from the disorder, the parents hoped the future baby would also become a donor of the right kind of treatment cells.
In the end the boy was born disorder-free, and his cells were confirmed to be compatible with his older sister, now aged two. Doctors feel confident that Umut’s sister will be cured with the cells from his discarded umbilical cord, and her monthly blood transfusions will be discontinued.
The family have since returned to their home in southern France, but they plan to return to Clamart to undergo the same procedure to cure their other child, Umut’s four-year-old brother.
Hopes and hurdles
French newspapers spread “medicine baby” across headlines on Tuesday. But speaking at a press conference René Frydman, a fertility pioneer and father of the first French test-tube baby, who also oversaw Umut’s case, said he preferred the term “double-hope baby”.
“Medicine baby is a media term invented by people who are against this kind of procedure,” Frydman told reporters. In English-speaking countries, the terms “donor baby” and “saviour sibling” have been widely used in the media.
For Frydman, Umut represents a double hope for his parents: the hope of having a new, healthy baby, and the hope of curing one of their sick children. But other scientists, religious groups and parents beg to differ.
The issue of saviour babies has raised complex ethical debates, and renewed fears of a move towards “designer babies”, or babies whose traits – such as intelligence, eye-colour and height – have been predetermined.
The timing of Umut's birth could be significant. The very law that allows for cases like Umut’s is being revised starting today. Observers say that the existing legislation guiding biotechnology in France may be tightened and restrict research in certain fields, including stem cells.
The country’s standing bioethics law allows for cases like Umut’s. In fact, the government has earmarked 800,000 euros per year for Clamart to practice and develop the procedure.
But Frydman and his colleagues say a lot more needs to be done, complaining of endless hurdles to launch further research and access funds. They regret that France has started a decade after the United States and that the government is still reluctant to give them its full backing.
Researchers report gene therapy strategy that improves Beta Thalassemia in mice model
Researchers at Nationwide Children's Hospital report a gene therapy strategy that improves the condition of a mouse model of an inherited blood disorder, Beta Thalassemia. The gene correction involves using unfertilized eggs from afflicted mice to produce a batch of embryonic stem cell lines. Some of these stem cell lines do not inherit the disease gene and can thus be used for transplantation-based treatments of the same mice. Findings could hold promise for a new treatment strategy for autosomal dominant diseases like certain forms of Beta Thalassemia, tuberous sclerosis or Huntington's disease.
Embryonic stem cells have the potential to produce unlimited quantities of any cell type and are therefore being explored as a new therapeutic option for many diseases. Unfertilized eggs can be cultured to form embryonic stem cells, so-called parthenogenetic embryonic stem cells.
"Parthenogenetic embryonic stem cells can differentiate into multiple tissue types as do stem cells from fertilized embryos," said K. John McLaughlin, PhD, principal investigator in the Center for Molecular and Human Genetics at The Research Institute at Nationwide Children's Hospital. Previously, the group demonstrated that blood cells derived from parthenogenetic cells could provide healthy, long-term blood replacement in mice.
"Advantages of parthenogenetic stem cells are not only that fertilization is not needed, but also that the recipient's immune system may potentially not view them as foreign, minimizing rejection problems. Furthermore, since parthenogenetic embryonic stem cells are derived from reproductive cells which contain only a single set of the genetic information instead of the double set present in body cells, they may not contain certain abnormal genes present in the other copy," said Dr. McLaughlin also one of the study authors.
Embryonic stem cells have the potential to produce unlimited quantities of any cell type and are therefore being explored as a new therapeutic option for many diseases. Unfertilized eggs can be cultured to form embryonic stem cells, so-called parthenogenetic embryonic stem cells.
"Parthenogenetic embryonic stem cells can differentiate into multiple tissue types as do stem cells from fertilized embryos," said K. John McLaughlin, PhD, principal investigator in the Center for Molecular and Human Genetics at The Research Institute at Nationwide Children's Hospital. Previously, the group demonstrated that blood cells derived from parthenogenetic cells could provide healthy, long-term blood replacement in mice.
"Advantages of parthenogenetic stem cells are not only that fertilization is not needed, but also that the recipient's immune system may potentially not view them as foreign, minimizing rejection problems. Furthermore, since parthenogenetic embryonic stem cells are derived from reproductive cells which contain only a single set of the genetic information instead of the double set present in body cells, they may not contain certain abnormal genes present in the other copy," said Dr. McLaughlin also one of the study authors.
A single copy of an abnormal gene inherited from one parent can cause so-called autosomal dominant diseases such as tuberous sclerosis or Huntington's disease. The affected person has one defective and one normal copy of the gene, but the abnormal gene overrides the normal gene, causing disease. In normal sexual reproduction, each parent provides one gene copy to offspring via their reproductive cells. Therefore, the reproductive cells of a patient with an autosomal dominant disease could either pass along a defective copy or a normal copy.
"As the donor patient has one defective gene copy and one normal, and only one copy is used for normal reproduction, we can select egg-cell-derived embryonic stem cells with two normal copies," said Dr. McLaughlin. "These single-parent/patient-derived embryonic stem cells can theoretically be used for correction of a diverse number of diseases that occur when one copy of the gene is abnormal," said Dr. McLaughlin.
To test this theory, Dr. McLaughlin and colleagues from the University of Pennsylvania, University of North Carolina and University of Minnesota, examined whether parthenogenetic embryonic stem cells could be used for tissue repair in a mouse model of thalassemia intermedia. Thalassemia intermedia is an inherited blood disorder in which the body lacks sufficient normal hemoglobin, leading to excessive destruction of red blood cells and anemia. They used a mouse model in which one defective gene copy causes anemia.
Using approaches developed from a previous study done by this group, Nationwide Children's Research Fellow Sigrid Eckardt, PhD, derived embryonic stem cells from the unfertilized eggs of female mice with the disease, and identified those stem cell lines that contained only the "healthy" hemoglobin genes. These "genetically clean" embryonic stem cell lines were converted into cells that were transplanted into afflicted mice that were carriers of the disease causing gene. Blood samples drawn five weeks after transplantation revealed that the delivered cells were present in the recipients' blood. Their red blood cells were also corrected to a size similar to normal mice and red blood cell count, hematocrit and hemoglobin levels became normal.
"Overall, we observed long-term improvement of thalassemia in this model," said Dr. Eckardt. "Our findings suggest that using reproductive cells to generate embryonic stem cells that are 'disease-free' may be a solution for genetic diseases involving large, complex or poorly identified deletions in the genome or that are not treatable by current gene therapy approaches." Dr. McLaughlin says that this approach also contrasts with typical gene therapy approaches in that it requires no engineering of the genome, which is currently difficult to achieve in human embryonic and embryonic-like (IPS) stem cells.
Source: Nationwide Children's Hospital
"As the donor patient has one defective gene copy and one normal, and only one copy is used for normal reproduction, we can select egg-cell-derived embryonic stem cells with two normal copies," said Dr. McLaughlin. "These single-parent/patient-derived embryonic stem cells can theoretically be used for correction of a diverse number of diseases that occur when one copy of the gene is abnormal," said Dr. McLaughlin.
To test this theory, Dr. McLaughlin and colleagues from the University of Pennsylvania, University of North Carolina and University of Minnesota, examined whether parthenogenetic embryonic stem cells could be used for tissue repair in a mouse model of thalassemia intermedia. Thalassemia intermedia is an inherited blood disorder in which the body lacks sufficient normal hemoglobin, leading to excessive destruction of red blood cells and anemia. They used a mouse model in which one defective gene copy causes anemia.
Using approaches developed from a previous study done by this group, Nationwide Children's Research Fellow Sigrid Eckardt, PhD, derived embryonic stem cells from the unfertilized eggs of female mice with the disease, and identified those stem cell lines that contained only the "healthy" hemoglobin genes. These "genetically clean" embryonic stem cell lines were converted into cells that were transplanted into afflicted mice that were carriers of the disease causing gene. Blood samples drawn five weeks after transplantation revealed that the delivered cells were present in the recipients' blood. Their red blood cells were also corrected to a size similar to normal mice and red blood cell count, hematocrit and hemoglobin levels became normal.
"Overall, we observed long-term improvement of thalassemia in this model," said Dr. Eckardt. "Our findings suggest that using reproductive cells to generate embryonic stem cells that are 'disease-free' may be a solution for genetic diseases involving large, complex or poorly identified deletions in the genome or that are not treatable by current gene therapy approaches." Dr. McLaughlin says that this approach also contrasts with typical gene therapy approaches in that it requires no engineering of the genome, which is currently difficult to achieve in human embryonic and embryonic-like (IPS) stem cells.
Source: Nationwide Children's Hospital
Subscribe to:
Posts (Atom)