Long Term Outcomes in β Thalassemia Major
| Status: | Recruiting |
|---|---|
| Conditions: | Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | Any - 30 |
| Updated: | 4/2/2016 |
| Start Date: | June 2014 |
| End Date: | June 2016 |
| Contact: | Colleen E Rosen, RN, BS |
| Email: | crosen@luriechildrens.org |
| Phone: | 312-227-4870 |
Long Term Outcomes in β Thalassemia Major - Comparing Late Outcomes Following Allogeneic Hematopoietic Stem Cell Transplantation and Standard Supportive Care
Beta thalassemia (β-thalassemia) is the most common genetic disease worldwide. Individuals
with thalassemia are born with a defect in hemoglobin. Hemoglobin is a protein in red blood
cells that carries oxygen to vital organs such as the brain, heart, lungs and kidneys.
Thalassemia major is a hereditary anemia characterized by little or no ß-globin production,
which results in hemolysis (breakdown or destruction of red blood cells) due to the
formation of unstable alpha-globin tetramers and ineffective erythropoiesis which is
uniformly fatal in the absence of regular transfusions. Although improvements in
conservative treatment have improved the prognosis of thalassemia considerably disease and
transfusion related complications in affected patients progress over time, causing severe
morbidity and shortened life expectancy. Substantial lifelong health care expenses are also
involved, often a financial burden for families and unsustainable in most developing
countries.
The hypothesis is that patients who had beta thalassemia who have undergone a hematopoietic
stem cell transplant (HSCT) and are >1 year post-HSCT will have less long term comorbidities
and a higher quality of life (QOL) as compared to those with beta thalassemia who are
maintained on supportive care. In order to assess quality of life, a quality of life
questionnaire will be asked. Extraction of data from the patient's medical record will also
be used to determine any comorbidities that have occurred after either a HSCT or supportive
care therapy.
with thalassemia are born with a defect in hemoglobin. Hemoglobin is a protein in red blood
cells that carries oxygen to vital organs such as the brain, heart, lungs and kidneys.
Thalassemia major is a hereditary anemia characterized by little or no ß-globin production,
which results in hemolysis (breakdown or destruction of red blood cells) due to the
formation of unstable alpha-globin tetramers and ineffective erythropoiesis which is
uniformly fatal in the absence of regular transfusions. Although improvements in
conservative treatment have improved the prognosis of thalassemia considerably disease and
transfusion related complications in affected patients progress over time, causing severe
morbidity and shortened life expectancy. Substantial lifelong health care expenses are also
involved, often a financial burden for families and unsustainable in most developing
countries.
The hypothesis is that patients who had beta thalassemia who have undergone a hematopoietic
stem cell transplant (HSCT) and are >1 year post-HSCT will have less long term comorbidities
and a higher quality of life (QOL) as compared to those with beta thalassemia who are
maintained on supportive care. In order to assess quality of life, a quality of life
questionnaire will be asked. Extraction of data from the patient's medical record will also
be used to determine any comorbidities that have occurred after either a HSCT or supportive
care therapy.
Hematopoietic stem cell transplantation (HSCT) is considered a suitable alternative to
conservative management which includes chronic transfusion therapy, iron chelation (iron
overload) and management of complications of transfusion therapy and iron overload. Barriers
to HSCT considerations include risks inherent to transplant- early mortality, graft versus
host disease (GVHD), graft rejection, infections prior to immune reconstitution, and
transplant related organ toxicities. As in supportive care, significant progress has been
made in HSCT for thalassemia has been made over the last 3 decades. This has resulted in
disease-free survival (DFS) rates exceeding 80% especially in young, low-risk patients with
histocompatible (same gene) family donors and more recently even in unrelated donor
transplants following streamlining of preparative regimen and improvements in post-HSCT
supportive care.
Lucarelli and his colleagues at Pesaro initially pioneered HSCT in thalassemia and described
a standard "Pesaro" risk stratification scheme based on liver size by physical examination,
fibrosis detected on liver biopsy, and chelation history. This has been used for years to
risk stratify patients before HSCT and has been shown to correlate well with immediate
transplantation outcomes. More recently reports from the Center for International Blood and
Marrow Transplant Research (CIBMTR) and from the Asian sub-continent on results of Human
Leukocyte Antigen (HLA) -matched sibling HSCT for thalassemia major confirmed that age at
transplantation and liver size are independent predictors of mortality after
transplantation. In patients aged <7 years and without hepatomegaly (liver palpated <2 cm
below the costal margin), the 5-year probabilities of Overall Survival (OS) and DFS were 98%
and 94%, respectively (ref). Morbidity in thalassemia patients (both transplant related and
non-transplanted) is attributed to iron overload associated end organ damage. Although there
is data on long term outcomes in chronically transfused thalassemia patients, the data on
long-term outcomes after HSCT for thalassemia remains limited.
Some patients undergo hematopoietic stem cell transplantation (HSCT) in hopes to cure
themselves of Beta-Thalassemia. Other patients manage their Beta-Thalassemia with supportive
care including chronic blood transfusions, iron chelation and medications. The purpose of
this study is to compare how patients with Beta-Thalassemia are doing after HSCT versus
those patients who manage their Beta-Thalassemia with supportive care. This proposal aims to
compare long term outcomes in thalassemia patients that have survived a HSCT for thalassemia
and compare it with the age and sex matched patients who have remained on transfusion
therapy with regular chelation. In order to compare these two subsets of patients, data will
be obtained from the Thalassemia Longitudinal Cohort (TLC) study.
conservative management which includes chronic transfusion therapy, iron chelation (iron
overload) and management of complications of transfusion therapy and iron overload. Barriers
to HSCT considerations include risks inherent to transplant- early mortality, graft versus
host disease (GVHD), graft rejection, infections prior to immune reconstitution, and
transplant related organ toxicities. As in supportive care, significant progress has been
made in HSCT for thalassemia has been made over the last 3 decades. This has resulted in
disease-free survival (DFS) rates exceeding 80% especially in young, low-risk patients with
histocompatible (same gene) family donors and more recently even in unrelated donor
transplants following streamlining of preparative regimen and improvements in post-HSCT
supportive care.
Lucarelli and his colleagues at Pesaro initially pioneered HSCT in thalassemia and described
a standard "Pesaro" risk stratification scheme based on liver size by physical examination,
fibrosis detected on liver biopsy, and chelation history. This has been used for years to
risk stratify patients before HSCT and has been shown to correlate well with immediate
transplantation outcomes. More recently reports from the Center for International Blood and
Marrow Transplant Research (CIBMTR) and from the Asian sub-continent on results of Human
Leukocyte Antigen (HLA) -matched sibling HSCT for thalassemia major confirmed that age at
transplantation and liver size are independent predictors of mortality after
transplantation. In patients aged <7 years and without hepatomegaly (liver palpated <2 cm
below the costal margin), the 5-year probabilities of Overall Survival (OS) and DFS were 98%
and 94%, respectively (ref). Morbidity in thalassemia patients (both transplant related and
non-transplanted) is attributed to iron overload associated end organ damage. Although there
is data on long term outcomes in chronically transfused thalassemia patients, the data on
long-term outcomes after HSCT for thalassemia remains limited.
Some patients undergo hematopoietic stem cell transplantation (HSCT) in hopes to cure
themselves of Beta-Thalassemia. Other patients manage their Beta-Thalassemia with supportive
care including chronic blood transfusions, iron chelation and medications. The purpose of
this study is to compare how patients with Beta-Thalassemia are doing after HSCT versus
those patients who manage their Beta-Thalassemia with supportive care. This proposal aims to
compare long term outcomes in thalassemia patients that have survived a HSCT for thalassemia
and compare it with the age and sex matched patients who have remained on transfusion
therapy with regular chelation. In order to compare these two subsets of patients, data will
be obtained from the Thalassemia Longitudinal Cohort (TLC) study.
Inclusion for those who underwent HSCT:
- Age 0 to 30 years of age
- >1 year post-allogeneic HSCT for Beta-Thalassemia. Any donor (sibling or unrelated)
and any donor source (bone marrow, peripheral blood, umbilical cord blood) is
considered eligible. Any conditioning regimen is considered acceptable for enrollment
Exclusion:
- <1 year post-allogeneic HSCT for Beta-Thalassemia
- Patient expired prior to 1 year post-HSCT
- Autologous stem cell transplantation for Beta-Thalassemia
We found this trial at
1
site
225 E Chicago Ave
Chicago, Illinois 60611
Chicago, Illinois 60611
(312) 227-4000
Ann & Robert H. Lurie Children's Hospital of Chicago Ann & Robert H. Lurie Children
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