hsct for patients with high risk hemoglobinopathies using reduced intensity

Conditions: Sickle Cell Disease; Beta Thalassemia-Major

Summary: this study will evaluate the use of reduced intensity conditioning regimen in patients with high risk hemoglobinopathy sickle cell and b-thalassemia major in combination with standard immunosuppressive medications, followed by a routine stem cell transplant in order to assess whether or not it is as effective as myeloablative high dose chemotherapy and transplant.

standard myeloablative regimens are toxic to non-hematopoietic tissue and are associated with treatment related mortality and morbidity (trm). preparative regimens that are not myeloablative are associated with a greatly decreased incidence of trm. in addition to providing a less toxic regimen, the reduced intensity chemotherapy preparative regimen also remains immunosuppressive enough to allow donor engraftment. recent report of non-myeloablative regimens which resulted in engraftment of allogeneic stem cell in hematological malignancies raises the possibility that this conditioning regimen might be useful in achieving engraftment in non hematological disorder. in an effort to achieve stable engraftment with any suitable donor stem cell source and to minimize toxicity the investigators have developed a new reduced intensity conditioning regimen for high risk hemoglobinopathies with the main aim of significantly suppressing the recipient's immune system and facilitate engraftment. non-myeloablative or reduced-intensity immunosuppressive preparative regimens have achieved a stable, mixed chimerism engraftment and successful allogeneic bone marrow transplants.

Eligibility criteria:
inclusion criteria: * patient inclusion criteria for sickle cell disease * patients at least one year of age to less than or equal to 21 years of age with (sickle cell disease-ss or sickle cell-s-β-thalassemia and with one or more of the following disease complications: * development of stroke on chronic transfusion protocol. * allosensitization on chronic transfusion therapy * impaired neuropsychological function and abnormal mri scan * abnormal transcranial doppler studies * acute chest syndrome (2 to 3 episodes of acute chest syndrome in last 3 to 4 years). * ferritin level \< 1500 mg/ml * recurrent painful priapism; 3-4 episodes/year requiring intervention. * recurrent vaso-occlusive crisis of at least 3 to 4 episodes/year. * osteonecrosis of multiple bones with documented destructive changes. * signed informed consent * patients physically and psychologically capable of undergoing transplantation and a period of strict isolation. * ferritin \< 1500 * liver iron concentration \< 6mg/g patient inclusion criteria for β thalassemia major patients less than or equal to 21 years of age with b- thalassemia major on routine monthly transfusion protocol or with one or more of the following complications; 1. hepatomegaly. 2. liver biopsy revealing evidence of portal fibrosis as a) mild b) moderate 3. ferritin level≤ 1500ng/ml 4. liver iron concentration (lic) \< 6mg/g exclusion criteria: * exclusion criteria for both sickle cell and β thalassemia major patient * hiv positive result confirmed by western blot. * pregnancy (pregnancy testing for females of child-bearing age will be performed and those with a positive serum β-human chorionic gonadotropin will be excluded) and lactating females. * creatinine greater than two times the upper limit of normal for the laboratory, * pulmonary disease with fvc, fev1 or dlco parameters \< 50% predicted (corrected for hemoglobin) or stage 3 or 4 sickle lung disease. * cardiac insufficiency or coronary artery disease requiring treatment * active infection requiring systemic antibiotic therapy with antibacterial, antifungal or antiviral agents * lansky performance score \<70%- (appendix b) * acute hepatitis/biopsy evidence of cirrhosis. * pulmonary hypertension

Keywords: reduced intensity conditioning regimen