Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders
Congenital Amegakaryocytic Thrombocytopenia, Diamond-blackfan Anemia, Leukemia
About this trial
This is an interventional treatment trial for Congenital Amegakaryocytic Thrombocytopenia focused on measuring de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, childhood acute myeloid leukemia in remission, childhood chronic myelogenous leukemia, congenital amegakaryocytic thrombocytopenia, Diamond-Blackfan anemia, severe congenital neutropenia, secondary acute myeloid leukemia, chronic phase chronic myelogenous leukemia, childhood myelodysplastic syndromes
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of 1 of the following hematologic conditions: Aplastic anemia with marrow aplasia, meeting all of the following criteria: Absolute neutrophil count < 500/mm^3 Platelet and/or red cell transfusion dependent Chronic aplastic anemia, meeting all of the following criteria: Transfusion dependent Unresponsive to immunosuppressive therapy Alternative matched unrelated donor has been identified Congenital marrow failure syndrome, including any of the following (with closely matched related or unrelated donor): Primary red cell aplasia (Diamond-Blackfan syndrome) Congenital neutropenia (Kostmann's syndrome) Amegakaryocytic thrombocytopenia Congenital dyserythropoietic anemias Other severe acquired cytopenias in which a transplantation using a combined busulfan/cyclophosphamide conditioning regimen is indicated Hemoglobinopathy (with closely matched related or unrelated donor) β-thalassemia major Sickle cell anemia Hemoglobin E/β-thalassemia Severe immunodeficiency disease Chediak-Higashi disease Wiskott-Aldrich syndrome Combined immunodeficiency disease (Nezelof's) Hyper immunoglobulin M (IgM) syndrome Bare lymphocyte syndrome Chronic granulomatous disease Familial erythrohemophagocytic lymphohistiocytosis Other stem cell defects (e.g., osteopetrosis) Severe immune dysregulation/autoimmune disorders Achieved a transient response to prior immunosuppressive therapy Chronic myelogenous leukemia Disease in first chronic phase Acute myeloid leukemia Disease in first remission Myelodysplastic syndromes Inborn errors of metabolism Histiocytosis No severe combined immunodeficiency disease Matched related or unrelated donor available by high resolution DNA typing Related donor, meeting both of the following criteria: Matched at both human leukocyte antigen (HLA)-Drβ1 alleles No more than 1 mismatch at the 4 HLA-A and -B alleles Unrelated donor, meeting 1 of the following criteria: Marrow matched at both HLA-Drβ1 alleles AND no more than 1 mismatch at the 4 HLA-A and -B alleles Umbilical cord blood matched at 5/6 HLA-A, -B, and -DRβ1 alleles with at least 1 -DRβ1 match AND there are ≥ 3x10^5 CD34+ (Cluster of differentiation 34-positive) cells per kg body weight of recipient available at the time of cryopreservation PATIENT CHARACTERISTICS: Cardiac ejection fraction ≥ 27% Creatinine clearance ≥ 50 mL/min by 24-hour urine collection or glomerular filtration rate DLCO (diffusion capacity of lung for carbon monoxide) ≥ 50% of predicted (corrected for anemia/lung volume) PRIOR CONCURRENT THERAPY: No prior transplantation for leukemia from which patient remains engrafted and alemtuzumab is not needed as part of the conditioning regimen
Sites / Locations
- UCSF Helen Diller Family Comprehensive Cancer Center
- University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Arms of the Study
Arm 1
Experimental
Single arm - conditioning and transplant
Alemtuzumab 0.5 mg/kg (maximum 15 mg) daily for 3 days; Busulfan i.v. every 6 hours from day -9 to day -6 for 16 total doses; Fludarabine phosphate from day -5 for 4 days at 1.3 mg/kg (if patient was less than 12 kg) or 40 mg/m*2 per dose; Cyclosporine continuous infusion 3 mg/kg/Day beginning day -1 for GVHD prophylaxis; Methotrexate at 15 mg/m*2 on day +1, 10 mg/m*2 on days +3, +6, and (only for MUDs) day +11 also for GVHD prophylaxis; Methylprednisolone only as required for GVHD prophylaxis; allogeneic bone marrow transplantation or allogeneic hematopoietic stem cell transplantation or peripheral blood stem cell transplantation or umbilical cord blood transplantation.