T-cell Depleted Bone Marrow and G-CSF Stimulated Peripheral Stem Cell Transplantation From Related Donors in Treating Patients With Leukemia, Lymphoblastic Lymphoma, Myelodysplastic Syndrome, or Aplastic Anemia
Leukemia, Lymphoma, Myelodysplastic Syndromes
About this trial
This is an interventional treatment trial for Leukemia focused on measuring recurrent childhood acute lymphoblastic leukemia, stage IV childhood lymphoblastic lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent childhood acute myeloid leukemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, relapsing chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, adult acute myeloid leukemia in remission, adult acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, childhood acute lymphoblastic leukemia in remission, stage IV adult lymphoblastic lymphoma, recurrent adult lymphoblastic lymphoma, secondary acute myeloid leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, juvenile myelomonocytic leukemia, childhood chronic myelogenous leukemia, atypical chronic myeloid leukemia, BCR-ABL1 negative, myelodysplastic/myeloproliferative neoplasm, unclassifiable, chronic myelomonocytic leukemia, childhood myelodysplastic syndromes
Eligibility Criteria
DISEASE CHARACTERISTICS: One of the following diagnoses: Acute myelogenous leukemia (AML) meeting 1 of the following conditions: Failed to achieve first remission after an intensive induction regimen containing an anthracycline and cytarabine In second remission and not enrolled in a protocol for autologous bone marrow transplantation Failed to achieve or sustain second remission In first remission but at high risk of relapse because of 1 of the following factors: High-risk cytogenetic features (monosomy 7,5q-, trisomy 8, or t(9;22)) AML secondary to treatment of a prior malignancy and without good-risk cytogenetic features of t(8;21), t(15;17), or inv 16 AML secondary to myelodysplastic disease Acute lymphocytic leukemia (ALL) meeting 1 of the following conditions: In second remission with initial relapse occurring within 2 years of diagnosis In first complete remission with high-risk cytogenetics (t(9;22) or t(4;11)) In third or subsequent remission Failed to achieve or sustain a second remission Chronic myelogenous leukemia (CML) in first or second chronic phase or accelerated phase Stage IV lymphoblastic lymphoma not in first remission or that failed to achieve a remission within the first 4 weeks of induction therapy Juvenile CML Myelodysplastic syndrome Severe aplastic anemia unresponsive to anti-thymocyte globulin or cyclosporine No CNS or skin involvement with leukemia No requirement for mediastinal irradiation No healthy, HLA-identical related donor of at least 1 year of age or matched unrelated donor available within 4-6 months Availability of a healthy, 1-3 HLA-A, -B, and -DR mismatched related donor Willing and able to undergo general anesthesia for marrow donation and a 5-day course of filgrastim (G-CSF) with 2 daily leukaphereses PATIENT CHARACTERISTICS: Age: Under 50 (50 and over allowed on a case-by-case basis) Performance status: Age 16 and over: Karnofsky 70-100% Under age 16: Lansky 50-100% Hematopoietic: Not specified Hepatic: Bilirubin less than 2.0 mg/dL (in the absence of liver involvement) AST less than twice normal (in the absence of liver involvement) Renal: Creatinine normal OR Creatinine clearance greater than 60 mL/min Cardiovascular: Asymptomatic or LVEF greater than 50% at rest, with improvement during exercise Pulmonary: Asymptomatic or DLCO greater than 50% predicted (corrected for hemoglobin) Other: No known hypersensitivity to mouse protein or chicken egg products No active viral, bacterial, or fungal infection HIV-1, HIV-2, HTLV-1, and HTLV-2 negative No other concurrent medical condition that would preclude transplantation Not pregnant or nursing PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy See Disease Characteristics Surgery See Disease Characteristics
Sites / Locations
- Memorial Sloan-Kettering Cancer Center
Arms of the Study
Arm 1
Experimental
Candidates for transplant
Pts stratified by number of HLA-incompatible alleles(1 vs 2 or 3). Harvest:Begin 6-10 d before transplant,allogeneic BM is harvest & tx in vitro. Begin 5-6 d before transplant,G-CSF-stimulated,PBSC harvest,selected for CD34+ cells,& treatment in vitro. If doable,ABM harvest in event of allogeneic graft failure. Myeloablation:Pts u/g TBI 3x d days -9 to -6, thiotepa IV over 4hrs days -5 & -4, & cyclophosphamide IV days -3 & -2. Transplant:CD34+, E-rosette & T-cell-depleted PBSC infuse over 15mins & T-cell-depleted bone marrow infused over 1-5mins day 0. Pts get G-CSF IV over 30 min begin day 1 & continue til blood counts recover & tapering. Pts get anti-thymocyte globulin IV over 4-6hrs days 8,10,12,&14 & oral methylprednisolone days 8-14 followed by tapered doses days 15-17. See detailed description for more details.