Donor Peripheral Stem Cell Transplant in Treating Patients With Advanced Hematologic Cancer or Other Disorders

OBJECTIVES:

Primary

• To evaluate hematopoietic recovery, using neutrophil and platelet engraftment as the primary criterion, in patients with advanced hematologic malignancies or other disorders undergoing allogeneic peripheral blood stem cell (PBSC) transplantation from matched unrelated donors.
• To evaluate the incidence of acute and chronic graft-versus-host-disease (GVHD) in patients undergoing allogeneic PBSC transplantation from matched unrelated donors.

Secondary

• To evaluate the impact of HLA class I and class II allele-matching on the incidence of GVHD and on the survival outcome of these patients.
• To evaluate overall survival, disease-free survival, and relapse in these patients.

OUTLINE: Patients are stratified according to type of conditioning regimen (myeloablative vs reduced-intensity myeloablative). Patients are assigned to a conditioning regimen according to diagnosis, age, disease status, prior radiotherapy, and prior autologous stem cell transplantation.

• Conditioning regimen:

• Regimen I: Patients undergo total body irradiation (TBI) on days -7 to -4 and receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1.
• Regimen II: Patients receive busulfan IV over 2 hours once on day -8 and then every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days -3 and -2.
• Regimen III: Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.
• Regimen IV: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.
• Regimen V: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
• Regimen VI: Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.
• Allogeneic peripheral blood stem cell (PBSC) transplantation: All patients undergo allogeneic PBSC transplantation on day 0.
• Graft-versus-host disease (GVHD) prophylaxis: Patients receive one of the following GVHD prophylaxis regimens:

• Regimen A: Patients receive tacrolimus IV or orally on days -1 to 180 and methotrexate IV on days 1, 3, 6, and 11.
• Regimen B: Patients receive cyclosporine IV or orally twice daily on days -1 to 180, mycophenolate mofetil IV over 2 hours or orally twice daily on days 0-27, and methotrexate IV on days 1, 3, and 6.
• Regimen C: Patients receive tacrolimus IV continuously or orally, and oral sirolimus beginning on day -3. Patients also receive methotrexate IV on days 1, 3, and 6.

After completion of study therapy, patients are followed periodically.

DISEASE CHARACTERISTICS:

• Diagnosis of one of the following:

• Acute lymphocytic leukemia (ALL), meeting one of the following criteria:

• In first relapse or beyond
• High-risk ALL, defined by any of the following:

• Hypoploidy (≤ 44 chromosomes)
• Pseudodiploidy with translocations or molecular evidence of t(9;22), 11q23, or t(8;14), excluding B-cell ALL
• Elevated WBC at presentation (WBC > 20,000/mm³ [for patients > 18 years of age]; WBC > 200,000/mm³ [for patients 12-18 years of age])
• Acute myeloid leukemia (AML), meeting one of the following criteria:

• In first complete remission
• Failed to achieve remission
• In first relapse or beyond
• Secondary AML (> 30% blasts in marrow aspirate)

• Should receive induction chemotherapy to obtain remission, if possible, before transplant
• Chronic myelogenous leukemia, meeting one of the following criteria:

• In first or second chronic phase or accelerated phase
• In blast crisis, defined as > 30% promyelocytes plus blasts in the bone marrow
• Myelodysplastic syndromes, including any of the following:

• Refractory anemia with excess blasts (RAEB)
• Chronic myelomonocytic leukemia
• RAEB in transformation
• Refractory non-Hodgkin lymphoma, chronic lymphocytic leukemia, Hodgkin lymphoma, or multiple myeloma

• Received and failed front-line therapy, high-dose therapy and autologous stem cell transplantation, or salvage therapy
• Myeloproliferative disorders/myelofibrosis may be allowed on a case by case basis
• Severe aplastic anemia, paroxysmal nocturnal hemoglobinuria, or any other hematologic disorder requiring transplantation
• Patients > 55 years of age with hematologic diseases treatable by allogeneic stem cell transplantation who are not eligible for IRB 99190 are eligible
• No uncontrolled CNS involvement of disease
• No matched (6/6) related donor available
• HLA-identical unrelated donor available

• HLA-phenotypically identical for HLA-A and HLA-B alleles and identical for DRB1 alleles by DNA typing for both class I and class II antigens

• Allele mismatch for HLA class I (i.e., B 2701 vs B 2702) allowed if no alternative donors
• Allele mismatch for class II (i.e., DRB1 0401 vs 0402) or minor mismatch for class I cross reactive group (CREG) (i.e., A 2 vs A 28) allowed in patients ≤ 35 years of age requiring urgent transplant

PATIENT CHARACTERISTICS:

• Karnofsky performance status 50-100%
• Life expectancy > 8 weeks
• LVEF ≥ 45% at rest
• AST ≤ 2 times normal (unless liver function abnormality is due to underlying disease)
• Total bilirubin < 1.5 times normal (unless liver function abnormality is due to underlying disease)
• Creatinine ≤ 1.5 times normal OR creatinine clearance ≥ 60 mL/min
• DLCO ≥ 40% of predicted (corrected for hemoglobin)
• No coexisting medical problem that would significantly increase the risk of the transplant procedure
• HIV negative
• Not pregnant

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics