Combination Chemotherapy and Antithymocyte Globulin in Reducing Graft-Versus-Host Disease in Patients Undergoing Donor Stem Cell Transplantation For Myelodysplastic Syndrome or Myeloproliferative Disorder

Combination Chemotherapy and Antithymocyte Globulin in Reducing Graft-Versus-Host Disease in Patients Undergoing Donor Stem Cell Transplantation For Myelodysplastic Syndrome or Myeloproliferative Disorder

Conditioning With Targeted Busulfan, Cyclophosphamide and Thymoglobulin for Allogeneic Marrow or Peripheral Blood Stem Cell (PBSC) Transplantation for Myelodysplasia and Myeloproliferative Disorders

RATIONALE: Combining antithymocyte globulin with combination chemotherapy before donor peripheral stem cell transplantation may reduce the chance of developing graft-versus-host disease following transplantation. PURPOSE: Phase I/II trial to study the effectiveness of combining antithymocyte globulin with busulfan and cyclophosphamide in reducing graft-versus-host disease in patients who are undergoing donor stem cell transplantation for myelodysplastic syndrome or other myeloproliferative disorder.

OBJECTIVES: Determine the incidence of acute graft-vs-host disease (GVHD) requiring therapy in patients with myelodysplastic syndromes or myeloproliferative disorders treated with busulfan, cyclophosphamide, and anti-thymocyte globulin prior to transplantation with filgrastim (G-CSF)-mobilized peripheral blood stem cells (or bone marrow) from related or unrelated donors. Determine the incidence of relapse and relapse-free survival in patients treated with this regimen. Determine the incidence of non-relapse mortality by day 100 and 1 year posttransplantation in patients treated with this regimen. Determine the incidence of Epstein-Barr virus reactivation, infections, and chronic GVHD in patients treated with this regimen. OUTLINE: This is a dose-escalation study of anti-thymocyte globulin. Conditioning and graft-vs-host disease (GVHD) prophylaxis: Patients receive oral busulfan every 6 hours on days -7 to -4 (16 doses), cyclophosphamide IV on days -3 and -2, and anti-thymocyte globulin IV over 3 hours on days -3, -2, and -1. Cohorts of 15 patients receive adjusted doses of anti-thymocyte globulin to determine the optimal dose at which Epstein-Barr virus (EBV) activation and GVHD are reduced. The optimal dose is the dose at which 2 consecutive cohorts receive the same regimen. Stem cell transplantation: Patients undergo peripheral blood stem cell (PBSC) or bone marrow transplantation on day 0. Posttransplantation GVHD prophylaxis: Patients receive cyclosporine IV continuously on days -1 to 4 and then orally twice daily until day 180. Patients also receive methotrexate on days 1, 3, 6, and 11. Patients are followed every 6 months for 2 years and then annually thereafter. PROJECTED ACCRUAL: A total of 30-45 patients will be accrued for this study within 2 years.

Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

graft versus host disease, polycythemia vera, chronic idiopathic myelofibrosis, essential thrombocythemia, untreated adult acute myeloid leukemia, recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, untreated childhood acute myeloid leukemia and other myeloid malignancies, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, chronic eosinophilic leukemia, chronic neutrophilic leukemia, myelodysplastic/myeloproliferative disease, unclassifiable, adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(15;17)(q22;q12), childhood myelodysplastic syndromes

DISEASE CHARACTERISTICS: Diagnosis of 1 of the following: Myelodysplastic syndromes (including those that have evolved to acute myeloid leukemia) Myeloproliferative disorders No chronic myelogenous leukemia Other diseases eligible for conditioning with targeted busulfan, cyclophosphamide, and anti-thymocyte globulin that are not candidates for other studies Available related or unrelated donor compatible for HLA-A, -B, -C, DRB1, and DQB1 A single allele mismatch at HLA-A, -B, -C, or DRB1 is allowed PATIENT CHARACTERISTICS: Age 65 and under Performance status Not specified Life expectancy No severe limitation due to other diseases Hematopoietic Not specified Hepatic AST no greater than 2 times normal No hepatic disease Renal Creatinine no greater than 2 times upper limit of normal OR Creatinine clearance at least 50% for age, gender, and weight Cardiovascular No cardiac insufficiency requiring treatment No symptomatic coronary artery disease Pulmonary No severe or mild hypoxemia pO_2 at least 70 mm Hg and DLCO at least 70% of predicted OR pO_2 at least 80 mm Hg and DLCO at least 60% of predicted Other Not pregnant or nursing Fertile patients must use effective contraception HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy No growth factors given posttransplantation concurrently with methotrexate immunosuppression Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified