Cyclophosphamide Plus T-Cell Transplantation for Patients With Hematologic Malignancies

Cyclophosphamide Plus Transplantation of Partially HLA-mismatched (Haploidentical), CD8+ T Cell-depleted Peripheral Blood Cells for Patients With Myelodysplastic Syndrome, Acute Myeloid Leukemia, Lymphoma, or Myeloproliferative Disorders

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of abnormal blood cells, either by killing the cells or by stopping them from dividing. Giving cyclophosphamide together with donor lymphocytes that have been treated in the laboratory may be an effective treatment for myelodysplastic syndromes or myeloproliferative disorders.

PURPOSE: This clinical trial is studying the best dose of donor lymphocytes when given together with cyclophosphamide in treating patients with myelodysplastic syndromes or myeloproliferative disorders.

OBJECTIVES:

• Determine the maximum tolerated dose of allogeneic CD8-positive T-cell-depleted, haploidentical donor lymphocytes when given after cyclophosphamide in patients with myelodysplastic syndromes or myeloproliferative disorders.

OUTLINE: Patients receive cyclophosphamide on days 1 and 2. Patients then undergo infusion of allogeneic T-cell depleted donor lymphocytes on day 3.

Cohorts of patients receive escalating doses of CD8-positive T-cell-depleted haploidentical donor lymphocytes until the maximum tolerated dose is determined.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

  • Myelodysplastic syndromes (MDS)

    • International Prognostic Scoring System (IPSS) score ≥ intermediate-2

  • Chronic myelomonocytic leukemia

  • Acute myeloid leukemia arising from MDS

• Must have failed or are ineligible for or intolerant to treatment with azacitidine

  • Patients with normal marrow cytogenetics or an isolated 5q- abnormality must have failed or are ineligible for or intolerant to treatment with lenalidomide
  • Patients who are HLA-DR15-positive must have failed or are ineligible for pharmacologic immunosuppression (e.g., anti-thymocyte globulin, cyclosporine, steroids)

• No presence of cytotoxic antibodies against donor lymphocytes

• No HLA-identical donor available OR ineligible for HLA-identical allogeneic bone marrow transplantation

• HLA partially mismatched (haploidentical) related donor available

  • First-degree related donor, including half-siblings or first cousins
  • Inherited recombinant haplotype from parents allowed if donor shares ≥ 1 HLA antigen at each of the HLA-A, -B, and DR loci

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 OR Karnofsky PS 80-100%
• Bilirubin < 3.0 mg/dL
• AST and ALT ≤ 4 times upper limit of normal
• Creatinine < 3.0 mg/dL
• LVEF > 35%

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• No prior transfusions from donor
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy
• No other concurrent investigational drugs