OBJECTIVES:

• Determine the feasibility and efficacy of a reduced-intensity conditioning regimen comprising alemtuzumab, fludarabine, melphalan, and thiotepa followed by allogeneic peripheral blood stem cell transplantation (PBSCT) in patients with hematologic malignancies.
• Determine the toxicity of this regimen in these patients.
• Determine the safety of LMB-2 immunotoxin-treated, selectively-depleted donor T cells, administered after allogeneic PBSCT, in these patients.

OUTLINE: This is a dose-escalation study of LMB-2 immunotoxin-treated, selectively-depleted donor T cells.

• T cell preparation: Patients and donors undergo apheresis to obtain peripheral blood mononuclear cells (PBMCs), which are expanded in culture. Patients' PBMCs are irradiated and mixed with donor PBMCs. LMB-2 immunotoxin is added to the PBMCs in order to selectively deplete T cells from the donor PBMCs.
• Conditioning: Patients receive alemtuzumab IV over 2 hours on days -9 to -5, fludarabine IV over 30 minutes on days -8 to -5, melphalan IV over 15-20 minutes on day -4, and thiotepa IV on days -3 to -2.
• Immunosuppression: Patients receive tacrolimus IV continuously on days -10 to 1.
• Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients undergo allogeneic PBSC transplantation on day 0.
• LMB-2 immunotoxin-treated, selectively-depleted donor T cells: Patients receive LMB-2 immunotoxin-treated, selectively-depleted donor T cells IV over 30-60 minutes on approximately day 28.

Cohorts of 3-6 patients receive escalating dose of LMB-2 immunotoxin-treated, selectively-depleted donor T cells until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting-toxicity.

After completion of study treatment, patients are followed weekly for 100 days post-transplantation and then periodically for survival.

PROJECTED ACCRUAL: A total of 15-20 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following hematologic malignancies:

  • Chronic myelogenous leukemia

    • Accelerated phase or blast phase

  • Acute myeloid leukemia, meeting any of the following criteria:

    • In second or subsequent remission
    • In primary induction failure
    • In partial remission
    • In resistant relapse

  • Chronic lymphocytic leukemia

    • In Richter's transformation

  • High-grade non-Hodgkin's lymphoma

    • Refractory to standard treatment

  • Myeloproliferative disorders

    • Undergoing transformation to terminal stages

  • Myelodysplastic syndromes (MDS), including any of the following:

    • Refractory anemia with excess blasts
    • Transformation to acute leukemia
    • MDS secondary to chemotherapy

• Partially-matched related family donor available

  • One HLA haplotype match
• No HLA-matched (10/10 or 9/10) sibling donor or unrelated donor available NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

• 18 to 55

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• SGOT and SGPT < 3 times upper limit of normal (ULN)
• No active or persistent viral hepatitis

Renal

• Creatinine < 2.0 mg/dL* OR
• Creatinine clearance > 60 mL/min* NOTE: *Unless due to malignancy

Cardiovascular

• LVEF ≥ 45%

Pulmonary

• DLCO ≥ 60% of predicted* (corrected for hemoglobin) NOTE: *Unless patient is given clearance by a pulmonary consultation

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for up to 2 years after completion of study treatment
• HIV negative
• Human T cell lymphotrophic virus type 1 negative
• No serious co-morbid medical condition
• No other medical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified