• Durable hematopoietic reconstitution [ Designated as safety issue: No ]
  
• Incidence and characteristics of peritransplantation morbidity and mortality [ Designated as safety issue: No ]
  
• Incidence and severity of acute and chronic graft-versus-host disease [ Designated as safety issue: No ]
  
• Overall and disease-free survival at 1, 3, 6, 12, and 24 months after transplantation [ Designated as safety issue: No ]
  

• Quality of bone marrow and peripheral blood chimerism at 1, 3, 6, 12, and 24 months after transplantation [ Designated as safety issue: No ]
  
• Kinetics of immune reconstitution [ Designated as safety issue: No ]
  

OBJECTIVES:

• Evaluate the proportion of patients with lymphohematopoietic malignancies who achieve durable hematopoietic reconstitution after receiving a nonmyeloablative regimen comprising melphalan, fludarabine, and alemtuzumab followed by allogeneic hematopoietic stem cell transplantation.
• Determine the incidence and characteristics of peritransplantation morbidity and mortality (e.g., hepatic veno-occlusive disease or infections) in patients treated with this regimen.
• Determine the incidence and severity of acute and chronic graft-versus-host disease in these patients treated with this regimen.
• Determine the overall and disease-free survival at 1, 3, 6, 12, and 24 months after transplantation in these patients.
• Determine the quality of bone marrow and peripheral blood chimerism at 1, 3, 6, 12, and 24 months after transplantation in these patients.
• Assess the kinetics of immune reconstitution in patients treated with this regimen.

OUTLINE: Patients are stratified according to donor type (HLA-matched related vs HLA-matched unrelated, single HLA-allele disparate related, or unmatched) (HLA-mismatched related or matched unrelated donor stratum closed to accrual as of 1/11/06).

Patients receive a nonmyeloablative regimen comprising alemtuzumab IV over 8 hours on days -8 to -5, fludarabine IV over 30 minutes on days -8 to -4, and melphalan IV over 30 minutes on days -3 and -2. Allogeneic peripheral blood stem cells or bone marrow is infused on day 0.

Patients receive graft-versus host disease prophylaxis comprising cyclosporine IV every 12 hours beginning on day -1 and continuing orally as tolerated until day 100.

Patients are followed every 6 weeks for 6 months, every 3 months for 6 months, every 3-6 months for 1 year, and then annually thereafter or as clinically indicated.

PROJECTED ACCRUAL: A maximum of 50 patients (25 HLA-matched related and 25 HLA-mismatched related or matched unrelated) will be accrued for this study within 2 years (HLA-mismatched related or matched unrelated donor stratum closed to accrual as of 1/11/06).

DISEASE CHARACTERISTICS:

• Diagnosis of one of the following:

  • Relapsed or primary refractory non-Hodgkin's lymphoma (NHL)

    • Aggressive NHL histologies allowed if the following criteria are met:

      • Chemosensitive/radiosensitive, nonprogressive, or stable on therapy
      • Ineligible for autologous hematopoietic stem cell transplantation because of disease in bone marrow
  • Chemosensitive relapsed or refractory acute lymphoblastic leukemia or chronic lymphocytic leukemia
  • Relapsed or primary refractory Hodgkin's lymphoma
  • Stage II or III multiple myeloma
  • Advanced or refractory Waldenstrom's macroglobulinemia

• Ineligible for protocols involving myeloablative conditioning regimens by virtue of any of the following conditions:

  • Advanced age
  • Intensity of prior radiotherapy and/or chemotherapy
  • History of prior toxicity associated with chemotherapy/radiotherapy
  • Existing organ damage
• Diagnosis of chronic myeloid leukemia, high-risk acute myelogenous leukemia, or myelodysplastic syndromes allowed if no alternative, active, higher priority allogeneic transplantation protocol exists
• Availability of an HLA-matched or a single HLA allele disparate related or unrelated donor (HLA-mismatched related or matched unrelated donor stratum closed to accrual as of 1/11/06)
• No uncontrolled CNS disease

PATIENT CHARACTERISTICS:

Age:

• 70 and under

Performance status:

• Karnofsky 40-100%

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 2.5 mg/dL
• AST and ALT no greater than 3 times normal unless due to liver involvement with disease

Renal:

• Creatinine no greater than 2.0 mg/dL OR
• Creatinine clearance at least 30 mL/min

Cardiovascular:

• Resting LVEF at least 30% by echocardiogram or MUGA scan

Pulmonary:

• DLCO at least 40% of predicted
• No requirement for supplementary oxygen

Other:

• HIV negative
• HTLV negative
• No active or uncontrolled bacterial, viral, or fungal infection that would preclude myelosuppressive chemotherapy
• Not pregnant or nursing
• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy:

• See Disease Characteristics

Surgery:

• Not specified

Other:

• Concurrent cardiac medication for congestive heart failure allowed