• 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 ]

• Durable hematopoietic reconstitution
• Incidence and characteristics of peritransplantation morbidity and mortality
• Incidence and severity of acute and chronic graft-versus-host disease
• Overall and disease-free survival at 1, 3, 6, 12, and 24 months after transplantation

• 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 ]

• Quality of bone marrow and peripheral blood chimerism at 1, 3, 6, 12, and 24 months after transplantation
• Kinetics of immune reconstitution

RATIONALE: Giving low doses of chemotherapy, such as melphalan and fludarabine, and a monoclonal antibody, such as alemtuzumab, before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well fludarabine, melphalan, alemtuzumab, and peripheral stem cell transplant work in treating patients with hematologic cancer.

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).

• Leukemia
• Lymphoma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic/Myeloproliferative Diseases

• Biological: alemtuzumab
• Drug: cyclosporine
• Drug: fludarabine phosphate
• Drug: melphalan
• Procedure: allogeneic bone marrow transplantation
• Procedure: peripheral blood stem cell transplantation

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