Donor Stem Cell Transplant in Treating Patients With Relapsed Hematologic Cancer

OBJECTIVES:

- Determine the feasibility of non-myeloablative allogeneic hematopoietic stem cell
transplantation by demonstrating that the risk of treatment-related mortality during
the first 6 months is an acceptable rate of less than 40% in patients with relapsed
hematologic malignancies after prior high-dose chemotherapy and autologous stem cell
transplantation.

- Determine the response rates (disease-specific partial and complete response) in
patients treated with this regimen.

- Determine the 6-month and 12-month probabilities of response in patients treated with
this regimen.

- Determine the distribution of time-to-progression in patients responding to this
regimen.

- Determine the percent donor chimerism in patients treated with this regimen.

- Determine the risk of acute and chronic graft-vs-host disease in patients treated with
this regimen.

- Determine the toxic effects of this regimen in these patients.

- Determine the disease-free and overall survival of patients treated with this regimen.

OUTLINE: This is an open-label study.

- Preparative Regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3
and busulfan IV over 2 hours every 6 hours (for a total of 8 doses) on days -4 and -3.

- Graft vs Host Disease (GVHD) Prophylaxis: Patients who have an HLA-identical donor
receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily
on days -1 to 90 followed by a taper^* until day 150 and methotrexate IV on days 1, 3,
and 6. Patients with a matched related or matched unrelated donor receive oral (or IV
if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 180
followed by a taper^* as tolerated; methotrexate IV on days 1, 3, 6, and 11; oral
mycophenolate mofetil twice daily on days -2 to 60 followed by a taper; and rabbit
anti-thymocyte globulin IV over 4-6 hours on days -4 to -1 (for a total of 4 doses).

NOTE: *Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is less than
50% at day 60 or patient has progressive disease

- Allogeneic Stem Cell Transplantation: Patients undergo allogeneic bone marrow or
peripheral blood stem cell transplantation on days 0 and 1. Patients then receive
filgrastim (G-CSF) subcutaneously daily beginning on day 7 and continuing until blood
counts recover.

- Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an
HLA-identical donor), patients with stable or progressive disease and no active GVHD
may receive up to 3 DLIs every 8 weeks.

Patients are followed within 2-3 months, every 3 months for 2 years, and then every 6 months
for 3 years.

DISEASE CHARACTERISTICS:

- Histologically confirmed hematologic malignancy, including one of the following:

- Chronic lymphocytic leukemia (CLL)

- Absolute lymphocytosis greater than 5,000/mm^3

- Lymphocytes must appear morphologically mature with less than 55%
prolymphocytes

- Lymphocyte phenotype with expression of CD19 and CD5

- Prolymphocytic leukemia (PLL)

- Morphologically confirmed

- Absolute lymphocytosis greater than 5,000/mm^3

- More than 55% prolymphocytes

- Non-Hodgkin's lymphoma or Hodgkin's lymphoma

- Any WHO histologic subtype allowed except mantle cell lymphoma

- Core biopsies allowed if they contain adequate tissue for primary diagnosis
and immunophenotyping

- No bone marrow biopsy as the sole diagnostic means for follicular lymphoma

- Multiple myeloma

- Active disease requiring treatment

- Durie-Salmon stage I, II, or III

- Acute myeloid leukemia

- Documented control (i.e., less than 10% bone marrow blasts and no
circulating blasts)

- Myelodysplastic syndromes

- Documented disease by WHO criteria

- Must have evidence of relapse/progression at least 6 months after prior high-dose
chemotherapy with autologous hematopoietic stem cell support

- Absence of CD23 expression for CLL or PLL allowed provided there is no morphologic
evidence of mantle cell lymphoma

- Availability of any of the following donor types:

- HLA-identical sibling (6/6)

- 9/10 matched related donor by high-resolution molecular typing at HLA A, B, C,
DRB1, and DQB1 loci

- Only a single mismatch at one class I or II allele allowed

- 10/10 matched unrelated donor by high-resolution molecular typing at HLA A, B,
C, DRB1, and DQB1 loci

- No syngeneic donors

PATIENT CHARACTERISTICS:

Age

- Under 70

Performance status

- Not specified

Life expectancy

- Not specified

Hematopoietic

- See Disease Characteristics

Hepatic

- Bilirubin no greater than 3 times upper limit of normal (ULN)

- AST no greater than 3 times ULN

Renal

- Creatinine clearance at least 40 mL/min

Cardiovascular

- LVEF at least 30% by MUGA

Pulmonary

- DLCO greater than 40%

- No symptomatic pulmonary disease

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- No uncontrolled diabetes mellitus

- No active serious infection

- No known hypersensitivity to E. coli-derived products

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

Chemotherapy

- See Disease Characteristics

- More than 4 weeks since prior chemotherapy

Endocrine therapy

- Not specified

Radiotherapy

- More than 4 weeks since prior radiotherapy

Surgery

- More than 4 weeks since prior surgery