Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Disease

OBJECTIVES:

- Determine the overall survival rate at day 200 in patients with hematologic cancers or
other diseases who undergo allogeneic peripheral blood stem cell transplantation using
the CliniMACS® CD34 Reagent System for T-cell depletion followed by delayed T-cell
add-back.

- Determine the safety of this regimen, in terms of the nonrelapse mortality rate at day
200, in these patients.

OUTLINE:

- Myeloablative preparative regimen: Patients receive fludarabine phosphate IV over 30
minutes on days -8 to -4 and cyclophosphamide IV over 1 hour on days -3 and -2.
Patients also undergo high-dose* total body irradiation (TBI) twice daily on days -7 to
-4.

NOTE: *Patients over 55 years of age receive reduced-dose TBI.

- Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients receive
T-cell-depleted (via the CliniMACS® CD34 Reagent System), filgrastim (G-CSF)-mobilized,
donor PBSC IV over 4 hours on day 0.

- Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine (or
tacrolimus) IV or orally twice daily on days -6 to 21, and then again beginning on day
89 and continuing up to day 150, followed by a slow taper to day 180, in the absence of
GVHD.

- Donor lymphocyte infusion (DLI): Patients receive delayed T-cell add-backs of donor
lymphocytes IV over 1 hour on day 90. If relapse occurs, patients may receive DLI
before day 90 or as a repeat infusion.

After completion of study therapy, patients are followed periodically for 3 years.

DISEASE CHARACTERISTICS:

- Diagnosis of 1 of the following:

- Chronic myelogenous leukemia (CML), meeting 1 of the following criteria:

- Under 21 years of age and in chronic phase

- Ten to 75 years of age with CML in chronic phase, meeting 1 of the
following criteria:

- Failed or intolerant to prior treatment with imatinib mesylate

- No prior therapeutic doses of imatinib mesylate within 12 months after
disease diagnosis

- Ten to 75 years of age with CML in accelerated phase or blast
transformation

- Acute lymphoblastic leukemia, meeting 1 of the following criteria:

- In first remission with any of the following high-risk features:

- WBC > 100,000/mm³ at diagnosis

- Karyotypes t9; 22, t4, t19, t11, or biphenotypic leukemia

- In second or subsequent remission

- Primary induction failure

- Partially responding or untreated relapsed disease

- Acute myeloid leukemia (AML), meeting 1 of the following criteria:

- In first remission

- No AML with good-risk karyotypes (e.g., M3 [t15; 17], M4Eo [inv 16], t
[8; 21])

- In second or subsequent remission

- Primary induction failure

- Resistant relapsed disease

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

- Refractory anemia with transfusion dependence

- Refractory anemia with excess blasts

- MDS in transformation to acute leukemia

- Chronic myelomonocytic leukemia

- Atypical MDS/myeloproliferative disorders

- Myeloproliferative disorders, including any of the following subtypes:

- Atypical (Philadelphia chromosome negative) chronic myelogenous or
neutrophilic leukemias

- Progressing myelofibrosis

- Polycythemia vera

- Essential thrombocythemia in transformation to acute leukemia

- Essential thrombocythemia with progressive transfusion requirements or
pancytopenia

- Chronic lymphocytic leukemia

- Refractory to fludarabine phosphate treatment AND meets 1 of the following
criteria:

- Bulky progressive disease

- Thrombocytopenia (i.e., platelet count ≤ 100,000/mm^3) not due to
recent chemotherapy

- Anemia (i.e., hemoglobin ≤ 10 g/dL) not due to recent chemotherapy

- Non-Hodgkin's lymphoma, including mantle cell lymphoma, that has relapsed or is
refractory to standard-of-care treatments

- Multiple myeloma or Waldenstrom's macroglobulinemia that is unresponsive to or
relapsed after standard-of-care treatments

- HLA-identical (6/6) related donor available

PATIENT CHARACTERISTICS:

- Life expectancy ≥ 3 months

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No major anticipated illness or organ failure incompatible with survival from
transplantation

- No severe psychiatric illness or mental deficiency that would preclude study
compliance

- HIV negative

- DLCO ≥ 65% of predicted

- LVEF ≥ 40%

- AST ≤ 20 times upper limit of normal (ULN)

- Bilirubin ≤ 10 times ULN

- Creatinine ≤ 6 times ULN

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior allogeneic stem cell transplantation