Bone Marrow Transplantation in Treating Patients With Leukemia

OBJECTIVES: I. Compare unrelated donor bone marrow transplantation using T-cell-depleted
marrow versus unmodified marrow in adults and children with leukemia. II. Evaluate 2-year
leukemia-free survival, primary and secondary graft failure, graft-versus-host disease,
infection, and relapse in these patients. III. Assess the quality of life associated with
T-cell-depleted versus unmodified, unrelated donor transplantation.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by center. Patients
receive myeloablative therapy according to diagnosis: those with acute lymphocytic leukemia
and lymphoblastic lymphoma are treated with total body irradiation (TBI), with a testicular
and chest wall boost as appropriate, followed by cyclophosphamide (CTX); patients with
undifferentiated or biphenotypic leukemia or with acute or chronic myelocytic leukemia are
treated with CTX followed by TBI. Patients are then randomly assigned to receive
non-T-cell-depleted, unrelated marrow versus T-cell-depleted, unrelated marrow. The modified
marrow is depleted of T-lymphocytes by counterflow elutriation and positively selected for
CD34 cells. Graft-versus-host disease (GVHD) prophylaxis with cyclosporine and methotrexate
is given to the unmodified marrow group. Patients who receive modified marrow are given
antithymocyte globulin (or methylprednisolone) for graft rejection prophylaxis before
transplantation and cyclosporine and methylprednisolone for GVHD prophylaxis after
transplantation.

DISEASE CHARACTERISTICS: Acute myelocytic leukemia with or without history of
myelodysplastic syndrome Not in first complete remission (i.e., greater than 5% blasts in
marrow) with t(8;21), t(15;17), or 16q abnormality unless failure on first-line induction
therapy Acute lymphocytic leukemia (ALL) in one of the following categories: In second or
third complete remission (CR) High-risk ALL in first CR, with high risk defined as:
Hypodiploidy OR pseudodiploidy with t(9;22), t(4;11), or t(8;14) Failure to achieve CR
after 4 weeks of induction therapy Elevated WBC at presentation, i.e.: Greater than 100,000
in patients aged 6 to 12 months Greater than 200,000 in patients aged 1 to 20 years Greater
than 20,000 in patients aged 21 to 44 years Chronic myelogenous leukemia not in blast
crisis (i.e., no greater than 30% promyelocytes plus blasts in bone marrow) Stage IV
lymphoblastic lymphoma Undifferentiated or biphenotypic leukemia Unrelated donor available
Patients aged 35 and younger: HLA-A, and -B serologic identity and HLA-DRB1 identity by
high-resolution DNA typing OR Single HLA-A or -B serologic mismatch with DRB1 identity by
high-resolution DNA typing OR HLA-A and -B serologic identity with single DRB1 mismatch by
high- or low- resolution DNA typing Patients aged 36 to 44: HLA-A and -B serologic identity
and HLA-DRB1 identity by high-resolution DNA typing The following exclude: Relapse 12
months after discontinuing therapy in patients aged 1 to 10 years who are in second
remission Active central nervous system or leukemic skin involvement Requirement for
additional mediastinal irradiation

PATIENT CHARACTERISTICS: Age: Under 46 Performance status: Karnofsky 70-100% Lansky 50-100%
Hematopoietic: See Disease Characteristics Hepatic: Bilirubin less than 2.5 mg/dL AST less
than 3 times normal Renal: Creatinine normal OR Creatinine clearance greater than 60 mL/min
Cardiovascular: Asymptomatic OR Resting LVEF greater than 40% and improves with exercise
Pulmonary: Asymptomatic OR DLCO greater than 45% of predicted (corrected for hemoglobin)
Other: HIV negative No uncontrolled viral, bacterial, or fungal infection Not pregnant or
nursing

PRIOR CONCURRENT THERAPY: No prior bone marrow transplantation No prior radiotherapy that
precludes total body irradiation