T-cell Depleted Bone Marrow and G-CSF Stimulated Peripheral Stem Cell Transplantation From Related Donors in Treating Patients With Leukemia, Lymphoblastic Lymphoma, Myelodysplastic Syndrome, or Aplastic Anemia

OBJECTIVES:

- Determine the potential of T-cell-depleted bone marrow and peripheral blood stem cells
(PBSC) from HLA-haplotype, partially matched related donors to induce extended
disease-free survival in patients with leukemia, lymphoblastic lymphoma,
myelodysplastic syndrome, or severe aplastic anemia who would otherwise be ineligible
for transplantation because of the lack of an HLA-identical related or unrelated donor.

- Determine the impact of filgrastim (G-CSF)-stimulated, CD34+, E-rosette and
T-cell-depleted PBSC derived from an HLA-haplotype, partially matched donor on the
incidence and quality of engraftment, kinetics, and quality of hematopoietic and
immunologic reconstitution, and incidence and severity of graft-versus-host disease
(GVHD) in these patients.

- Correlate the doses of PBSC and clonable T-cells with the incidence of engraftment,
extent of chimerism, incidence and severity of acute and chronic GVHD, characteristics
of hematopoietic and immunologic reconstitution, and overall and disease-free survival
rates at 2-4 years after transplantation in these patients.

OUTLINE: Patients are stratified by number of HLA-incompatible alleles (1 vs 2 or 3).

- Harvest: Beginning 6-10 days before transplantation, allogeneic bone marrow is
harvested and treated in vitro. Beginning 5-6 days before transplantation, filgrastim
(G-CSF)-stimulated, allogeneic peripheral blood stem cells (PBSC) are harvested,
selected for CD34+ cells, and treated in vitro. If feasible, autologous bone marrow is
harvested in the event of allogeneic graft failure.

- Myeloablation: Patients undergo total body irradiation 3 times a day on days -9 to -6,
thiotepa IV over 4 hours on days -5 and -4, and cyclophosphamide IV on days -3 and -2.

- Transplantation: CD34+, E-rosette and T-cell-depleted PBSC are infused over 15 minutes
and then T-cell-depleted bone marrow is infused over 1-5 minutes on day 0. Patients
receive G-CSF IV over 30 minutes beginning on day 1 and continuing until blood counts
recover and then tapering. Patients receive anti-thymocyte globulin IV over 4-6 hours
on days 8, 10, 12, and 14 and oral methylprednisolone on days 8-14 followed by tapered
doses on days 15-17.

- CNS prophylaxis: Beginning at least 2 months after transplantation, patients with acute
lymphocytic leukemia (ALL) and no history of CNS leukemia receive cytarabine
intrathecally (IT) monthly for 6 months and patients with ALL and a history of CNS
leukemia receive cytarabine IT monthly for 12 months.

Patients with graft failure are offered autologous bone marrow transplantation (BMT) or
second allogeneic BMT.

Patients are followed at 1, 3, 6, and 12 months and then annually for 3 years.

DISEASE CHARACTERISTICS:

- One of the following diagnoses:

- Acute myelogenous leukemia (AML) meeting 1 of the following conditions:

- Failed to achieve first remission after an intensive induction regimen
containing an anthracycline and cytarabine

- In second remission and not enrolled in a protocol for autologous bone
marrow transplantation

- Failed to achieve or sustain second remission

- In first remission but at high risk of relapse because of 1 of the
following factors:

- High-risk cytogenetic features (monosomy 7,5q-, trisomy 8, or t(9;22))

- AML secondary to treatment of a prior malignancy and without good-risk
cytogenetic features of t(8;21), t(15;17), or inv 16

- AML secondary to myelodysplastic disease

- Acute lymphocytic leukemia (ALL) meeting 1 of the following conditions:

- In second remission with initial relapse occurring within 2 years of
diagnosis

- In first complete remission with high-risk cytogenetics (t(9;22) or
t(4;11))

- In third or subsequent remission

- Failed to achieve or sustain a second remission

- Chronic myelogenous leukemia (CML) in first or second chronic phase or
accelerated phase

- Stage IV lymphoblastic lymphoma not in first remission or that failed to achieve
a remission within the first 4 weeks of induction therapy

- Juvenile CML

- Myelodysplastic syndrome

- Severe aplastic anemia unresponsive to anti-thymocyte globulin or cyclosporine

- No CNS or skin involvement with leukemia

- No requirement for mediastinal irradiation

- No healthy, HLA-identical related donor of at least 1 year of age or matched
unrelated donor available within 4-6 months

- Availability of a healthy, 1-3 HLA-A, -B, and -DR mismatched related donor

- Willing and able to undergo general anesthesia for marrow donation and a 5-day
course of filgrastim (G-CSF) with 2 daily leukaphereses

PATIENT CHARACTERISTICS:

Age:

- Under 50 (50 and over allowed on a case-by-case basis)

Performance status:

- Age 16 and over:

- Karnofsky 70-100%

- Under age 16:

- Lansky 50-100%

Hematopoietic:

- Not specified

Hepatic:

- Bilirubin less than 2.0 mg/dL (in the absence of liver involvement)

- AST less than twice normal (in the absence of liver involvement)

Renal:

- Creatinine normal OR

- Creatinine clearance greater than 60 mL/min

Cardiovascular:

- Asymptomatic or LVEF greater than 50% at rest, with improvement during exercise

Pulmonary:

- Asymptomatic or DLCO greater than 50% predicted (corrected for hemoglobin)

Other:

- No known hypersensitivity to mouse protein or chicken egg products

- No active viral, bacterial, or fungal infection

- HIV-1, HIV-2, HTLV-1, and HTLV-2 negative

- No other concurrent medical condition that would preclude transplantation

- Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

Chemotherapy

- See Disease Characteristics

Endocrine therapy

- Not specified

Radiotherapy

- See Disease Characteristics

Surgery

- See Disease Characteristics