Donor Bone Marrow Transplant With or Without G-CSF in Treating Young Patients With Hematologic Cancer or Other Diseases

PRIMARY OBJECTIVE:

I. Compare improvement in event-free survival of patients with hematologic cancer or other
diseases undergoing filgrastim (G-CSF)-stimulated bone marrow transplantation (BMT) vs
conventional BMT.

SECONDARY OBJECTIVES:

I. Compare the incidence and time to engraftment in patients treated with these regimens.

II. Compare rates of acute and chronic graft-vs-host disease (GVHD) in patients treated with
these regimens.

III. Correlate incidence of acute and chronic GVHD with absolute T-cell numbers, Th1 vs Th2
profile of T cells, dendritic cell populations, and T-regulatory cell content.

IV. Assess the impact of G-CSF-stimulated BMT as a stem cell source on hospital stay and
treatment-related mortality at day 100 in patients treated with this regimen.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to risk
(high vs intermediate vs standard).

CONDITIONING REGIMEN: Co-enrolled on COG-ASCT0431 or COG-AAML0531; Patients receive a
conditioning regimen as defined on that treatment study.

ACUTE LYMPHOBLASTIC LEUKEMIA (ALL): Patients undergo total-body irradiation (TBI) twice
daily on days -8 to -6. Patients receive thiotepa IV on days -5 and -4 and high-dose
cyclophosphamide IV over 1 hour on days -3 and -2. Some patients with CNS leukemia or very
high-risk ALL in first complete remission receive cranial radiotherapy.

ACUTE MYELOID LEUKEMIA, JUVENILE MYELOMONOCYTIC, CHRONIC MYELOGENOUS LEUKEMIA, OR
MYELODYSPLASTIC SYNDROMES: (myeloid malignancies) Patients receive busulfan IV over 2 hours
every 6 hours on days -9 to -6 and high-dose cyclophosphamide IV over 1 hour on days -5 to
-2.

GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Co-enrolled on COG-ASCT0431 or COG-AAML0531:
Patients undergo GVHD prophylaxis as defined on that treatment study.

ALL: Patients receive tacrolimus IV or orally beginning on day -2 and continuing until day
42, followed by a taper until day 98. Patients also receive methotrexate IV on days 1, 3,
and 6.

MYELOID MALIGNANCIES: Patients receive cyclosporine IV continuously or orally beginning on
day -1 and continuing until day 42 or day 50, followed by a taper for 8-16 weeks. Patients
also receive methotrexate IV on days 1, 3, 6, and 11.

ALLOGENEIC BONE MARROW TRANSPLANTATION (BMT): Patients are randomized to 1 of 2
transplantation arms.

ARM I: Patients undergo filgrastim (G-CSF) -stimulated allogeneic BMT on day 0.

ARM II: Patients undergo conventional allogeneic BMT on day 0.

After completion of study treatment, patients are followed at 1 year and then annually for
5-10 years.

Inclusion Criteria:

- Diagnosis of hematologic cancer or other disease, including any of the following:

- Chronic myelogenous leukemia in first or second chronic phase

- Acute lymphoblastic leukemia (ALL), meeting any of the following criteria:

- Relapsed ALL enrolled on a Children's Oncology Group (COG) relapse clinical
trial OR received ≥ 1 round of reinduction therapy (4-6 weeks) and 1 round
of intensive consolidation chemotherapy (3-6 weeks)

- ALL in second complete remission (CR)* after a bone marrow, extramedullary,
or combined bone marrow and extramedullary relapse

- Very high-risk ALL in first CR, defined as any of the following:

- Philadelphia chromosome-positive ALL

- Hypodiploidy (< 44 chromosomes)

- Mixed lineage leukemia rearrangement

- Induction failure

- Acute myeloid leukemia in first or second CR

- Induction therapy must be completed

- Juvenile myelomonocytic leukemia

- Myelodysplastic syndromes

- No clinically evident CNS or extramedullary disease

- No blasts seen on cerebrospinal fluid cytospin

- Post-relapse reinduction therapy must be completed

- Not planning to receive reduced-intensity conditioning regimen

- Not planning to receive a graft that has undergone T-cell depletion

- No Down syndrome

- Matched sibling donor must be available and must be enrolled on ASCT0631D companion
study

- Karnofsky performance status (PS) 60-100% (patients > 16 years of age) OR Lansky PS
60-100% (patients ≤ 16 years of age)

- AST or ALT < 5 times upper limit of normal for age

- Bilirubin < 2.5 mg/dL (unless due to Gilbert's syndrome)

- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum
creatinine base on age and/or gender as follows:

- 0.4 mg/dL (1 month to < 6 months of age)

- 0.5 mg/dL (6 months to < 1 year of age)

- 0.6 mg/dL (1 to 2 years of age)

- 0.8 mg/dL (2 to < 6 years of age)

- 1.0 mg/dL (6 to < 10 years of age)

- 1.2 mg/dL (10 to < 13 years of age)

- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

- 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)

- Shortening fraction ≥ 27% by echocardiogram OR LVEF ≥ 50% by radionuclide angiogram

- FEV_1, FVC, and DLCO ≥ 60% OR meets the following criteria (for patients unable to
cooperate for pulmonary function tests):

- No evidence of dyspnea at rest

- No exercise intolerance

- No requirement for supplemental oxygen therapy

- Not pregnant or nursing

- No known HIV

- No known uncontrolled fungal, bacterial, or viral infections

- Patients acquiring fungal disease during induction therapy may proceed if they
have a significant response to antifungal therapy with no or minimal evidence of
disease remaining by CT scan

- No prior allogeneic or autologous stem cell transplantation