Chemotherapy Followed by Allogeneic Stem Cell Transplantation in Treating Children With Hematologic Cancer

OBJECTIVES:

Primary

- Determine the efficacy and safety of non-myeloablative chemotherapy in facilitating
donor engraftment after allogeneic stem cell transplantation with G-CSF mobilized
peripheral blood stem cells in patients with pediatric hematopoietic malignancies.
(Cohort 1) (closed to accrual as of 09/29/2005)

- Determine the efficacy and safety of non-myeloablative chemotherapy in facilitating
donor engraftment after allogeneic stem cell transplantation with G-CSF primed bone
marrow derived stem cells in these patients. (Cohort 2)

Secondary

- Determine the toxicity of this regimen in these patients. (Cohorts 1 and 2)

- Evaluate the ability of this non-myeloablative chemotherapy regimen to reduce the
peripheral blood T-cell count in these patients. (Cohorts 1 and 2)

- Correlate IL-7 levels with immune suppression and recovery in patients treated with
these regimens. (Cohorts 1 and 2)

- Correlate cytokine profiles with treatment and graft-versus-host disease (GVHD) in
patients treated with this regimen. (Cohort 1) (closed to accrual as of 09/29/2005)

- Determine response rates and disease-free survival rates in patients treated with these
regimens. (Cohorts 1 and 2)

- Determine the incidence and severity of GVHD in patients achieving donor engraftment
after treatment with these regimens. (Cohorts 1 and 2)

- Determine response rates, disease-free survival rates, and incidence and severity of
GVHD after withdrawal of immunosuppression and donor lymphocyte infusions for patients
who develop progressive disease after day 28 post-transplantation. (Cohorts 1 and 2)

OUTLINE:

- Harvest: Donors undergo mobilization of peripheral blood stem cells (cohort 1) (closed
to accrual as of 09/29/05) or bone marrow derived stem cells by bone marrow harvest
(cohort 2).

- Induction: Patients with lymphoma receive fludarabine IV over 30 minutes on days 1-3
and etoposide, doxorubicin, and vincristine IV over 24 hours daily on days 1-4.
Patients also receive cyclophosphamide IV over 30 minutes on day 5, oral prednisone 2-4
times daily on days 1-5, and filgrastim (G-CSF) subcutaneously (SC) once daily
beginning on day 6 and continuing until blood counts recover.

Patients with leukemia or myelodysplastic syndromes receive fludarabine IV over 30 minutes
and cytarabine IV over 4 hours on days 1-5. Patients also receive G-CSF SC once daily
beginning on day 0 and continuing until blood counts recover.

For all patients, treatment repeats every 21 days for up to 3 courses until the target
absolute CD4 count is achieved.

- Preparative regimen: On day 22 after the final course of induction chemotherapy,
patients receive fludarabine IV over 30 minutes and cyclophosphamide IV over 2 hours
once daily for 4 days (transplantation days -6 to -3).

- Transplantation: Patients are assigned to 1 of 2 cohorts based on time of study entry.

- Cohort 1 (closed to accrual as of 09/29/2005): Patients receive G-CSF mobilized
peripheral blood stem cells on day 0 and G-CSF once daily beginning on day 0 and
continuing until blood counts recover.

- Cohort 2: Patients receive allogeneic G-CSF-primed bone marrow derived stem cells
on day 0 and G-CSF SC once daily beginning on day 0 and continuing until blood
counts recover.

- Post-transplant CNS prophylaxis (for patients with acute lymphocytic leukemia):
Patients receive standard post-transplant CNS prophylaxis comprising intrathecal
methotrexate.

- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2
hours twice daily beginning on day -1 and, once oral medications are tolerated,
continuing orally twice daily until day 100 followed by a taper until day 180.

Patients with progressive disease on day 28 post-transplantation may undergo donor
lymphocyte infusions (DLI). Immunosuppression is withdrawn and patients receive nonmobilized
DLI IV every 2-4 weeks in the presence of progressive disease and the absence of GVHD.

After completion of study treatment, patients are followed periodically for at least 5
years.

PROJECTED ACCRUAL: A total of 56 patients (10 recipient/donor pairs in cohort 1 and 18
recipient/donor pairs in cohort 2) will be accrued for this study .