Background:~Allogeneic blood and marrow stem cell transplantation (BMT) plays an important role in the curative treatment of a number of pediatric malignancies. Unfortunately, the success of conventional allogeneic BMT is limited in part by the multiple toxicities associated with myeloablative preparative regimens.~Non-myeloablative pre-transplant regimens are associated with less toxic side effects than standard BMT. Recently, a novel immunosuppressive, non-myeloablative pre-transplant chemotherapy regimen has been shown to facilitate complete donor engraftment in an adult trial at the NCI.~Objectives:~The primary objective of this protocol is to evaluate the efficacy and safety of this treatment approach in pediatric patients with hematopoietic malignancies~Eligibility:~Inclusion Criteria~Age: Patient must be greater than or equal to 5 years and less than 22 years of age.~Diagnosis:~Hodgkin s and Non-Hodgkin s Lymphoma: Refractory disease or relapse after salvage regimen.~Acute Myelogenous Leukemia: History of bone marrow relapse in remission (CR) #2 or greater.~Acute Lymphocytic Leukemia: History of bone marrow relapse in CR #2 or greater (CR#1 with Philadelphia chromosome positive or prior induction failure).~Acute Hybrid Leukemia including mixed lineage, biphenotypic and undifferentiated: History of bone marrow relapse in CR #2 or greater (CR#1 with Philadelphia chromosome positive or prior induction failure).~Myelodysplastic Syndrome: RAEB or RAEB-t with less than 10% blasts in marrow and blood.~Chronic Myelogenous Leukemia: Chronic phase or accelerated phase with less than 10% blasts in marrow and blood.~Juvenile Myelomonocytic Leukemia: less than 10% blasts in marrow and blood.~Prior Therapy: Chemotherapy to achieve above criteria allowed. Prior BMT allowed as long as at least day 100+ post-prior BMT, no evidence of GVHD, and no detectable residual donor chimerism.~Donor: First degree related donors, who are HLA matched (single HLA-A or B locus mismatch allowed), weight greater than or equal to 15 kilograms, and who meet standard donation criteria will be considered. The same donor from a prior BMT is allowed.~ECOG Performance Status: 0, 1, or 2. and life expectancy: greater than 3 months.~Liver Function: Serum direct bilirubin less than 2.0 mg/dL and serum ALT and AST values less than or equal to 2.5x upper limit of normal. (Values above these levels may be accepted if due to malignancy.)~Renal Function: Age adjusted normal serum creatinine or Cr clearance greater than or equal to 60 mL/min/1.73 m(2).~Pulmonary Function: DLCO greater than or equal to 50%.~Cardiac Function: LVEF greater than or equal to 45% by MUGA or LVSF greater than or equal to 28% by ECHO~Exclusion Criteria~Active CNS malignancy: Tumor mass on CT or leptomeningeal disease. (Patients with a history of CNS involvement and no current evidence of CNS disease are allowed.)~HIV infection, active hepatitis B or C infection: HbSAg or HCV seropositive and elevated liver transaminases.~Fanconi Anemia.~Lactating or pregnant females.~Design:~Pilot Study~Initial evaluation: Patient and donor will be screened for eligibility. G-CSF primed bone marrow derived stem cells will be collected from the donor.~Induction/Consolidation chemotherapy: 1 to 3 cycles will be given every 22 days depending on disease response, CD4 count, and toxicities.~Lymphoma: fludarabine, etoposide, doxorubicin, vincristine, cyclophohamide, prednisone, and filgrastim (EPOCH-fludarabine).~Leukemia and MDS: Fludarabine, cytarabine, and filgrastim (FLAG).~Transplantation: Fludarabine and cyclophosphamide will be administered over 4 days followed by bone marrow transplant. Patients will remain hospitalized until bone marrow recovery. Patients will be monitored closely at the NIH for at least 100 days post-BMT.~Post-transplant CNS prophylaxis for ALL: Standard post-transplant CNS prophylaxis will be employed with intrathecal methotrexate to decrease the risk of CNS relapse for all patients with ALL.~Total number of recipient and donors to be accrued is 56.
Background:~Allogeneic blood and marrow stem cell transplantation (BMT) plays an important role in the curative treatment of a number of pediatric malignancies. Unfortunately, the success of conventional allogeneic BMT is limited in part by the multiple toxicities associated with myeloablative preparative regimens.~Non-myeloablative pre-transplant regimens are associated with less toxic side effects than standard BMT. Recently, a novel immunosuppressive, non-myeloablative pre-transplant chemotherapy regimen has been shown to facilitate complete donor engraftment in an adult trial at the NCI.~Objectives:~The primary objective of this protocol is to evaluate the efficacy and safety of this treatment approach in pediatric patients with hematopoietic malignancies~Eligibility:~Inclusion Criteria~Age: Patient must be greater than or equal to 5 years and less than 22 years of age.~Diagnosis:~Hodgkin s and Non-Hodgkin s Lymphoma: Refractory disease or relapse after salvage regimen.~Acute Myelogenous Leukemia: History of bone marrow relapse in remission (CR) #2 or greater.~Acute Lymphocytic Leukemia: History of bone marrow relapse in CR #2 or greater (CR#1 with Philadelphia chromosome positive or prior induction failure).~Acute Hybrid Leukemia including mixed lineage, biphenotypic and undifferentiated: History of bone marrow relapse in CR #2 or greater (CR#1 with Philadelphia chromosome positive or prior induction failure).~Myelodysplastic Syndrome: RAEB or RAEB-t with less than 10% blasts in marrow and blood.~Chronic Myelogenous Leukemia: Chronic phase or accelerated phase with less than 10% blasts in marrow and blood.~Juvenile Myelomonocytic Leukemia: less than 10% blasts in marrow and blood.~Prior Therapy: Chemotherapy to achieve above criteria allowed. Prior BMT allowed as long as at least day 100+ post-prior BMT, no evidence of GVHD, and no detectable residual donor chimerism.~Donor: First degree related donors, who are HLA matched (single HLA-A or B locus mismatch allowed), weight greater than or equal to 15 kilograms, and who meet standard donation criteria will be considered. The same donor from a prior BMT is allowed.~ECOG Performance Status: 0, 1, or 2. and life expectancy: greater than 3 months.~Liver Function: Serum direct bilirubin less than 2.0 mg/dL and serum ALT and AST values less than or equal to 2.5x upper limit of normal. (Values above these levels may be accepted if due to malignancy.)~Renal Function: Age adjusted normal serum creatinine or Cr clearance greater than or equal to 60 mL/min/1.73 m(2).~Pulmonary Function: DLCO greater than or equal to 50%.~Cardiac Function: LVEF greater than or equal to 45% by MUGA or LVSF greater than or equal to 28% by ECHO~Exclusion Criteria~Active CNS malignancy: Tumor mass on CT or leptomeningeal disease. (Patients with a history of CNS involvement and no current evidence of CNS disease are allowed.)~HIV infection, active hepatitis B or C infection: HbSAg or HCV seropositive and elevated liver transaminases.~Fanconi Anemia.~Lactating or pregnant females.~Design:~Pilot Study~Initial evaluation: Patient and donor will be screened for eligibility. G-CSF primed bone marrow derived stem cells will be collected from the donor.~Induction/Consolidation chemotherapy: 1 to 3 cycles will be given every 22 days depending on disease response, CD4 count, and toxicities.~Lymphoma: fludarabine, etoposide, doxorubicin, vincristine, cyclophohamide, prednisone, and filgrastim (EPOCH-fludarabine).~Leukemia and MDS: Fludarabine, cytarabine, and filgrastim (FLAG).~Transplantation: Fludarabine and cyclophosphamide will be administered over 4 days followed by bone marrow transplant. Patients will remain hospitalized until bone marrow recovery. Patients will be monitored closely at the NIH for at least 100 days post-BMT.~Post-transplant CNS prophylaxis for ALL: Standard post-transplant CNS prophylaxis will be employed with intrathecal methotrexate to decrease the risk of CNS relapse for all patients with ALL.~Total number of recipient and donors to be accrued is 56.