5 Clinical Trials for Various Conditions
This is an observational study to collect information by use of performance-based measures and survey questionnaires. It does not include interventions aimed at altering patient outcome. Advances in pediatric hematopoietic stem cell transplantation (SCT) have resulted in improved survival and prompted increased attention to the potential adverse late effects of this procedure. Survivors of SCT are thought to be at risk for neurocognitive deficits as a result of their exposure to a number of potentially neurotoxic agents. Prior studies done by our group and others have demonstrated generally stable cognitive function in the first 5 years following transplant, with little evidence of significant declines. However, there has been almost no research to date on the status of very long-term (\> 5 years post-transplant) survivors. In this study, we will evaluate a large sample of long-term survivors of allogeneic SCT using measures of intelligence, academic achievement, and specific cognitive functions such as attention, working memory and processing speed. We will also obtain measures of behavioral functioning and quality of life. We will examine how this group of survivors are functioning relative to normative expectations, and in comparison to community controls without a history of serious illness, matched on age, gender, race/ethnicity, and socioeconomic status. We will also examine the relationship between cognitive function and psychosocial function and quality of life in this population.
OBJECTIVES: I. Determine the effectiveness of moderate dose cyclophosphamide and radiotherapy in terms of improving survival and reducing the morbidity following allogeneic bone marrow transplantation in patients with myelodysplastic syndrome and acute leukemia related to Fanconi's anemia.
RATIONALE: Peripheral stem cell transplantation may be an effective treatment for leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia that has relapsed following bone marrow transplantation. PURPOSE: Phase I/II trial to study the effectiveness of decitabine and peripheral stem cell transplantation in treating patients who have leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia that has relapsed after bone marrow transplantation.
The purpose of this research study is to compare the survival rates of patients with better risk disease undergoing hematopoietic stem cell transplant (HSCT) to the survival rates reported in the medical literature of similar patients undergoing reduced intensity HSCT from matched related donors.
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.