Pilot Study of Non-Myeloablative, HLA-Matched Allogeneic Stem Cell Transplantation for Pediatric Hematopoietic Malignancies

INCLUSION CRITERIA PATIENTS: Patients with the following diagnoses will be considered: Hodgkin's and Non-Hodgkin's Lymphoma: Refractory (non-CR) to primary treatment regimen; Refractory (non-CR) to or relapse after salvage regimen. Acute Myelogenous Leukemia (AML): History of bone marrow relapse it CR number 2 or greater. Acute Lymphocytic Leukemia (ALL): History of bone marrow relapse in CR number 2 or greater; complete remission #1 with Philadelphia chromosome positive or prior induction failure (subsequent induction regimen required to achieve CR). Acute hybrid leukemia including mixed lineage, biphenotypic, and undifferentiated (AUL): History of bone marrow relapse in CR number 2 or greater; Complete remission #1 with Philadelphia chromosome positive or prior induction failure (second induction regimen required to achieve (CR). Myelodysplastic Syndrome (MDS) excluding refractory anemia (RA) and RA with ringed sideroblasts (RARS): blasts less than 10% in marrow and blood. Chronic Myelogenous Leukemia (CML): Chronic Phase; Accelerated Phase with blasts less than 10% in marrow and blood. Juvenile Myelomonocytic Leukemia (JMML, J-CML): Blasts less than 10% in marrow and blood. Patients must be greater than or equal to 4 years and less than 22 years of age. Prior chemotherapy: Chemotherapy to achieve above noted criteria allowed. Prior autologous BMT allowed. Prior allogeneic BMT allowed as long as at least day +100 post-prior BMT, and no evidence of ongoing active GVHD. Availability of 5 or 6 antigen genotypic HLA-matched first-degree relative donor (single HLA-A or B locus mismatch allowed). Performance status of 0,1, or 2. 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 2.5 times the upper limit of normal. Values above these levels may be accepted, at the discretion of the PI, if such elevations are thought to be due to malignancy (excluding acute leukemia). Renal function: age-adjusted normal serum creatinine or a creatinine clearance greater than or equal to 60 mL/min/1.73 m(2). Pulmonary function: DLCO corrected for hemoglobin and alveolar volume greater than or equal to 50% of predicted. Left ventricular function: Ejection fraction greater than or equal to 45% by MUGA or shortening fraction greater than or equal to 28% by ECHO. Ability to give informed consent. For patients less than 18 years old their legal guardian must give informed consent. Pediatric patients will be included in age appropriate discussion in order to obtain verbal assent. Durable power of attorney form completed (patients greater than 18 years of age only). Patients must not have an active CNS malignancy as defined by: lymphoma (tumor mass on CT scan or leptomeningeal disease), Leukemia (CNS 2 or CNS 3 classification), or NB (History of CNS involvement with no current evidence of CNS malignancy is NOT an exclusion). Patients must not be HIV positive. Patients must not have active hepatitis B or C infection as defined by seropositive for hepatitis B (HbSAg) or hepatitis C and elevated liver transaminases. Female patients must not be lactating or pregnant (due to risk to fetus or newborn). Patients must not have high risk of inability to comply with transplant protocol as determined by principal investigator, social work, and BMT team. Patients must not have Fanconi Anemia (FA): patients with MDS must have a negative FA test. INCLUSION CRITERIA DONOR: First degree relative with genotypic identity at 5 or 6 HLA loci (single HLA-A or B locus mismatch allowed). Weight of greater than or equal to 15 kilograms. Adequate venous access for peripheral apheresis, or consent to use a temporary central venous catheter for apheresis (on Cohort #2, for possible future cell collection if needed). Ability to give informed consent. For donors less than 18 years of age, he/she must be the oldest eligible donor, their legal guardian must give informed consent, the donor must give verbal assent, and he/she must be cleared by social work and a mental health specialist to participate. Donor selection criteria will be in accordance with NIH/CC Department of Transfusion Medicine standards. EXLCUSION CRITERIA PATIENT: Active CNS malignancy as defined by: Lymphoma: tumor mass on CT scan or leptomeningeal disease Leukemia: CNS 2 or CNS 3 classification NB: History of CNS involvement with no current evidence of CNS malignancy is NOT an exclusion. HIV positive. Active hepatitis B or C infection as defined by seropositive for hepatitis B (HbsAg) or hepatitis C and elevated liver transaminases. Lactating or pregnant females. High risk of inability to comply with transplant protocol as determined by principal investigator, social work, and BMT team. Fanconi Anemia (FA): Patients with MDS must have a negative FA test. EXCLUSION CRITERIA DONOR: History of medical illness which in the estimation of the PI or DTM physician poses prohibitive risk to donation including, but not limited to stroke, hypertension that is not controlled by medication, or heart disease. Individuals with symptomatic angina or a history of coronary artery bypass grafting or angioplasty will not be eligible. History of congenital hematologic, immunologic, or metabolic disorder which in the estimation of the PI poses prohibitive risk to the recipient. Anemia (Hb less than gm/dl) or thrombocytopenia (less than 100,000/ul). Lactating or pregnant females. HIV positive. Seropositive for hepatitis B (HbsAg) or hepatitis C. High risk of inability to comply with transplant protocol as determined by principal investigator, social work, and BMT team.