Pilot Study of Leuprolide to Improve Immune Function After Allogeneic Bone Marrow Transplantation

Background: * Impaired lymphocyte immune reconstitution is associated with morbidity and mortality following allogeneic bone marrow transplant (BMT). * Data suggest that one of the limitations of immunity after BMT is the lack of thymus recovery and proper B cell development. * Androgen withdrawal has been shown to enhance T and B lymphopoiesis. * Leuprolide is an approved, safe, gonadotropin releasing hormone (GnRH) agonist/antagonist. * Noninvasive imaging modalities to study immune reconstitution would be invaluable to predict optimal or impaired immune recovery permitting early institution of therapies. * FLT is 3-deoxy-3 18F-fluorothymidine, a radiolabeled thymidine analogue that illustrates dividing hematopoietic cells and may predict immune recovery after allogeneic BMT. * FLT has been used safely in patients who have received intensive chemotherapy. Objectives: * Primary: To determine if leuprolide improves B lymphocyte reconstitution after first BMT. * Primary: To assess whether 18F FLT positron emission tomography (PET)/computed tomography (CT) could predict early engraftment/immune reconstitution in marrow and thymus after allogeneic BMT. * Primary: To assess safety of leuprolide after 2nd BMT evaluated in a separate arm. Eligibility: * Patients \> 9 years old and pubertal and/or \>15 year and less than or equal to 55 years, with aggressive leukemia (Acute Myelogenous Leukemia (AML), myelodysplastic syndromes (MDS) with high risk cytogenetics, Acute Lymphocytic Leukemia (ALL), CMML, certain CML) requiring BMT will be enrolled at National Cancer Institute (NCI). * At University of Oklahoma, Age \> 17 years old and less than or equal to 55 years for recipient. * Patients \> 4 and \< 24 years with the above diseases will be enrolled at Children's National Medical Center (CNMC). Design: * This is a prospective pilot study, the primary aims of which are: 1) to assess whether leuprolide enhances lymphocyte recovery after first BMT, 2) whether FLT imaging can be used to predict engraftment/immune reconstitution after first transplant, and 3) whether leuprolide and FLT are tolerable for second HSCT. * At NCI and Univ of Oklahoma, post-pubertal pediatric male patients (\<18 years) will be randomized to receive a 3 month (11.25 mg) injection and adult male patients will be randomized to receive 4-month preparation of leuprolide (30 mg) or placebo two weeks before the preparative regimen for first BMT. Women and all individuals undergoing 2nd BMT will receive leuprolide at these doses per age and be evaluated in the treated cohort. At Children's National Medical Center, the patients will not receive leuprolide outside of the context of clinical care and will receive myeloablative BMT as per standard of care with FLT imaging for engraftment as the only primary endpoint. * A target of 68 evaluable adult patients will be enrolled on this trial, which may necessitate up to 118 patients (118 donors) enrolled to reach this target at NCI and University of Oklahoma. A total of 10 pediatric patients will be enrolled at Children's National Medical Center for FLT imaging only. Sixteen patients will be enrolled to undergo second BMT. * At NCI, adults greater than 18 years old both female and adult male patients undergoing 2nd BMT will receive 4-month preparation of leuprolide (30 mg) two weeks before the preparative regimen. All patients will undergo FLT imaging to evaluate whether this may predict BMT response or failure (relapse). This will be a pilot arm of 16 patients total. * The planned length of this trial is 7 years with interim analyses at day 100 and day 365. * Some of the patients are anticipated to be evaluated using FLT (to include only patients needed for the immunological primary endpoint, not increasing total patient numbers). 23 adult NCI patients in total will undergo FLT PET/CT imaging on day -1, at day +5 or day +9, at 4 weeks, and at a future point to include evidence of graft-versus-host disease (GVHD) relapse, or immune recovery. An estimated 50 patients (including subset of the 23 patients undergoing serial scanning) will be imaged approximately at 1 year for evaluation of thymus reconstitution. The total possible numbers will include no more than 118 patients to achieve the 68 evaluable adults for the immunological primary endpoint. However, all 23 FLT PET/CT imaged NCI patients will undergo a single 1 year FLT for evaluation of thymus reconstitution. Up to 10 pediatric patients at CNMC will undergo FLT PET/CT imaging on Day -1, day+9, and day +28 (if possible). Initial images will be correlated with engraftment and other secondary endpoints.