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

* ELIGIBILITY CRITERIA: INCLUSION CRITERIA: TRANSPLANT RECIPIENT 1. At National Institutes of Health (NIH). Age greater than or equal to 15 years old and/or greater than or equal to 9 years old and pubertal and less than or equal to 55 years for recipient. Pubertal is defined by: prior menses at any time (females), documentation of clinical Tanner stage greater than 2 at some point pre-chemotherapy or at the current visit. (At this point, sex steroids have been produced for a few years which have driven initial pubertal development). Tanner 2 is defined as: breast buds for females with coarse pubic hair, and coarse pubic hair and testes \> 2.5cm for males. 2. At Children's National Medical Center only: age \> 4 years old and \< 24. 3. At University of Oklahoma: Age greater than or equal to 17 years old and less than or equal to 55 years for recipient. 4. A diagnosis of a hematologic malignancy for which stem cell transplant is standard of care: 4.1. Acute Lymphocytic Leukemia (ALL) Adult: (greater than or equal to 22 years) greater than or equal to compete remission 2 (CR2) OR complete remission 1 (CR1) with: * Matched sibling donor for recipient treated on adult leukemia regimen * t(9:22) or bcr-abl+; t(4:11), t(1:19), t(8:14), 11q23 (MLL rearrangements) complex cytogenetics (5 or more chromosomal abnormalities), hypodiploidy (\<44 chromosomes). Note that patients with ALL blast crisis who emerge from chronic myeloid leukemia (CML) are also eligible * Primary induction failure, defined as failure to achieve CR with primary induction chemotherapy * High white blood cell (WBC) (\>30,000 for B-cell ALL and \>100,000 for T-cell ALL) at diagnosis * Persistence of minimal residual disease despite induction chemotherapy Pediatric (\< 22 years): greater than or equal to CR2 OR CR1 with high risk features * Matched sibling donor for recipient treated on adult leukemia regimen * Primary induction failure (M3 (\>25% with greater 200 cells counted) marrow at day 29), M2 (5-25% blasts with greater than 200 cells counted) bone marrow or minimal residual disease (MRD) \> 1% at day 29 who then fail at day 43 with either an M2 or M3 BM or MRD \> 1% * Persistent leukemia and t(9;22) (MRD \>1% day 29 or MRD \> 0.01% end consolidation) * 11q23 (MLL) rearrangements detected by cytogenetic or polymerase chain reaction (PCR) at initial diagnosis who are slow early responders (M2/M3 at day 14 or MRD\> 0.01% at day 29) * Extreme hypodiploidy (\< 44 chromosomes or deoxyribonucleic acid (DNA) index of \<0.81) detected by cytogenetic/ploidy analysis 4.2 Acute Myelogenous Leukemia Adult: (greater than or equal to 22 years) greater than or equal to CR2 OR CR1 with high one of the following risk features -Adverse or intermediate-risk cytogenetics including: 1. Normal cytogenetics 2. complex karyotype (\>2 abnormalities) 3. inv (3) or t (3;3); t(11;19)(q23;p13.1); +13; -17/17p-; -18; -20; (t(6;9); t(6;11); -7, 7q-; -5, 5q-; trisomy 8; t(3;5); t(9:11)(p22q23) 4. monosomy karyotype (presence of an autosomal monosomy in conjunction with at least one other autosomal monosomy or structural abnormality. 5. Any other karyotype EXCEPT t(8;21), t(9;11), inv(16), or t (16;16), and M3 (17; 17) unless ckit mutation present and then eligible. 6. AML emerging from CML (blast crisis) are eligible -Primary induction failure, defined as failure to achieve CR with primary induction chemotherapy * Secondary AML, defined as AML related to antecedent myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), or cytotoxic chemotherapy * Hyperleukocytosis (White blood cell (WBC) \> 100,000 at diagnosis) * Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene (FLT3-LM; FLT-ITDs) * Bilineage or biphenotypic leukemias are high risk features and eligible. Pediatric (\< 22 years): greater than or equal to CR2 OR CR1 with a high risk feature including: -Primary induction failure (greater than or equal to 5% blasts in marrow after induction) * Persistent leukemia (\>15% after first course of chemotherapy) * Complex karyotype, monosomy 7, or -5/-5q, FLT3 ITD-AR (\>0.4) EXCEPT if also inv(16)/t(16;16), t(8,21) * Normal cytogenetics or abnormal cytogenetics EXCEPT if also inv(16)/t(16;16), t(8,21) are eligible for SIBLING transplant only * Bilineage or biphenotypic leukemias are high risk features and eligible. 4.3. Myelodysplastic Syndrome Refractory Anemia with Excess Blasts (RAEB) 1 or 2; cytogenetics showing complex karyotype (3 or more abnormalities), monosomy 7/del(7q), or inv(3)/t(3q)/del(3q); or transfusion dependent. 4.4. Chronic Myelomonocytic Leukemia 4.5. Chronic Myelogenous Leukemia who have failed 2G- tyrosine kinase inhibitors (TKI) 4.6. Standard pediatric indications for myeloablative transplantation for patients undergoing bone marrow transplant at Children's National Medical Center per institutional guidelines 5\. Disease status If patients are found to not be in remission at screening, then the patient may be returned to their primary hematologist/oncologist or may receive chemotherapy as per standard of care for the malignant disease. Patients for whom this would be their first allogeneic transplant must be in remission (\< 5% malignant blasts in marrow and peripheral blood and no evidence of extramedullary disease) for transplant. Patients enrolled on this protocol for their second transplant do not need to have attained remission prior to transplant. 6\. Performance status: Karnofsky or Lansky performance status greater than or equal to 60% AND life expectance of greater than 3 months. 7\. Ability to give informed consent. For recipients and donors \< 18 years of age, their legal guardian must give informed consent. Pediatric patients will be included in an age appropriate discussion in accordance with institutional guidelines. 8 Hepatic function: Patients must have evidence of adequate liver function prior to enrollment defined by total bilirubin \< 2.5 mg/dL (unless documented Gilbert's syndrome) AND transaminases less than or equal to 5 x the upper limit of normal for age appropriate indices. 9\. Renal function: Patients must have evidence of adequate renal function to proceed with stem cell transplant, creatinine clearance \> 60 ml/min/1.73 m(2). Glomerular filtration rate (GFR) may also demonstrate adequate renal function. 10\. Left ventricular ejection fraction greater than or equal to 50% OR shortening fraction of greater than or equal to 27% demonstrated on 2-dimension (2D) echocardiogram or multi-gated acquisition scan (MUGA). 11\. Pulmonary function of Diffusing Capacity of the Lung for Carbon Monoxide (DLC0) adj/alveolar volume (VA) and forced expiratory volume 1 (FEV1) greater than or equal to 60% of normal indices for age and height unless the patient has a likely acute reversible etiology of decline and then DLCO adj/VA greater than or equal to 30% of normal. Pediatric patients unable to complete pulmonary function tests (PFTs) may be enrolled as per enrolling institution Standard Operating Procedure (SOP) for recipient guidelines. 12\. Patients with prior autologous stem cell transplants will be included. Patients with prior allogeneic stem cell transplants will be eligible for 2nd BMT if not previously transplanted with FLT on this study. 13\. Prior experimental systemic therapies must have been completed greater than 2 weeks prior to study entry. EXCLUSION CRITERIA: TRANSPLANT RECIPIENT 1. History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent. 2. Active infections not responding to therapy. All efforts should be made to clear the infection prior to enrollment. 3. Clinically significant systemic illness with manifestations of significant organ dysfunction which in the judgment principal investigator (PI) or associate investigator (AI) would render the patient unlikely to tolerate the protocol therapy or complete the study. 4. Presence of active malignancy from an organ system other than hematopoietic. 5. Human immunodeficiency virus (HIV) infection. 6. Chronic active hepatitis B infection. Patients may be hepatitis B core antibody positive but must be surface antigen negative and without active evidence of disease. 7. Pregnant or lactating females will be excluded from this trial due to unknown risks to the developing fetus. Patients of child-bearing potential must use an effective form of contraception while on study. 8. Sexually active individuals capable of becoming pregnant who are unable or unwilling to use effective form(s) of contraception during time enrolled on study and for 1 year post-transplant. 9. History of prior Leuprolide intolerance. Note: patients ARE eligible if prior or current leuprolide exposure. INCLUSION CRITERIA: MATCHED RELATED TRANSPLANT DONOR 1. Age greater than or equal to 2 and less than or equal to 60 years old and able to give consent or assent. For donors \< 18 years old, the legal guardian must be able to provide informed consent and an evaluation by a Licensed Social Worker (LSW) or psychiatric personnel will be needed to determine willingness to participate. Pediatric patients will be included in an age appropriate discussion in accordance with institutional guidelines. 2. Human leukocyte antigen (HLA)-matched related donor, excluding identical twins. Donors must be matched at least 7 loci out of 8 at the allele or antigen level excluding antigen DRB1 mismatch. 3. Donor selection will be in accordance with National Institutes of Health (NIH)/Clinical Center (CC) Department of Transfusion Medicine criteria and must be able to medically endure stem cell collection or as per local institutional guidelines. 4. Donors must be HIV negative, human T-cell leukemia-lymphoma virus (HTLV) negative, hepatitis B surface antigen (HBsA) negative. 5. Donors must be physically able to and willing to tolerate marrow harvest collection preferably, or in the absence of this option, able and willing to donate via peripheral blood pheresis. EXCLUSION CRITERIA: MATCHED RELATED TRANSPLANT DONOR 1. History of medical illness that in the estimation of the PI or Department of Transfusion Medicine (DTM) physician precludes donation of marrow. 2. Anemia (Hemoglobin (Hb) \< 10 gm/dl) or thrombocytopenia (\< 100,000/ ul). 3. Pregnant females (due to risk to fetus). 4. Current psychiatric diagnosis that would compromise compliance with transplant protocol or precludes appropriate informed consent. 5. Presence of any blood transmissible infectious disease that cannot be cleared prior to stem cell collection and poses an unacceptable risk for the recipient (excludes cytomegalovirus (CMV)). 6. Active malignancy will exclude the donor. Any malignancy less than five years postremission will exclude the donor. Non-hematologic malignancies greater than 5 years ago will not exclude the donor. Any history of hematologic malignancy will be considered on a case by case basis. 7. Any medical contraindication to anesthesia or marrow donation will exclude the donor. 8. Donors receiving experimental therapy or investigational agents. 9. Active autoimmune disease that in the opinion of the PI or AI would compromise the success of the transplant. INCLUSION CRITERIA- MATCHED UNRELATED DONOR 1. Unrelated donor matched at HLA-A, B, C, and DR loci by high resolution typing (at 8/8 or 7/8 antigen/allele match) are acceptable donors. 2. The evaluation of donors shall be in accordance with existing National Marrow Donor Program (NMDP) Standard Policies and Procedures at all institutions. INCLUSION CRITERIA- (18F) FLT CANDIDATE TRANSPLANT RECIPIENT 1. Meets criteria for Transplant Recipient 2. Age greater than or equal to 18 years old at National Cancer Institute (NCI), and age \> 4 years and \< 24 years at Children's National Medical Center 3. Donor who is willing to undergo bone marrow or stem cell harvest. EXCLUSION CRITERIA- (18F) FLT CANDIDATE TRANSPLANT RECIPIENT 1\. History of prior fluorothymidine allergy or intolerance.