Chemotherapy before and after Donor Bone Marrow Transplant in Treating Younger Patients with Hematologic Cancer

Inclusion Criteria

• Lack of a suitable human leukocyte antigen (HLA)-matched related donor
• Patients must have a first-degree related donor or half-sibling who is at minimum HLA haploidentical to be enrolled; the donor and recipient must be identical at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1; a minimum match of 5/10 is therefore required, and will be considered sufficient evidence that the donor and recipient share one HLA haplotype
• An unrelated donor search is not required for a patient to be eligible for this protocol, or a donor search and donor mobilization may be abandoned if the clinical situation dictates an urgent transplant; clinical urgency is defined as high likelihood that greater 6-8 weeks will be required to proceed to transplant or a low-likelihood of finding a matched, unrelated donor
• Patients must have at least one of the following high-risk conditions listed below (criteria are consistent with existing criteria within Children's Oncology Group [COG] protocols): * Acute lymphocytic leukemia (ALL) in first complete remission (CR1) as defined by at least one of the following: ** Hypodiploidy ** Induction failure ** Minimal residual disease (MRD) after consolidation * Acute myeloid leukemia (AML) in CR1 with high risk features defined as: ** High allelic ratio fms-related tyrosine kinase 3 (FLT3)/internal tandem duplications (ITD) positive (+) ** Monosomy 7 ** Del (5q) ** Standard risk cytogenetics with positive minimal residual disease at the end of Induction I chemotherapy (for patients being treated on or according to COG AAML1031 who have had MRD studies sent to Seattle or performed at their local institution where the flow assay is sensitive enough to detect >= 0.1% blasts) * Acute leukemias in 2nd or subsequent complete remission (CR) (CR >= 2) * Mixed phenotype/undifferentiated leukemias in 1st or subsequent CR * Secondary or therapy related leukemias in CR >= 1 * Natural killer (NK) cell leukemia or NK cell lymphoblastic leukemia/lymphoma CR >= 1 * Myelodysplastic syndrome (MDS) * Juvenile myelomonocytic leukemia (JMML) (patients are eligible if they are not eligible for COG1221) * Prior transplant eligible if =< 18 years old (yo), >= 1 year has elapsed since BMT, and patient is off immunosuppression for >= 3 months with no GVHD; patients who have had a prior chemotherapy based preparative regimen are allowed to receive a TBI based prep, regardless of their disease * No known active central nervous system (CNS) involvement or extramedullary involvement by malignancy; such disease treated into remission is permitted * Remission is defined as morphology with < 5% blasts with no morphological characteristics of acute leukemia (e.g., Auer Rods) in a bone marrow with > 20% cellularity
• DONOR: Age >= 0.5 years
• DONOR: Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FACT)
• DONOR: The following criteria, in order of importance, should also be used for donor selection: * Medically and psychologically fit and willing to donate * The patient must lack antibodies against donor HLA molecules potentially clinically significant * ABO compatibility (in order of priority) ** Compatible or minor ABO incompatibility ** Major ABO incompatibility * Cytomegalovirus (CMV) status ** For a CMV seronegative recipient, use a CMV seronegative donor ** For a CMV seropositive recipient, use a CMV seropositive donor
• DONOR: If there is more than one donor option based on the above criteria, additional suggested criteria to consider (in no order of priority as none of these characteristics have been shown to make a difference in the setting of haploBMT with post-transplantation cyclophosphamide [PT/Cy]) include: * Younger adults age >= 18 years and non-obese donors should be preferred * If all else is equal, male donors may be preferred over nulliparous female donors who may be preferred over multiparous female donors * If all other criteria equal and if the patient and family express a strong preference for a particular donor, that donor should be selected

Exclusion Criteria

• Patients will not be excluded on the basis of sex, racial or ethnic background
• Poor cardiac function: left ventricular ejection fraction < 50% as determined by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) or a shortening fraction below 27%
• Poor pulmonary function: * For patients receiving a TBI based preparative regimen: forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin [Hgb]) =< 60% by pulmonary function tests (PFTs) * For patients receiving a non-TBI based preparative regimen: FEV1, FVC, and DLCO =< 50% predicted (corrected for hemoglobin) for patients who have not received thoracic or mantle irradiation * For patients who have received thoracic or mantle irradiation, FEV1 and FVC < 70% predicted or DLCO =< 50 of predicted; for children unable to perform PFTs because of developmental stage pulse oximetry =< 92% on room air (RA): no evidence of dyspnea at rest, no exercise intolerance * For children who are unable to cooperate for PFTs, required criteria are: no evidence of dyspnea at rest, no exercise intolerance, and not requiring supplemental oxygen therapy
• Poor liver function defined as bilirubin >= 2 mg/dl (not due to hemolysis, Gilbert’s or primary malignancy) or
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >= 3 x laboratory upper normal limits
• Creatinine clearance (calculated creatinine clearance is permitted) < 60 mL/min based on Traditional Cockcroft-Gault formula * For patients < 18 years: creatinine clearance (CrCl) will be estimated by the Schwartz formula; a measured CrCl or a glomerular filtration rate (GFR) may be substituted to determine the subject’s CrCl
• Human immunodeficiency virus (HIV)-positive
• Positive leukocytotoxic crossmatch; specifically, complement dependent cytotoxicity and flow cytometric crossmatch assays must be negative, and the mean (or median) fluorescence intensity (MFI) of any anti-donor HLA antibody by solid phase immunoassay should be < 2000; if a screening assay against pooled HLA antigens is used, positive results must be followed with specificity testing using a single antigen assay; the MFI must be < 2000 unless the laboratory has validated higher threshold values for reactivity for HLA antigens, such as HLA-C, DQ, and DP, that may be enhanced in concentration on the single antigen assays; consult with principal investigator (PI) for the clinical significance of any anti-donor antibody
• Women of childbearing potential who currently are pregnant (beta-human chorionic gonadotropin [HCG]+) or who are not practicing adequate contraception or who are breastfeeding
• Uncontrolled viral, bacterial, or fungal infections (currently taking medication and with progression of clinical symptoms or findings); patients with symptoms consistent with respiratory syncytial virus (RSV), influenza A, B, or parainfluenza at the time of enrollment will be assayed for the above viruses and if positive are not eligible for the trial until they are no longer symptomatic (patients may have continued assay positivity for a period of time post resolution of symptoms secondary to the nature of the assay)