Myeloablative Haploidentical BMT With Post-transplant Cyclophosphamide for Pediatric Patients With Hematologic Malignancies

Inclusion Criteria:

Patient age 0.5-25years
Patients must have a first-degree related donor or half-sibling who is at minimum HLA haploidentical. The donor and recipient must be identical at 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 6-8 weeks from referral to transplant or a low-likelihood of finding a matched, unrelated donor. Patients with an eligible HLA-matched RELATED should not be enrolled on this trial.
Patients must have at least one of the following high-risk conditions listed below:
Acute lymphocytic leukemia (ALL) in 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 FLT3/ITD+, 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 Children's Oncology Group (COG) AAML1031 study 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 Leukemia in 2nd or subsequent CR (CR>2)
Mixed phenotype/Undifferentiated Leukemia in 1st or subsequent CR*
Secondary or therapy related leukemia in CR > 1
Natural Killer (NK) cell lymphoblastic leukemia CR > 1
Myelodysplastic syndrome (MDS)
Juvenile myelomonocytic leukemia (JMML) (patients are eligible if they are not eligible for COG1221 study)
Prior transplant eligible if < 18yo, >6 months has elapsed since BMT, and patient is off immunosuppression for > 3 months with no Graft versus host disease (GVHD)
No known active Central nervous system (CNS) involvement or extramedullary involvement by malignancy. Such disease treated into remission is permitted.
Acute Leukemia - 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.

Exclusion Criteria:

Poor cardiac function: left ventricular ejection fraction <45% as determined by Multigated acquisition scan (MUGA) or Echocardiogram (ECHO). For pediatric patients Left ventricular ejection fraction (LVEF) <45% or a shortening fraction below normal limits for age.
Symptomatic pulmonary disease. Poor pulmonary function: Forced expiratory volume (FEV1), Forced vital capacity (FVC), and Diffusing capacity for carbon monoxide (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 Pulmonary function tests (PFTs) because of developmental stage pulse oximetry < 92% on Room air (RA).
Poor liver function: bilirubin >2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy). Alanine aminotransferase (ALT) or Aspartate transaminase (AST) > 3 x laboratory upper normal limits.
Poor renal function: Creatinine >2.0mg/dl or creatinine clearance (calculated creatinine clearance is permitted) < 60 mL/min based on Traditional Cockcroft-Gault formula: 140 - age (yrs) x Smaller of Actual Weight vs. Ideal Body Weight (kg) / 72 x Serum creatinine (mg/dl) Multiply by another factor of 0.85 if female Intended for ages 18-110, serum creatinine 0.6-7 mg/dl 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.
Schwartz equation: CrCl (ml/min/1.73m2)=[length (cm) x k] /serum creatinine K = 0.45 for infants 1 to 52 weeks old k = 0.55 for children 1 to 13 years old k = 0.55 for adolescent females 13-18 years old k = 0.7 for adolescent males 13-18 years old
HIV-positive
Positive leukocytotoxic crossmatch Specifically, complement dependent cytotoxicity and flow cytometric crossmatch assays must be negative, and the mean fluorescence intensity (MFI) of any anti-donor HLA antibody by solid phase immunoassay should be <3000. Consult with PI for the clinical significance of any anti-donor antibody.
Women of childbearing potential who currently are pregnant (HCG+) or who are not practicing adequate contraception or who are breastfeeding
Uncontrolled viral, bacterial, or fungal infections (currently taking medication and have progression of clinical symptoms)
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