Combined T Cell Depleted Haploidentical Peripheral Blood Stem Cell and Unrelated Umbilical Cord Blood Transplantation in Patients With Hematologic Malignancies Using a Total Lymphoid Irradiation Based Preparative Regimen

Inclusion Criteria-Transplant Recipient:

* Age less than or equal to 21 years old.
* Does not have a suitable matched related/sibling donor (MSD) or volunteer matched unrelated donor (MUD) available in the necessary time for stem cell donation.
* Has a suitable partially human leukocyte antigen (HLA)-matched (≥ 3 of 6) family member donor.
* Has a partially HLA-matched single umbilical cord blood (UCB) unit (≥ 4 of 6) with adequate cell dose. UCB units must fulfill eligibility as outlined in 21 CFR 1271 and agency guidance.
* High-risk hematologic malignancy.

  * High risk acute lymphocytic leukemia (ALL) in complete remission-1 (CR)1. \[Examples include, but not limited to t(9;22), hypodiploid,, M2 or greater marrow at the end of induction, infants with mixed lineage leukemia (MLL) fusion or t(4;11)\].
  * ALL in High risk CR2. \[Examples include but not limited to t(9;22), bone marrow (BM) relapse \<36 mo CR1, T-ALL, very early (\< 6mo CR1) isolated central nervous system (CNS) relapse.\]
  * ALL in CR3 or subsequent.
  * Acute myeloid leukemia (AML) in high risk CR1. \[Examples include but not limited to preceding MDS, 5q-, -5, -7, FAB M6, FAB M7 not t(1;22), minimal residual disease (MRD) ≥ 5% on day 22 (AML08), M3 marrow after induction 1, M2 marrow after two cycles of induction, FLT3-ITD.\]
  * AML in CR2 or subsequent.
  * Therapy related AML, with prior malignancy in CR \> 12mo
  * Myelodysplastic syndrome (MDS), primary or secondary
  * Natural killer (NK) cell, biphenotypic, or undifferentiated leukemia in CR1 or subsequent.
  * Chronic myeloid leukemia (CML) in accelerated phase, or in chronic phase with persistent molecular positivity or intolerance to tyrosine kinase inhibitor.
  * Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous hematopoietic cell transplantation (HCT), or unable to mobilize stem cells for autologous HCT.
  * Non-Hodgkin lymphoma in CR2 or subsequent.
  * Juvenile myelomonocytic leukemia (JMML).
  * Refractory hematologic malignancies \[ALL, AML, chronic myeloid leukemia (CML) in blast crisis, Hodgkin or non-Hodgkin lymphoma\] due to chemoresistant relapse or primary induction failure.
  * All patients with evidence of CNS leukemia must be treated and be in CNS CR to be eligible for study.
* Patient must fulfill pre-transplant evaluation:

  * Cardiac Function: Left ventricular ejection fraction (LVEF) ≥ 40% or shortening fraction (SF) ≥ 25%.
  * Creatinine clearance (CrCL) or glomerular filtration rate (GFR) ≥ 50 ml/min/1.73m2.
  * Forced vital capacity (FVC) ≥ 50% of predicted value or pulse oximetry (Pox) ≥ 92% on room air.
  * Karnofsky or Lansky performance score ≥ 50.
  * Bilirubin ≤ 3 times the upper limit of normal for age.
  * Alanine aminotransferase (ALT) ≤ 5x the upper limit of normal for age.
  * Aspartate aminotransferase (AST) ≤ 5x the upper limit of normal for age.

Exclusion Criteria - Transplant Recipient:

* Patient has a suitable MSD, volunteer matched unrelated donor (MURD), or killer-immunoglobulin receptors (KIR) mismatched haploidentical donor available in the necessary time for stem cell donation.
* Patient has any other active malignancy other than the one for which HCT is indicated.
* Patient is pregnant as confirmed by positive serum or urine pregnancy test within 14 days prior to enrollment.
* Patient is breast feeding.
* Patient has Down Syndrome.
* Patient has a current uncontrolled bacterial, fungal, or viral infection per the judgment of the principal investigator.

Inclusion criteria - haploidentical donor

* At least single haplotype matched (≥ 3 of 6) family member
* At least 18 years of age.
* Human immunodeficiency virus (HIV) negative.
* Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female).
* Not breast feeding.
* Regarding eligibility, is identified as either:

  * Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR
  * Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271.