TCRαβ-depleted Progenitor Cell Graft With Early Memory T-cell DLI, Plus Selected Use of Blinatumomab, in naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies

Inclusion Criteria:

Recipient:

* Age less than or equal to 21 years
* High risk hematologic malignancy whereas allogeneic transplantation is the current standard of care. This includes (but is not limited to):

  * High risk ALL in CR1 or CR2,
  * any ALL in CR3 or subsequent;
  * AML in high risk CR1 (AML diagnosis includes myeloid sarcoma),
  * any AML in CR2 or subsequent,
  * any therapy related AML;
  * MDS (primary or secondary),
  * NK cell, biphenotypic, or undifferentiated leukemia/lymphoma in CR1 or subsequent;
  * CML in accelerated phase, or in chronic phase with persistent molecular positivity or intolerance to tyrosine kinase inhibitor, or a history of blast crisis.
* If prior CNS leukemia, it must be treated and in CNS CR
* Left ventricular ejection fraction \> 40%, or shortening fraction ≥ 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 ≥ 92% on room air if patient is unable to perform pulmonary function testing
* Karnofsky or Lansky (age dependent) performance score ≥ 50 (See APPENDIX A)
* Bilirubin ≤ 3 times the upper limit of normal for age
* Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age

Donor:

* At least single haplotype matched (≥ 4 of 8) family member
* At least 18 years of age
* HIV negative
* Regarding donation 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

Exclusion Criteria:

Recipient:

* Has a suitable HLA-identical sibling or suitable 12/12 (HLA-A, B, C, DRB1, DQB1, and DPB1) HLA-matched unrelated donor available in an appropriate time frame.
* Any other active malignancy other than the one for which this HCT is indicated
* Received a prior allogeneic HCT at any time
* Received an autologous HCT within the previous 6 months
* Pregnant, if female is of childbearing potential, negative test must be confirmed by serum or urine pregnancy test within 14 days prior to enrollment
* Breast feeding
* Any current uncontrolled bacterial, fungal or viral infection

Donor:

* Pregnant, negative test must be confirmed by serum or urine pregnancy test within 14 days prior to enrollment if female
* If female, breast feeding