Targeting the IPA and Matching for the Non-Inherited Maternal Antigen for Haplo-Cord Transplantation

In this trial, we aim to improve the outcomes of haplo cord transplant. Haplo cord transplant is a novel and promising way to improve transplant outcomes. We hypothesize that identification of a graft that is at least 5/6 matched and inherited paternal antigen (IPA) targeted (i.e., cord blood grafts share one or more IPA antigens with the prospective recipient) is more important to the outcome of haplo cord transplant than the nucleated cell dose. The identification of such a graft for a large proportion of the subjects may necessitate accepting a lower umbilical cord graft dose. In addition to a umbilical cord blood transplant, recipients will receive stem cells from a family member ( a haplo-identical donor) . After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device. The subject will undergo a chemotherapy conditioning regimen prior to transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Subject must have a confirmed diagnosis of:

  1. Previously Relapsed or refractory acute leukemia (myeloid or lymphoid)
  2. Acute leukemia in first remission at high-risk for recurrence
  3. Chronic myelogenous leukemia in chronic, accelerated phase or blast-crisis
  4. Recurrent or refractory malignant lymphoma or Hodgkin lymphoma
  5. Chronic lymphocytic leukemia, relapsed or with poor prognostic features
  6. Multiple myeloma
  7. Myelodysplastic syndrome
  8. Chronic myeloproliferative disease
  9. Hemoglobinopathies
  10. Aplastic anemia
  11. Other hematological disorder in need of allogeneic transplant (e.g. blastoid dendritic cell neoplasm)
* Age ≥ 18 years
* Likely to benefit from allogeneic transplant in the opinion of the transplant physician
* An HLA-identical related or unrelated donor cannot be identified within an appropriate time frame.
* Karnofsky (KPS) Performance status of \>= 70%
* Acceptable organ function as defined below: Serum bilirubin: \< 2.0mg/dL ALT(SGPT): \< 3 X upper limit of normal Creatinine Clearance: \> 50 mL/min/1.73m2 (as estimated by the modified MDRD equation)
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Life expectancy is severely limited by concomitant illness or uncontrolled infection
* Severely decreased Left Ventricular Ejection Fraction (LVEF) or impaired pulmonary function tests (PFT's)
* Evidence of chronic active hepatitis or cirrhosis
* Uncontrolled HIV disease
* Pregnant or lactating

• DERIVEDvan Besien K, Artz A, Champlin RE, Guarneri D, Bishop MR, Chen J, Gergis U, Shore T, Liu H, Rondon G, Mayer SA, Srour SA, Stock W, Ciurea SO. Haploidentical vs haplo-cord transplant in adults under 60 years receiving fludarabine and melphalan conditioning. Blood Adv. 2019 Jun 25;3(12):1858-1867. doi: 10.1182/bloodadvances.2019000200. PMID 31217161
• DERIVEDvan Besien K, Hari P, Zhang MJ, Liu HT, Stock W, Godley L, Odenike O, Larson R, Bishop M, Wickrema A, Gergis U, Mayer S, Shore T, Tsai S, Rhodes J, Cushing MM, Korman S, Artz A. Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival. Haematologica. 2016 May;101(5):634-43. doi: 10.3324/haematol.2015.138594. Epub 2016 Feb 11. PMID 26869630