Inclusion Criteria:
1. Subjects ≥ 18 and ≤ 67 years old,
2. Patient with either i. High risk acute leukemia or myelodysplasia defined as expected 2 year OS or PFS \< 40% after a conventional allogeneic HSC transplant or ii. A hematologic malignancy requiring an allogeneic hematopoietic stem cell transplant and lack of a suitable HLA identical, haploidentical or 7/8 HLA matched donor.
3. Availability of an adequate CB for expansion:
i. ≥ 5/8 HLA match when A, B, C and DRB1 are performed at the allele level.
ii. Minimal cell dose: TNC ≥ 1.5 x 107/kg, and CD34 ≥ 0.5 x 105/kg. iii. Needs to be erythrodepleted by bank prior to cryopreservation. iv. Must comply with local site regulations AND, come from a cord bank that is FACT, or AABB accredited, or FDA approved or eligible for NMDP IND (unless PI approves another bank).
v. To meet eligibility criteria, the patient's weight at time of cord selection will be used; however, if this weight has increased by more than 5% at time of admission to hospital and with the new weight the patient no longer meets eligibility criteria for cell dose, LI approval will be required to move forward with the selected cord. Every attempt will be made to always use the most recent weight in cord selection
4. Patients with adequate physical function as measured by:
i. Karnofsky score ≥ 70% ii. Hematopoietic comorbidity index (HCT-CI): 0-3 for 2nd transplant and age 60-65 years, 0-5 if \<60 years old, and 0-2 if 66-67 years.
iii. Adequate cardiac function: Left ventricular ejection fraction ≥ 40% within 60 days prior to start of conditioning regimen iv. Adequate pulmonary function: Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and diffusing capacity corrected for hemoglobin (DLCOc) ≥ 50% of predicted within 60 days prior to start of conditioning regimen.
v. Adequate hepatic function: Bilirubin \< 2 x ULN unless felt to be related to Gilbert's disease or hemolysis; AST and ALT ≤ 2.5 x ULN (the PI may approve up to 3 times ULN) ; alkaline phosphatase ≤ 5 x ULN.
vi. Adequate renal function: Estimated or measured creatinine clearance ≥ 60 ml/min/1.73m2.
5. A back up graft must have been identified prior to initiation of conditioning regimen.
6. Signed written informed consent.
7. Female patients of childbearing potential must have a negative serum pregnancy test within 30 days of enrolment and within 30 days of starting of preparative regimen; patient must be willing to use an effective contraceptive method while enrolled in the study.
Exclusion Criteria:
1. Allogeneic or autologous myeloablative transplant within last 6 months.
2. Patients with inadequate physical function as measured by:
i. Active, uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of either progression of clinical symptoms or radiologic findings or lack of evidence of response to therapy).
ii. Presence of a malignancy other than the one for which the HSC transplant is being performed, with an expected survival estimated to be less than 75% at 5 years.
iii. Seropositivity for HIV. iv. Hepatitis B or C infection with measurable viral load. Patients with hepatitis B or C infection regardless of viral load require clear documentation of absence of cirrhosis by either fibroscan or biopsy.
v. Liver cirrhosis.
3. Positive anti-donor HLA antibodies with MFI above 1500 against the selected CB (PI may approve an MFI up to 5000; if above 2500, desensitization is strongly recommended)
4. Use of an investigational agent within 30 days (defined as a drug not approved by Health Canada or FDA regardless of indication) of start of chemotherapy unless documented approval obtained from Sponsor.
5. Presence of ≥30% blasts in bone marrow or ≥ 0.5 x109/L blasts in circulating blood
6. Active central nervous system involvement or chloroma \> 2 cm.
