Cord Blood With T-Cell Depleted Haplo-identical Peripheral Blood Stem Cell Transplantation for Hematological Malignancies

Inclusion Criteria

Note: protocol eligible patients according to the criteria outlined below will then be divided according to age, diagnosis, performance status, organ function, prior transplantation, hematopoietic cell transplant comorbidity index (HCT-CI)23, and CB TNC dose into those who are at standard risk (Arm A) or high risk (Arm B) for early post-transplant death for the purposes of applying stopping rules and outcome analysis.

Age:

o 2 - 70 years. Diagnosis of severe aplastic anemia: eligibility to be discussed with PI and Service Chief. Such patients will be assessed in Arm B.

Diagnosis of high risk hematological malignancy:

Any acute leukemia in first complete remission (CR) considered at high risk for relapse, or second or third CR, or relapse/refractory less than 10% blasts in bone marrow, or aplasia post-therapy. This includes de novo acute leukemia or acute leukemia that is therapy related or arising from an antecedent hematologic disorder including myelodysplasia (MDS), chronic myeloid leukemia (CML) or other myeloproliferative disorder.

• Juvenile myelomonocytic leukemia (JMML) in CR, or relapse with less than 10% bone marrow blasts.
• CML with tyrosine kinase inhibitor failure in chronic or accelerated phase or evolved to acute leukemia.
• MDS or other myeloproliferative disorder with life-threatening cytopenia(s), and/or red blood cell or platelet transfusion dependence, or patients with aplasia, or patients with excess blasts less than 10% blasts in the bone marrow at work-up.
• Aggressive lymphoma: patients in CR1 with disease at high risk of relapse or CR2-3.
• Indolent lymphoma or chronic lymphocytic leukemia (CLL): any disease status provided any transformed component is in CR.
• Hodgkin's lymphoma that is primary refractory or relapsed not suitable for other therapy and in PR or CR or small volume stable disease.

Performance status:

• Karnofsky score ≥ 70 or Lansky score ≥ 70.
• Organ function:
• Resting left ventricular ejection fraction (LVEF) ≥ 50%.
• Spirometry (FEV1 and FVC) & corrected DLCO ≥ 50% predicted. In small children use history and physical and CT scan to determine pulmonary status.
• Total bilirubin ≤ to 1.5 mg/dl (unless benign congenital elevated bilirubin); ALT ≤ 3 x upper limit of normal (ULN).
• Calculated creatinine (calc. creat.) clearance ≥ to 60 ml/min.
• Albumin ≥ 3.0.

Graft:

o Cryopreserved dose will be ≥ 1.5 x 10^7 TNC/kilogram in each unit for double unit CB grafts. This will be the CB graft for the majority of patients.

In select patients with access to CB units that have high TNC (> 5.0 x 10^7/kg), and are from good quality CB banks a single unit could be considered with a back-up CB unit on standby.

• In select patients who have a very poor search and only have one suitable CB unit available, this unit could be given as a single unit. This unit must have a TNC ≥ 2.0 x 10^7 TNC/kilogram and a CD34+ cell dose ≥ 1.5 x 10^5 CD34+/kilogram.
• Haploidentical donors who are 5/10 or better but not HLA-identical will be used as outlined in section 6.4.

Assignment of conditioning intensity (high dose vs reduced intensity) will be based on patient disease status, age, extent of prior therapy, organ function and presence of significant comorbidities as outlined in Section 9.2.

For the purposes of analysis (not assignment of preparative regimen), patients will be assigned to Arms A and B as summarized below according to their risk of early post-transplant death.

Eligible patients who fulfill all of the following criteria will be assigned to risk Arm A:

Age 2-49 years Diagnosis Any acute leukemia in CR1 - CR2 (includes therapy-related and arising from MDS or myeloproliferative disease). JMML in CR. CML with TKI failure & 25 kg in weight.

Haploidentical Donor Exclusion Criteria:

Evidence of active infection (including active urinary tract infection, or upper respiratory tract infection) or evidence of viral hepatitis exposure on screening unless only HbsAb+ and HBV