In this Phase I study, the study team will evaluate the safety of Valproic Acid (VPA) expanded cord blood stem cells defined by the lack of serious infusion reactions or graft failure in patients with hematological malignancies undergoing umbilical cord blood transplantation. Moreover, the study team will also evaluate time to neutrophil and platelet engraftment as well as transplant related outcomes such as graft versus host disease (GVHD), treatment related mortality (TRM), and overall survival (OS).

This is a phase I trial for safety of VPA expanded cord blood stem cells in patients with hematological malignancies undergoing allogeneic stem cell transplantation. The primary endpoint of the study is safety as defined by the incidence of infusion reactions and graft failure, lack of neutrophil engraftment by day +42. The trial will consist of two cohorts. First cohort of 5-7 patients, will undergo double umbilical cord blood (UCB) transplantation. One UCB unit will undergo CD34 selection followed VPA based expansion. CD34 negative portion of that unit will be cryopreserved to be infused later following infusion of the expanded portion. Infusion of the second unmanipulated UCB will follow it. Preparative regimen is Fludarabine 150 mg/m2/Cytoxan 50 mg/m2/Thiotepa 10 mg/m2/TBI 400cGy.

Following successful engraftment in the first cohort, second cohort (10 patients) will only receive single manipulated unit.

Otherwise, patients will receive standard allogeneic stem cell transplantation care.

Inclusion Criteria:

Disease criteria:

Patients with the following hematological malignancies:

• Acute Myeloid Leukemia (AML) in complete remission (CR)
• Acute Lymphoblastic Leukemia (ALL) in complete remission (CR)
• Myelodysplastic Syndrome (MDS) requiring intensive chemotherapy
• Non-Hodgkin lymphoma in complete or partial remission
• Hodgkin lymphoma in complete or partial remission

Age Criteria:

- 18 years up to 65 years.

Organ Function and Performance Status Criteria:

- Performance status score: Karnofsky Score ≥60

Adequate major organ function defined as:

• Left ventricular ejection fraction ≥40%
• Pulmonary function test demonstrating DLCO ≥50% predicted and corrected for hemoglobin
• Serum creatinine ≤ 2 mg/dL
• Transaminases ≤ 3x ULN
• Bilirubin ≤3x ULN except for in case of Gilbert's syndrome or ongoing hemolysis
• Ability to understand and the willingness to sign a written informed consent document

Donor availability:

-Lack of suitable HLA matched related or unrelated donor available within 30 days or less if BMT is urgent in the opinion of the transplant physician.

Exclusion Criteria:

• Progressive, persistent disease or active malignancy
• Greater than 10% blasts on bone marrow biopsy in patients with MDS
• Chemotherapy naïve
• History of myelofibrosis
• Presence of Bone Marrow Fibrosis grade 2/3
• Presence of donor specific anti-HLA antibodies against available UCB units at A, B, C or DR loci, with a mean fluorescence intensity (MFI)>1000
• History of prior allogeneic stem cell transplantation
• Uncontrolled viral, bacterial or fungal infection
• History of HIV infection
• Presence of active CNS disease at the time of transplantation
• Pregnant or breastfeeding female
• Inability or unwillingness to use effective birth control.