Intra-osseous Donor Umbilical Cord Blood and Mesenchymal Stromal Cell Co-transplant in Treating Patients with Hematologic Malignancies

Inclusion Criteria

• Acute myelogenous leukemia (AML): high-risk AML including: * Antecedent hematological disease (e.g., myelodysplasia [MDS]) * Treatment-related leukemia * Complete remission (first complete remission [CR1]) with poor-risk cytogenetics or molecular markers (e.g. fms-related tyrosine kinase 3 [Flt 3] mutation, 11q23, del 5, del 7, complex cytogenetics) * Second complete remission (CR2) or third complete remission (CR3) * Induction failure or 1st relapse with either ** =< 10% blasts in the marrow or ** =< 5% blasts in the peripheral blood
• Acute lymphoblastic leukemia (ALL) * High-risk CR1 including: * Poor-risk cytogenetics (e.g., Philadelphia chromosome t(9;22) or 11q23 rearrangements) * Presence of minimal disease by flow cytometry after 2 or more cycles of chemotherapy * No complete remission (CR) within 4 weeks of initial treatment * Induction failure * CR2 or CR3 with either ** =< 10% blasts in the marrow or ** =< 5% blasts in the peripheral blood
• Myelodysplastic syndromes (MDS), intermediate-1 (INT-1), intermediate-2 (INT-2) or high Revised International Prognostic Scoring System (IPSS-R) score that has failed at least 1 first line therapy; also included are overlap syndromes of MDS and myeloproliferative neoplasms
• Myelofibrosis (MF): * Intermediate-2 or high risk by Dynamic International Prognostic Scoring System (DIPSS)-plus OR * Monosomal karyotype OR * Presence of inv(3)/i(17q) abnormalities OR * Other unfavorable karyotype OR leukocytes >= 40 x 10^9/L AND * Circulating blasts =< 9%
• Relapsed or refractory lymphoid malignancies (including non-Hodgkin lymphoma, Hodgkin lymphoma and chronic lymphocytic leukemia) meeting the following criteria: * Disease status: stable disease, partial remission or 2nd and 3rd complete remission
• Chronic myelogenous leukemia (CML) in second chronic phase after accelerated or blast crisis; blast crisis defined as: * Blast count >= 20% in the peripheral blood or bone marrow * Large foci of blasts on bone marrow * Presence of extra-medullary blastic infiltrate (myeloid sarcoma or chloroma)
• Myeloproliferative Neoplasms (MPN) with high risk of transformation to leukemia: * Blast count >= 5% in the peripheral blood or bone marrow * Large foci of blasts on bone marrow * Gain of genetic mutations over the course of the disease including, but not limited to CALR, TET2, ASXL1, TP53, IDH 1/2 and additional chromosomal abnormalities * Patients who have failed one or more cytoreductive therapies
• Recipients of prior autologous or allogeneic transplant are eligible, as long as at least 3 months have passed since the transplant, and the patient fulfills other eligibility criteria
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Candidates for reduced intensity conditioning regimens
• Patients who do not have human leukocyte antigen (HLA)-matched (defined as matched in HLA A, B, C, and DRB1) related or unrelated donors, those who elect to undergo UCB even if they have a match-related donor (MRD) or match unrelated donor (MUD), or patients who require a UCB either for emergency indications such as primary graft failure
• Cord blood units available through National Marrow Donor Program (NMDP) with the following minimal criteria; * HLA Match: 4/6 or better match (HLA A, B, DRB1) * Cell dose: minimum of 2 x 10^7 total number of nucleated cells (TNC)/kg pre thaw
• Concurrent therapy for extramedullary leukemia or central nervous system (CNS) lymphoma: concurrent therapy or prophylaxis for testicular leukemia, CNS leukemia, and CNS lymphoma including standard intrathecal chemotherapy and/or radiation therapy will be allowed as clinically indicated; such treatment may continue until the planned course is completed; subjects must be in CNS remission at the time of protocol enrollment if there is a history of CNS involvement
• Subjects must have a back-up umbilical cord on the registry in addition to the umbilical cord being used in this study
• Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Creatinine clearance < 30 ml/min
• Bilirubin >= 2 x institutional upper limit of normal * Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) >= 2 x institutional upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) >= 2 x institutional upper limit of normal
• Corrected diffusing capacity of the lung for carbon monoxide (DLCOcorr) < 40% normal
• Left ventricular ejection fraction < 35%
• Patients with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breastfeeding women are excluded from this study because chemotherapy involved with RIC have the significant potential for teratogenic or abortifacient effects