Thiotepa, Fludarabine Phosphate, and Melphalan Hydrochloride in Treating Patients with Blood Cancer Undergoing Donor Stem Cell Transplant

Inclusion Criteria

• Patients with the following hematologic malignancies: * Acute myelogenous leukemia (AML): High-risk AML including: ** Antecedent hematological disease (e.g., myelodysplasia [MDS]) ** Treatment-related leukemia ** Complete remission (CR1) with poor or intermediate-risk cytogenetics or molecular markers (e.g. Flt 3 mutation, 11q23, del 5, del 7, complex cytogenetics) ** CR2 or CR3 ** Induction failure or 1st relapse with =< 10% blasts in the marrow * 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 CR within 4 weeks of initial treatment ** Induction failure with =< 10% blasts in the marrow ** CR2 or CR3 * Myelodysplastic syndromes (MDS), intermediate, high or very high risk by the revised international prognostic scoring system (IPSS-R) or treatment related MDS * Mixed Phenotypic Leukemia / Biphenotypic Leukemia in CR * Chronic myelogenous leukemia (CML) in second chronic phase after accelerated or blast crisis * Myelofibrosis (MF): ** Intermediate-1, 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% * Chronic myelomonocytic leukemia * Relapsed or refractory lymphoid malignancies (including non-Hodgkin lymphoma, Hodgkin lymphoma) meeting the following criteria: ** Disease status: Stable disease, partial remission or complete remission OR ** Have relapsed after autologous transplant or who have failed to collect for an autologous transplant
• Age > 1 years, < 65yrs
• Karnofsky performance status (KPS) >= 80
• Patients without a matched related donor
• Patient with either one or both: * A related haplo-identical donor * Two 4/8 HLA or better high resolution matched umbilical cord blood (UCB) grafts with a cell dose of 1.5 x 10^7 total nucleated cell (TNC)/kg each and 1 x 10^5 CD34+ cells/ kg each
• 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. Maintenance therapy after transplant is allowed
• Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Creatinine clearance < 50 ml/min
• Bilirubin >= 2 X institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) >= 3 X institutional upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) >= 3 X institutional upper limit of normal
• Pulmonary function: Carbon monoxide diffusing capability (DLCOc) < 60% normal
• Cardiac: left ventricular ejection fraction < 50%
• KPS < 80
• 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 reduced intensity conditioning (RIC) have the significant potential for teratogenic or abortifacient effects
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data
• Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds
• Presence of donor-specific antibodies against chosen graft source