Thiotepa Plus Fludarabine+ Melphalan as the Preparative Regime for Alternative Donor Transplantation

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-risk cytogenetics or molecular markers (e.g. 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 ≤ 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)
• Mixed Phenotypic Leukemia / Biphenotypic Leukemiain 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 × 10(9) /L and
• Circulating blasts ≤ 9%
• Chronic Myelomonocytic Leukemia
• 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. OR
• Have relapsed after autologous transplant or who have failed to collect for an autologous transplant.
• Age > 1 years, twice institutional upper limit of normal
• aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) ≥ three times institutional upper limit of normal
• Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) ≥ three times institutional upper limit of normal
• Pulmonary function: diffusing capacity of the lung for carbon monoxide corrected for hemoglobin (DLCOc) < 60% normal
• Cardiac: left ventricular ejection fraction < 50%
• Karnofsky Performance Statue (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.