Panobinostat Maintenance After HSCT fo High-risk AML and MDS

Inclusion Criteria

• •Adult patients (18-70 years of age)
• •AML (except acute promyelocytic leukemia with PML-RARA and AML with BCR-ABL1) according to WHO 2016 classification with high-risk features defined as one or more of the following criteria:
• •* refractory to or relapsed after at least one cycle of standard chemotherapy
• •* \> 10% bone marrow blasts at day 14-21 of the first induction cycle
• •* adverse risk according to ELN 2017 risk stratification by genetics (Appendix 2) regardless of stage
• •* secondary to MDS or radio-/chemotherapy
• •* MRD positive before HSCT based on flow cytometry or PCR
• •or
• •MDS with excess blasts (MDS-EB) according to the WHO 2016 classification, or high-risk or very high-risk according to IPSS-R
• •and
• •First allogeneic HSCT scheduled within the next 4-6 weeks using one of the following donors, conditioning regimens and strategies for GvHD prophylaxis:
• •1. Matched sibling or matched unrelated donor (i.e. 10/10 or 9/10 HLA-matched) or haploidentical family donor
• •2. Conditioning regimens:
• •1. Reduced-intensity conditioning:
• •a. Fludarabine/Melphalan b. Fludarabine/Busulfan2 (FB2) (2) Myeloablative conditioning:
• •1. Fludarabine/Busulfan4 (FB4)
• •2. Busulfan/Cyclophosphamide (BU/CY)
• •3. Fludarabine/TBI 8 Gy
• •4. Cyclophosphamide/TBI 12 Gy (3) Fludarabine/Cyclophosphamide/TBI 2 Gy in combination with post-Tx cyclophosphamide (TP-CY) only (4) Thiotepa/Busulfan/Fludarabine (TBF) in the context of an haploidentical HSCT only (5) In case of active disease at HSCT, salvage chemotherapy prior to conditioning is permitted
• •c. Strategies for GvHD prophylaxis:
• •1. HLA-matched donors:
• •a. CSA + MMF +/- ATG b. CSA + MTX +/- ATG c. PT-CY + CSA
• •2. Haploidentical donors:
• •d. PT-CY + CSA + MMF
• •\- No history of significant cardiac disease and absence of active symptoms, otherwise documented left ventricular EF ≥ 40%
• •\- Written informed consent for registration