Pb2465: allogeneic hsct outcomes in six patients with therapy related myeloid neoplasms with a history of ovarian cancer treated with chemoterapy and parp inhibitors

Topic: 22. Stem cell transplantation - Clinical Background: PARP inhibitors (PARPi) transformed the management of ovarian cancer (OC), but they are associated with an increased risk of therapy-related myeloid neoplasms (t-MN) with poor outcome. Aims: To evaluate the role of intensive chemotherapy and allogeneic stem cell transplantation (allo-HSCT) in pts affected by unfavorable karyotypes t-MN associated to PARPi exposure. Methods: We investigated the impact of allo-HSCT in patients (pts) with t-MN after an OC history associated with a previous treatment including PARPi. We retrospectively reviewed clinical data of 6 consecutive pts undergoing allo-HSCT at our hospital between 2017 and 2020. Results: After a median PARPi exposure of 19 months (range 15-41) for an OC, 6 pts developed t-MN. 2 pts (32%) were BRCA mutated. Median age at hematological onset was 57 years (range 56-68). 4 pts (64%) showed a complete remission (CR) of OC. 3 pts developed a myelodysplastic syndrome/Acute Myeloid Leukemia (MDS/AML) with mutated Tp53, 1 pt showed MDS with mutated Tp53, 1 pt MDS/AML with myelodysplasia-related gene mutations with mutated RUNX1 and 1 pt AML with myelodysplasia-related cytogenetic abnormalities. All pts presented unfavorable karyotype and received intensive treatment which included cytarabine and an anthracycline (daunorubicin or idarubicin). After a median of 3 months (range 2-5) 5 pts (84%) reached a CR and 1 pt (16%) showed persistence of minimal residual disease by immunophenotyping. All pts underwent allo-HSCT, receiving myeloablative conditioning (treosulfan, fludarabine) and GVHD prophylaxis with post-HSCT cyclophosphamide, Mycophenolate Mofetil, Tacrolimus. 5 pts (84%) had haploidentical donor and 1 pt (16%) had matched sibling donor. Donor engraftment occurred in 5 (84%) pts with full donor chimerism achieved by day 29, reaching neutrophil and platelet graft with a median time of 17 (15-23) and 23 (10-42) days respectively. 2 pts (32%) developed steroid sensitive cutaneous acute GVHD grades II-III. 1 pt (16%) showed graft failure, underwent a second haploidentical allo-HSCT, receiving reduced intensity conditioning (fludarabine, cyclophosphamide, TBI 2Gy). The procedure was complicated by cutaneous refractory GVHD grade IV and she died 149 days after the second allo-HSCT. After a median time of 144 days (140-152) from allo-HSCT, 3 pts (48%) showed a Tp53 AML relapse (2 pts with BRCA mutated ovarian cancer) and died after a median time of 179 days (160-270). 1 pt (16%) developed post-transplant lymphoproliferative disorder and died after 90 days from the allo-HSCT. 1 (16%) pt was alive and in continuous CR after 50 months after allo-HSCT. She developed a progressive OC at 42 months after allo-HSCT, now receiving treatment. No other OC progression was detected. Summary/Conclusion: In our cohort 3 pts died of AML relapse, 2 pts died for transplant related mortality and 1 pt is alive in continuous CR of AML. The results obtained are in line with pts with AML with known high-risk features such as Tp53, RUNX1 and unfavorable karyotypes. The previous history of PARPi exposure in association with platinum-based chemotherapy in pts with OC did not clearly impact on allo-HSCT outcomes and should not be considered as a prohibitive factor for intensive treatment and allo-HSCT. Allo-HSCT not only might improves outcomes in this category of pts in which the hematological diagnosis drives the prognosis but can also give the chance to continue OC directed therapy that would otherwise be unfeasible. Keywords: Therapy-related AML, Allogeneic stem cell transplant, AML, Treatment