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Fraccaroli, Alessia; Prevalsek, Dusan; Fritsch, Susanne; Haebe, Sarah; Buecklein, Veit; Schulz, Christoph; Hubmann, Max; Stemmler, Hans-Joachim; Ledderose, Georg; Hausmann, Andreas; Schmid, Christoph and Tischer, Johanna (2018): Sequential HLA-haploidentical transplantation utilizing post-transplantation cyclophosphamide for GvHD prophylaxis in high-risk and relapsed/refractory AML/MDS. In: American Journal of Hematology, Vol. 93, No. 12: pp. 1524-1531

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Abstract

This study evaluates the role of sequential therapy in HLA-haploidentical transplantation (haplo-HSCT) of high-risk, relapsed/refractory AML/MDS. We analyzed the course of 33 adults with active disease at time of transplantation (AML n = 30;MDS n = 3;median age 58 years, range: 32-71). Sequential therapy consisted of cytoreductive chemotherapy (FLAMSA n = 21;clofarabine n = 12) applied shortly prior to reduced intensity conditioning for T-cell-replete haplo-HSCT using post-transplantation cyclophosphamide as GvHD prophylaxis. No graft rejection was observed. Complete remission at day +30 was achieved in 97% of patients. CI of acute GvHD grade II-IV and chronic GvHD was 24% (no grade IV) and 23%, respectively. NRM at 1 and 3 years was 15%, each. Severe regimen-related toxicities (grade III-IV) were observed in 58%, predominantly involving the gastrointestinal tract (diarrhea 48%, mucositis 15%, transient elevation of transaminases 18%). Probability of relapse at 1 and 3 years was 28% and 35%. At a median follow-up of 36 months, the estimated 1- and 3-year overall survival was 56% and 48%. Disease-free survival was 49% and 40%, respectively. At 3 years, GvHD and relapse-free survival (GRFS) was 24% while chronic GvHD and relapse-free survival (CRFS) was 29%. Thus, our results indicate that sequential haplo-HSCT is an effective salvage treatment providing high anti-leukemic activity, favorable tolerance, and acceptable toxicity in patients suffering from advanced AML/MDS.

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