Sequential treatment with FLAG-IDA/treosulfan conditioning regimen for patients with active acute myeloid leukemia
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ORIGINAL ARTICLE
Sequential treatment with FLAG-IDA/treosulfan conditioning regimen for patients with active acute myeloid leukemia Liat Shargian-Alon 1,2 & Ofir Wolach 1,2 & Uri Rozovski 1,2 & Dafna Yahav 2,3 & Michal Sela-Navon 1 & Mazal Rubinstein 1 & Nino Oniashvilli 2,4 & Oren Pasvolsky 1,2 & Pia Raanani 1,2 & Moshe Yeshurun 1,2 Received: 6 May 2020 / Accepted: 24 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Sequential protocols combining salvage chemotherapy with reduced intensity conditioning (RIC) and allogeneic hematopoietic cell transplantation (alloHCT) for high-risk acute myeloid leukemia (AML) have been studied more than a decade. Purpose of this retrospective analysis was to evaluate the anti-leukemic efficacy and toxicity of FLAG-IDA protocol (fludarabine, cytarabine, and idarubicin) followed by treosulfan-based conditioning for patients with active AML. From January 2014 to November 2019, a total of 29 active AML patients [median age, 64 years (range, 23–73)] were treated. All patients completed protocol regimen and were transplanted. Five patients (17%) had grade 3–4 toxicities; therefore, treosulfan was substituted with total body irradiation (TBI) non-myeloablative conditioning. Six (20%) patients died within 30 post-transplant days, all from infectious complications. Out of 23 evaluable patients on day 30, 22 (96%) achieved complete hematologic remission with full donor chimerism. Non-relapse mortality (NRM) rates at 1 and 3 years were 22% and 49%, respectively. Median overall survival (OS) was 12 (95% CI, 4–20) months. OS and disease-free survival were 50% and 46% at 1 year and 28% and 17% at 2 years, respectively. Age, gender, disease burden, number of previous lines, and comorbidity score did not predict survival. Sequential strategy combining FLAG-IDA and treosulfan may offer a salvage option for few selected patients with active AML; however, high NRM presents a major obstacle to treatment success. Future efforts should focus on reducing NRM by moderating regimen intensity and by better selection of patients. Keywords Relapsed and refractory AML . Salvage . Sequential . Allogeneic hematopoietic cell transplantation
Introduction Relapsed/refractory acute myeloid leukemia (R/R AML) is a difficult to treat clinical scenario. Overall outcome after conventional chemotherapy alone is dismal and allogeneic hematopoietic cell transplantation (alloHCT) remains the only curative approach to date [1]. Ideally, patients with AML should Liat Shargian-Alon and Ofir Wolach contributed equally to this work. * Liat Shargian-Alon [email protected] 1
Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, 49100 Petah-Tikva, Israel
2
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
3
Infectious Disease Unit, Rabin Medical Center, Petah-Tikva, Israel
4
The Raphael Recanati Genetic Institute, Rabin Medical Center, Petah-Tikva, Israel
enter alloHCT in complete remission (CR) since active disease at alloHCT is asso
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