Treosulfan Based Conditioning Prior To Allogeneic Stem Cell Transplantation (HSCT) For Acute Myelogenous Leukemia (AML): A Retrospective Analysis From The ALWP Of The EBMT

Allogeneic Hematopoietic SCT (HSCT) is a curative treatment for high risk AML. However, search continues for novel conditioning regimens that will reduce SCT-related toxicity while retaining maximal anti-leukemia effect. Treosulfan (L-threitol-1, 4-bis-methanesulfonate; dihydroxybusulfan) was shown in preclinical studies to have a myeloablative effect on committed and non-committed stem cells. In addition, it has potent immunosuppressive characteristics, which makes it an attractive candidate for use in conditioning regimens before HSCT. We therefore preformed a retrospective analysis of the data for HSCT with Treosulfan based conditioning using the ALWP data set. We analyzed 795 HSCT in which Treosulfan was used in the pre-transplantation conditioning in adult patients with AML that were transplanted between Jan 2000 and Dec 2011. Out of the 795 AML patients 375 were transplanted in CR1, 197 in CR2 and 223 with active disease. 258 (32%) were transplanted from HLA matched sibling donors, 465 (58%) from unrelated donor and 72 (9%) from family mismatch donor. Mobilized peripheral blood stem cells (PBSC) were used as the graft source for 700 (89%), and bone marrow (BM) for 95 (12%) of the transplants. Conditioning was myeloablative (MAC) in 505 (64%), and reduced toxicity regiments (RTC) in 290 (36%) of the HSCT. Most frequently the Treosulfan based conditioning was combined with Fludarabine (Flu/Treo) and was used in 67% of the MAC and 86% of RTC. In 96 transplants Treosulfan was combined with Cyclophosphamid (Cy) and Etoposide (VP16). Other combinations included Melphalan (n=56), ARA-C (n=19) and Clofarabin (n=7). The median follow-up was 14 mo (1-116). Engraftment was achieved in 96% of the HSCT with no difference between MAC and RTC 95% and 97%, respectively. NRM were 17±4%, 21±2% and 33±3% for patients in CR¹, CR² and advance disease, respectively. Acute GVHD ≥ II occurred in 21% of the HSCT and was the same for MAC and RTC HSCT, while 2 year incidence of chronic GVHD (2y) was seen in 43±2% of HSCT (MAC-45%, RTC-38%). Incidences of relapse were 31±2%, 36±4% and 43±4% for patients transplanted in CR¹, CR² and advance disease, respectively. 2y OS and DFS were 61±3% and 51±3% for patients in CR¹, 53±4% and 43±4% in patients with CR² and 32±4% and 24±3% in patients with advanced disease. LFS was similar for MAC and RTC HSCT 60±5% and 50±8% for patients transplanted in CR¹ from sibling donors while 43±6% and 50±6% for those transplanted from unrelated donors, respectively. Relapse rate were also similar 30±4% and 39±8% vs. 35±6% and 28±6% for transplants from siblings and unrelated donors, respectively. While NRM was 9±3% and 11±5% vs. 22±4% and 21±5% for HSCT from siblings vs. unrelated with MAC vs. RTC, respectively. In conclusion: Treosulfan mostly in combination with Fludarabin for conditioning prior to HSCT is associated with good engraftment, acceptable rates of NRM, GVHD, OS and LFS for patients in both CR¹ and CR². Further studies analyzing the use of Treosulfan in pre-HSCT conditioning regiments are in need.