2 amongst patients undergoing autologous transplant for multiple myeloma : a multicentre UK study

Background Intravenous (iv) Busulfan plus fludarabine (BF) is a widely used conditioning regimen for matched sibling (MSD) and unrelated donor (URD) transplant (SCT) in AML.Thiotepa, busulfan and fludarabine (TBF) regimen was initially developed for cord blood and subsequently employed in haplo-SCT;however, there is limited evidence about its value in MSD and URD SCT in AML. Patients and methods We included adult AML patients (pts) who had received TBF or BF as conditioning regimen for MSD or URD SCT in CR1 between 2007 and 2015,reported to the EBMT.Pts who received oral busulfan,T-depleted grafts,or transplant from 8/10 or inferior HLA-matched donor were excluded.Myeloablative conditioning regimen (MAC) was defined by iv Busulfan dose>=9.6 mg/kg (TBF-MAC and BF-MAC),while reduced-intensity conditioning (RIC) by iv Busulfan dose of 6.4 mg/kg (TBF-RIC and BF-RIC).A total of 2910 pts met the inclusion criteria (212 TBF and 2698 BF). 147 pts received TBF-MAC and 65 TBF-RIC,while 1459 received BF-MAC and 1239 BF-RIC regimen, respectively. Fifty-seven percent of the pts were transplanted from MSD,34% from 10/10 URD and 9% from 9/10 URD, respectively. Results As compared to BF-MAC,TBF-MAC group included significantly younger pts (45 vs 50 years),which were transplanted more recently (2014 vs 2013),received more frequently URD transplant (49% vs 35%) from a male donor (69% vs 59%) and BM as stem cell source (34% vs 17%).Engraftment rate was 98% following both regimens.The 2-year NRM was significantly higher after TBF-MAC compared to BF-MAC (27% vs 16%, p=0.006),respectively.Incidence of grade II-IV aGVHD was 25% vs 24% (p=0.8),respectively.The 2-year cumulative incidence of cGVHD was similar following TBF-MAC (35%) compared to BF-MAC (40%, p=0.5).The 2year RI was significantly lower in TBF-MAC (14%) compared to BF-MAC (27%, p=0.002), while LFS and OS were 59% vs 57% (p=0.5) and 62% vs 61% (p=0.9) in TBF-MAC vs BF-MAC,respectively.The 2-year refined GVHDfree,relapse-free survival (GRFS) was 52% in TBF-MAC and 41% in BF-MAC (p=0.2).Multivariate analysis confirmed significantly higher NRM (HR 2.7, p<10 -4 ) and lower RI (HR 0.47, p=0.005) for TBF-MAC,thus leading to similar LFS (p=0.6) and OS (p=0.3) as compared to BF-MAC.A propensity score (PS)-matched pair analysis conducted on 138 TBF-MAC vs 262 BF-MAC pts confirmed those results.Among pts who received a RIC