Allo-SCT for AML and MDS with treosulfan compared with BU-based regimens: reduced toxicity vs reduced intensity.
Allo-SCT with reduced-intensity conditioning (RIC) results in lower non-relapse mortality (NRM), but higher relapse rate than myeloablative conditioning (MAC) in AML/myelodysplastic syndromes (MDS). Novel regimens with intensive anti-leukemic activity, but with limited toxicity will be of benefit. In all, 85 patients with AML/MDS, not eligible for MAC, were given fludarabine-treosulfan conditioning (FT). Outcomes were compared with those in patients given fludarabine-BU RIC (FB2, n=106) or reduced-toxicity (RTC) conditioning (FB4, fludarabine and myeloablative BU dose, n=85). The 5-year NRM was 29%, 20% and 18% after FT, FB2 and FB4, respectively (P=NS). Multivariate analysis (MVA) identified comorbidity score (HCT-CI) >2 and advanced disease as adverse factors with no independent impact of regimen. The 5-year relapse rate was 36%, 47% and 40%, respectively (P=0.17). MVA identified advanced disease as the major adverse factor, while FT had significantly lower relapse rate (hazard ratio 0.6, P=0.03). The 5-year survival (OS) was 37% with advanced disease. HCT-CI >2 and age ≥ 50 were found as adverse factors. The 5-year OS was 46%, 44% and 50% after FT, FB2 and FB4 in early-intermediate-stage disease (P=NS) and 33%, 9% and 28% in advanced disease, respectively (P=0.02). FT is an RTC regimen with intensive anti-leukemia effect in MAC non-eligible patients.
Department of Bone Marrow Transplantation, The Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel. ashimoni@sheba.health.gov.il
A
A
Shimoni
N
N
Shem-Tov
Y
Y
Volchek
I
I
Danylesko
R
R
Yerushalmi
A
A
Nagler
D000328:Adult; D000368:Aged; D002066:Busulfan / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D015996:Survival Rate; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D019653:Myeloablative Agonists; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine