TY - JOUR
T1 - Intravenous Busulfan Compared with Treosulfan-Based Conditioning for Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia
T2 - A Study on Behalf of the Acute Leukemia Working Party of European Society for Blood and Marrow Transplantation
AU - Shimoni, Avichai
AU - Labopin, Myriam
AU - Savani, Bipin
AU - Hamladji, Rose Marie
AU - Beelen, Dietrich
AU - Mufti, Ghulam
AU - Socié, Gerard
AU - Delage, Jeremy
AU - Blaise, Didier
AU - Chevallier, Patrice
AU - Forcade, Edouard
AU - Deconinck, Eric
AU - Mohty, Mohamad
AU - Nagler, Arnon
N1 - Publisher Copyright:
© 2017 The American Society for Blood and Marrow Transplantation
PY - 2018/4
Y1 - 2018/4
N2 - Dose intensity of the conditioning regimen has significant impact on the outcomes after stem cell transplantation (SCT) for acute myeloid leukemia. Most studies have shown more relapse, less nonrelapse mortality (NRM), and similar overall survival after reduced-intensity and myeloablative conditioning. There are limited data on the dose equivalence and expected outcomes of treosulfan-based compared with busulfan-based conditioning. We compared SCT outcomes after fludarabine with either intravenous busulfan at a myeloablative dose (FB4, 12.8 mg/kg, n = 1265) or a reduced dose (FB2, 6.4 mg/kg, n = 1456) or treosulfan at 42 g/m 2 (FT14, n = 403) or 36 g/m 2 (FT12, n = 168). Median patient age was 48, 60, 57, and 60 years in the FB4, FB2, FT14, and FT12 groups, respectively (P <.0001). Two-year overall survival was 58%, 53%, 53%, and 51%, respectively (P =.25). Multivariate analysis identified advanced age, advanced disease status, and secondary leukemia to be associated with worse survival. Relapse rate was 30%, 35%, 34%, and 40%, respectively. Relapse was more common after FB2, advanced age and disease status, secondary leukemia, and sibling donors. NRM was 17%, 18%, 21%, and 16%, respectively. NRM was least common after FT12 and more common with advanced age and disease status and unrelated donors. Treosulfan-based regimens were associated with lower rates of graft-versus-host disease. There was no difference in any outcome among patients in first complete remission at transplantation. However, there was better survival with treosulfan-based conditioning in advanced leukemia. In conclusion, survival is determined mostly by disease biology and is similar after various regimens. Treosulfan-based conditioning is more similar to myeloablative than to reduced-intensity conditioning but can be administered safely in older patients, with lower rates of graft-versus-host disease and possibly better outcomes in patients with active leukemia.
AB - Dose intensity of the conditioning regimen has significant impact on the outcomes after stem cell transplantation (SCT) for acute myeloid leukemia. Most studies have shown more relapse, less nonrelapse mortality (NRM), and similar overall survival after reduced-intensity and myeloablative conditioning. There are limited data on the dose equivalence and expected outcomes of treosulfan-based compared with busulfan-based conditioning. We compared SCT outcomes after fludarabine with either intravenous busulfan at a myeloablative dose (FB4, 12.8 mg/kg, n = 1265) or a reduced dose (FB2, 6.4 mg/kg, n = 1456) or treosulfan at 42 g/m 2 (FT14, n = 403) or 36 g/m 2 (FT12, n = 168). Median patient age was 48, 60, 57, and 60 years in the FB4, FB2, FT14, and FT12 groups, respectively (P <.0001). Two-year overall survival was 58%, 53%, 53%, and 51%, respectively (P =.25). Multivariate analysis identified advanced age, advanced disease status, and secondary leukemia to be associated with worse survival. Relapse rate was 30%, 35%, 34%, and 40%, respectively. Relapse was more common after FB2, advanced age and disease status, secondary leukemia, and sibling donors. NRM was 17%, 18%, 21%, and 16%, respectively. NRM was least common after FT12 and more common with advanced age and disease status and unrelated donors. Treosulfan-based regimens were associated with lower rates of graft-versus-host disease. There was no difference in any outcome among patients in first complete remission at transplantation. However, there was better survival with treosulfan-based conditioning in advanced leukemia. In conclusion, survival is determined mostly by disease biology and is similar after various regimens. Treosulfan-based conditioning is more similar to myeloablative than to reduced-intensity conditioning but can be administered safely in older patients, with lower rates of graft-versus-host disease and possibly better outcomes in patients with active leukemia.
KW - Acute myeloid leukemia
KW - Busulfan
KW - Stem cell transplantation
KW - Treosulfan
UR - http://www.scopus.com/inward/record.url?scp=85041569338&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2017.12.776
DO - 10.1016/j.bbmt.2017.12.776
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C2 - 29247780
AN - SCOPUS:85041569338
SN - 1083-8791
VL - 24
SP - 751
EP - 757
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 4
ER -
