TY - JOUR
T1 - Improved Outcomes of Haploidentical Hematopoietic Cell Transplantation with Total Body Irradiation-Based Myeloablative Conditioning in Acute Lymphoblastic Leukemia
AU - Dholaria, Bhagirathbhai
AU - Labopin, Myriam
AU - Angelucci, Emanuele
AU - Tischer, Johanna
AU - Arat, Mutlu
AU - Ciceri, Fabio
AU - Gülbas, Zafer
AU - Ozdogu, Hakan
AU - Sica, Simona
AU - Diez-Martin, Jose Luis
AU - Koc, Yener
AU - Pavlu, Jiri
AU - Socié, Gerard
AU - Giebel, Sebastian
AU - Savani, Bipin N.
AU - Nagler, Arnon
AU - Mohty, Mohamad
N1 - Funding Information:
The authors thank the centers of the EBMT and national registries for contributing patient information and performing data collection. Supporting information is available on the EBMT website (www.ebmt.org). The reporting institutions included in this study are listed in the Supplementary Material. Financial disclosure: No relevant financial disclosures from authors. Conflict of interest statement: There are no conflicts of interest to report. Authorship statement: B.D. B.N.S. A.N. M.M. and M.L. contributed to the conception and design of the study; M.L. analyzed the data; and B.D. A.N. M.L. M.M. B.N.S. wrote the manuscript. All authors critically reviewed the manuscript and approved the final version. Financial disclosure: See Acknowledgments on page XXX.
Publisher Copyright:
© 2020 The American Society for Transplantation and Cellular Therapy
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021
Y1 - 2021
N2 - The optimal myeloablative conditioning (MAC) for patients undergoing haploidentical hematopoietic cell transplantation (haplo-HCT) is unknown. We studied the outcomes of total body irradiation (TBI)-based versus chemotherapy (CT)-based MAC regimens in patients with acute lymphoblastic leukemia (ALL). The study included 427 patients who underwent first haplo-HCT with post-transplantation cyclophosphamide (PTCy), following TBI-based (n = 188; 44%) or CT-based (n = 239; 56%) MAC. The median patient age was 32 years. Fludarabine-TBI (72%) and thiotepa-busulfan-fludarabine (65%) were the most frequently used TBI- and CT-based regimens, respectively. In the TBI and CT cohorts, 2-year leukemia-free survival (LFS) was 45% versus 37% (P = .05), overall survival (OS) was 51% versus 47% (P = .18), relapse incidence (RI) was 34% versus 32% (P = .44), and nonrelapse mortality (NRM) was 21% versus 31% (P < .01). In the multivariate analysis, TBI was associated with lower NRM (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.33 to 0.86; P = .01), better LFS (HR, 0.71; 95% CI, 0.52 to 0.98; P =.04), and increased risk for grade II-IV acute graft-versus-host disease (GVHD) (HR, 1.59; 95% CI, 1.08 to 2.34; P = .02) compared with CT-based MAC. The type of conditioning regimen did not impact RI, chronic GVHD, OS, or GVHD-free, relapse-free survival after adjusting for transplantation-related variables. TBI-based MAC was associated with lower NRM and better LFS compared with CT-based MAC in patients with ALL after haplo-HCT/PTCy.
AB - The optimal myeloablative conditioning (MAC) for patients undergoing haploidentical hematopoietic cell transplantation (haplo-HCT) is unknown. We studied the outcomes of total body irradiation (TBI)-based versus chemotherapy (CT)-based MAC regimens in patients with acute lymphoblastic leukemia (ALL). The study included 427 patients who underwent first haplo-HCT with post-transplantation cyclophosphamide (PTCy), following TBI-based (n = 188; 44%) or CT-based (n = 239; 56%) MAC. The median patient age was 32 years. Fludarabine-TBI (72%) and thiotepa-busulfan-fludarabine (65%) were the most frequently used TBI- and CT-based regimens, respectively. In the TBI and CT cohorts, 2-year leukemia-free survival (LFS) was 45% versus 37% (P = .05), overall survival (OS) was 51% versus 47% (P = .18), relapse incidence (RI) was 34% versus 32% (P = .44), and nonrelapse mortality (NRM) was 21% versus 31% (P < .01). In the multivariate analysis, TBI was associated with lower NRM (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.33 to 0.86; P = .01), better LFS (HR, 0.71; 95% CI, 0.52 to 0.98; P =.04), and increased risk for grade II-IV acute graft-versus-host disease (GVHD) (HR, 1.59; 95% CI, 1.08 to 2.34; P = .02) compared with CT-based MAC. The type of conditioning regimen did not impact RI, chronic GVHD, OS, or GVHD-free, relapse-free survival after adjusting for transplantation-related variables. TBI-based MAC was associated with lower NRM and better LFS compared with CT-based MAC in patients with ALL after haplo-HCT/PTCy.
KW - Acute lymphoblastic leukemia
KW - Allogeneic hematopoietic cell transplantation
KW - Antineoplastic combined chemotherapy protocols
KW - Conditioning
KW - Disease relapse
KW - Graft-versus-host disease
KW - Haploidentical
KW - Lymphoma
KW - Myeloablative
KW - Total body irradiation
KW - Toxicity
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U2 - 10.1016/j.jtct.2020.10.008
DO - 10.1016/j.jtct.2020.10.008
M3 - Article
AN - SCOPUS:85101096184
VL - 27
SP - 171.e1-171.e8
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
SN - 2666-6375
IS - 2
ER -