Long-term outcome after a treosulfan-based conditioning regimen for patients with acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
BACKGROUND
Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for patients with acute myeloid leukemia (AML). However, post-HCT relapse and regimen-related toxicity remain significant barriers to long-term survival. In recent years, new conditioning regimens have been explored to improve transplantation outcomes in patients with AML. Treosulfan combines a potent immunosuppressive and antileukemic effect with a low toxicity profile.


METHODS
To investigate the role of treosulfan-based conditioning, the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party performed a registry analysis of 520 adult patients with AML who received treosulfan-based conditioning and underwent HCT between 2000 and 2012, including 225 patients in first complete remission, 107 in second or later complete remission, and 188 with active/advanced disease 188 (88 with primary refractory disease). The median patient age was 57 years (range, 20-73 years). Donors were human leukocyte antigen-identical siblings (n = 187), unrelated donors (n = 235), or mismatched related donors (n = 98). Conditioning regimens included treosulfan (42 g/m2[n = 396], 36 g/m2[n = 109], or 30 g/ m2[n = 15]) with fludarabine or alkylating agents followed by infusion of hematopoietic stem cells (bone marrow, n = 52; peripheral blood, n = 468).


RESULTS
At a median follow-up of 61 months, the 5-year overall survival, leukemia-free survival, relapse incidence, and nonrelapse mortality rates were 38%, 33%, 42%, and 25%, respectively. The incidence of grade II-IV acute and chronic graft-versus-host disease was 24% (grade III-V, 11%) and 38%, respectively. Only 11 patients (2%) developed veno-occlusive disease, with two deaths (0.4%) from veno-occlusive disease.


CONCLUSIONS
Treosulfan-based conditioning regimens provide an acceptable long-term survival with favorable nonrelapse mortality and a very low risk of veno-occlusive disease. Further studies are needed to optimize the treosulfan-based conditioning regimen for patients with AML. Cancer 2017;123:2671-79. © 2017 American Cancer Society.
Acute Leukemia Working Party, European Society for Blood and Marrow Transplantation Paris Study Office/European Center for Biostatistical and Epidemiological Evaluation in Hematopoietic Cell Therapy (CEREST-TC), Paris, France.|Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Arnon
A
Nagler
Acute Leukemia Working Party, European Society for Blood and Marrow Transplantation Paris Study Office/European Center for Biostatistical and Epidemiological Evaluation in Hematopoietic Cell Therapy (CEREST-TC), Paris, France.|Department of Hematology, St. Antoine Hospital, Paris, France.|INSERM UMR 938, Paris, France.|Pierre and Marie Curie University, Paris, France.
Myriam
M
Labopin
Department of Bone Marrow Transplantation, University Hospital, Essen, Germany.
Dietrich
D
Beelen
Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milano, Italy.
Fabio
F
Ciceri
Stem Cell Transplantation Unit, Comprehensive Cancer Center, Helsinki University Central Hospital, Helsinki, Finland.
Liisa
L
Volin
Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Avichai
A
Shimoni
Department of Cellular Biotechnology and Hematology, University La Sapienza, Rome, Italy.
Roberto
R
Foá
CHU Bordeaux, Hôpital Haut-Leveque, Pessac, France.
Noel
N
Milpied
Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milano, Italy.
Jacopo
J
Peccatori
Acute Leukemia Working Party, European Society for Blood and Marrow Transplantation Paris Study Office/European Center for Biostatistical and Epidemiological Evaluation in Hematopoietic Cell Therapy (CEREST-TC), Paris, France.
Emmanuelle
E
Polge
Acute Leukemia Working Party, European Society for Blood and Marrow Transplantation Paris Study Office/European Center for Biostatistical and Epidemiological Evaluation in Hematopoietic Cell Therapy (CEREST-TC), Paris, France.
Audrey
A
Mailhol
Acute Leukemia Working Party, European Society for Blood and Marrow Transplantation Paris Study Office/European Center for Biostatistical and Epidemiological Evaluation in Hematopoietic Cell Therapy (CEREST-TC), Paris, France.|Department of Hematology, St. Antoine Hospital, Paris, France.|INSERM UMR 938, Paris, France.|Pierre and Marie Curie University, Paris, France.
Mohamad
M
Mohty
Acute Leukemia Working Party, European Society for Blood and Marrow Transplantation Paris Study Office/European Center for Biostatistical and Epidemiological Evaluation in Hematopoietic Cell Therapy (CEREST-TC), Paris, France.|Long-Term Transplantation Clinic, Vanderbilt University Medical Center, Nashville, Tennessee.
Bipin N
http://orcid.org/0000-0002-3304-9965
BN
Savani
D000328:Adult; D000368:Aged; D000477:Alkylating Agents / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D002066:Busulfan / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002423:Cause of Death; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D012042:Registries; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D055815:Young Adult
D000477:Alkylating Agents; D018906:Antineoplastic Agents, Alkylating; D019653:Myeloablative Agonists; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
acute myeloid leukemia; allogeneic stem cell transplantation; conditioning regimen; graft-versus leukemia effect; toxicity; treosulfan