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Title: Adult patients with Ph+ ALL benefit from conditioning regimen of medium‐dose VP16 plus CY/TBI
Authors: Morita-Fujita, Mari
Arai, Yasuyuki  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-9662-5093 (unconfirmed)
Kondo, Tadakazu
Harada, Kaito
Uchida, Naoyuki
Toya, Takashi
Ozawa, Yukiyasu
Fukuda, Takahiro
Ota, Shuichi
Onizuka, Makoto
Kanda, Yoshinobu
Maruyama, Yumiko
Takada, Satoru
Kawakita, Toshiro
Ara, Takahide
Ichinohe, Tatsuo
Kimura, Takafumi
Atsuta, Yoshiko
Kako, Shinichi
Author's alias: 森田, 真梨
新井, 康之
近藤, 忠一
Keywords: acute lymphoblastic leukemia
Philadelphia chromosome
VP16/CY/TBI
Issue Date: Dec-2022
Publisher: Wiley
Journal title: Hematological Oncology
Volume: 40
Issue: 5
Start page: 1041
End page: 1055
Abstract: The medium-dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi-center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post-transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome-positive (Ph+) and -negative (Ph−) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph− ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression-free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55–0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37–0.90; p = 0.02) without the increase of non-relapse mortality (NRM). By contrast, in patients with Ph− ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph− ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well-tolerated regimen in comparison with CY/TBI in patients with myeloablative allo-HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL.
Rights: © 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
URI: http://hdl.handle.net/2433/279368
DOI(Published Version): 10.1002/hon.3046
PubMed ID: 35790020
Appears in Collections:Journal Articles

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