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. 2025 May 28;6(3):e70061.
doi: 10.1002/jha2.70061. eCollection 2025 Jun.

Efficacy of Total-Body Irradiation-based Intensified Myeloablative Regimens for Acute Leukemia-An International Collaborative Study

Yasuyuki Arai  1 , Ruta Brazauskas  2   3 , Naya He  3 , A Samer Al-Homsi  4 , Saurabh Chhabra  5 , Minoo Battiwalla  6 , Masamitsu Yanada  7 , Amir Steinberg  8 , Miguel Angel Diaz Perez  9 , Sanghee Hong  10 , Junya Kanda  1 , Asad Bashey  11 , Haydar A Frangoul  12   13 , Sherif M Badawy  14   15 , Leo F Verdonck  16 , Hillard M Lazarus  17 , Jean A Yared  18 , Hasan Hashem  19 , Akshay Sharma  20 , Mahmoud Aljurf  21 , Ajoy L Dias  22 , Muhammad Bilal Abid  23 , Baldeep Wirk  24 , César O Freytes  25 , Amer M Zeidan  26 , Usama Gergis  27 , Amer Beitinjaneh  28 , Medhat Askar  29 , Jeffrey J Pu  30 , Leslie E Lehmann  31 , Hemalatha G Rangarajan  32 , William A Wood  33 , Shahrukh Hashmi  34   35   36 , Shingo Yano  37 , Shinichi Kako  38 , Yukiyasu Ozawa  39 , Noriko Doki  40 , Yoshinobu Kanda  38 , Takahiro Fukuda  41 , Yuta Katayama  42 , Tatsuo Ichinohe  43 , Junji Tanaka  44 , Takanori Teshima  45 , Shinichiro Okamoto  46 , Yoshiko Atsuta  47   48 , Wael Saber  3
Affiliations

Efficacy of Total-Body Irradiation-based Intensified Myeloablative Regimens for Acute Leukemia-An International Collaborative Study

Yasuyuki Arai et al. EJHaem. .

Abstract

Background: In this study, we compared outcomes of intensified myeloablative conditioning regimens using large registry data from Japan (Japanese Society for Transplantation and Cellular Therapy) and the United States (Center for International Blood and Marrow Transplant Research).

Methods: Adult patients who underwent their first myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia in remission between 2010 and 2018 using conditioning regimens of cyclophosphamide plus total-body irradiation (CY/TBI), CY/TBI+cytarabine (AraC), or CY/TBI+etoposide (VP16) were included.

Results: The acute myeloid leukemia (AML) cohort (N = 480, 38.8%) indicated that overall survival (OS) was poorer in CY/TBI+AraC (hazard ratio [HR] 1.46, p < 0.001) and CY/TBI+VP16 (HR 1.39, p = 0.059) compared to CY/TBI. Relapse was not suppressed, while treatment-related mortality (TRM) was significantly higher (HR 1.78 and 1.74, p < 0.001 and 0.018, respectively). In the acute lymphoblastic leukemia (ALL) cohort (N = 3901, 61.2%), OS was comparable among these regimens. With intensified regimens, relapse was significantly suppressed in CY/TBI+VP16 (HR 0.74, p = 0.005), while TRM was higher (HR 1.21, p = 0.077). No interactions were observed regarding the country.

Conclusion: In AML adding AraC and VP16 to CY/TBI had an adverse effect on OS. Conversely, in ALL, adding VP16 or AraC to CY/TBI did not affect survival, but the addition of VP16 reduced the risk of relapse.

Clinical trial registration: The authors have confirmed clinical trial registration is not needed for this submission.

Keywords: acute leukemia; international collaborative study; myeloablative conditioning.

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Conflict of interest statement

Dr. Chhabra reports institutional research funding: Janssen, C4 Therapeutics, AbbVie, CARSgen, Takeda; honoraria for the advisory board: GSK, Sanofi, Janssen. Dr. Battiwalla reports compensation for research support from Novartis. Dr. Steinberg reports speaking for Jazz Pharmaceuticals Dr. Frangoul reports consulting for Vertex Pharmaceuticals and Editas Medicine. Dr. Lazarus reports consulting for Actinium Pharmaceuticals, Inc., Partner Therapeutics, Jazz Pharmaceuticals, Pluristem Therapeutics Inc., CSL Behring, Seattle Genetics; and promotional speaker for AstraZeneca; data safety monitoring for Bristol‐Myers Squibb and BioSight. Dr. Yared reports honoraria from participating in advisory board meetings with Incyte, Sanofi, Kadmon, and Omeros. Dr. Sharma reports consulting for Spotlight Therapeutics, Medexus Inc., Vertex Pharmaceuticals, and Sangamo Therapeutics; research funding from CRISPR Therapeutics. Clinical Trial site‐PI: CRISPR Therapeutics, Vertex Pharmaceuticals, Novartis Pharmaceuticals, Magenta Therapeutics, Beam Therapeutics, Honoraria: Vindico Medical Education. Dr. Dias reports the following disclaimer: This article was prepared by Dr Ajoy Dias in his personal capacity. The opinions expressed in this manuscript are the author's own and do not reflect the view of the National Institute of Health, the Department of Health and Human Services, or the United States government. Dr. Zeidan reports participation in advisory boards, consulted and/or received honoraria from AbbVie, Agios, Pfizer, Astellas, Astex, ALX Oncology, Amgen, Akeso pharma, BeiGene, BMS/Celgene, Boehringer‐Ingelheim, BioCryst, Chiesi, Daiichi Sankyo, Epizyme, Faron, Geron, Gilead, Genentech, Glycomimetics, Hikma, Ionis, Janssen, Kura, Keros, Karyopharm, Kyowa Kirin, Lava Therapeutics, Mendus, Notable, Novartis, Otsuka, Orum, Taiho, Takeda, Treadwell, Syndax, Sumitomo, STCube, Schrodinger, Servier, Syros, Vincerx, Regeneron, Rigel, and Zentalis. Dr. Rangarajan reports serving as the BMT Medical Monitor for NMDP (no financial reimbursements) and having served as an honorary consultant for Medexus. Dr. Hashmi reports compensation from advisory boards in Asia for GVHD and BMT drugs and reports giving talks on educational CME programs that are sponsored by pharma. Dr. Atsuta reports consulting for JCR Pharmaceuticals Co., Ltd, Kyowa Kirin Co., Ltd; honoraria from Meiji Seika Pharma Co, Ltd.; and lecturing for Otsuka Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd, Novartis Pharma KK, and AbbVie GK. Dr. Kako reports honoraria from Nippon Shinyaku Co., Ltd. Dr. Kanda reports grants from Kyowa Kirin, Sumitomo Pharma, Chugai, Takeda, and Eisai, and personal fees from Pfizer, Sumitomo Pharma, Novartis, Sanofi, Chugai, Symbio, Bristol Myers Squip, And Janssen, outside the submitted work. Dr. Teshima reports personal fees from Merck Sharp & Dohme; grants and personal fees from Kyowa Kirin; personal fees from Takeda, Pfizer, and Bristol‐Myers Squibb; grants from Chugai, Sanofi, Astellas, Teijin Pharma, Fuji Pharma, Nippon Shinyaku; non‐financial support from Janssen; and grants, personal fees, and non‐financial support from Novartis, outside the submitted work.

Figures

FIGURE 1
FIGURE 1
Overall survival: OS in (A) acute myelogenous leukemia (AML) and (B) acute lymphoblastic leukemia (ALL) conditioned with CY/TBI, CY/TBI+AraC, and CY/TBI+VP16 are shown separately.
FIGURE 2
FIGURE 2
Relapse: The cumulative incidence of relapse in (A) acute myelogenous leukemia (AML) and (B) acute lymphoblastic leukemia (ALL) conditioned with CY/TBI, CY/TBI+AraC, and CY/TBI+VP16 are shown separately.
FIGURE 3
FIGURE 3
TRM: Cumulative incidence of treatment‐related mortality (TRM) in (A) acute myelogenous leukemia (AML) and (B) acute lymphoblastic leukemia (ALL) conditioned with CY/TBI, CY/TBI+AraC, and CY/TBI+VP16 are shown separately.
See this image and copyright information in PMC

References

    1. Arai Y., Kondo T., Shigematsu A., et al., “High‐dose Cytarabine Added to CY/TBI Improves the Prognosis of Cord Blood Transplantation for Acute Lymphoblastic Leukemia in Adults: A Retrospective Cohort Study,” Bone Marrow Transplantation 51, no. 12 (2016): 1636–1639. - PubMed
    1. Arai Y., Takeda J., Aoki K., et al., “Efficiency of High‐dose Cytarabine Added to CY/TBI in Cord Blood Transplantation for Myeloid Malignancy,” Blood 126, no. 3 (2015): 415–422. - PMC - PubMed
    1. Arai Y., Aoki K., Takeda J., et al., “Clinical Significance of High‐dose Cytarabine Added to Cyclophosphamide/Total‐body Irradiation in Bone Marrow or Peripheral Blood Stem Cell Transplantation for Myeloid Malignancy,” Journal of Hematology & Oncology 8 (2015): 102. - PMC - PubMed
    1. Inamoto Y., Nishida T., Suzuki R., et al., “Significance of Additional High‐dose Cytarabine in Combination With Cyclophosphamide plus Total Body Irradiation Regimen for Allogeneic Stem Cell Transplantation,” Bone Marrow Transplantation 39, no. 1 (2007): 25–30. - PubMed
    1. Arai Y., Kondo T., Shigematsu A., et al., “Improved Prognosis With Additional Medium‐dose VP16 to CY/TBI in Allogeneic Transplantation for High Risk ALL in Adults,” American Journal of Hematology 93, no. 1 (2018): 47–57. - PubMed