Citations 2
Efficacy of Total‐Body Irradiation‐based Intensified Myeloablative Regimens for Acute Leukemia—An International Collaborative Study
Arai, Yasuyuki , Brazauskas, Ruta , He, Naya, Al‐Homsi, A. Samer, Yanada, Masamitsu , Steinberg, Amir , Hong, Sanghee , Bashey, Asad, Frangoul, Haydar , Verdonck, Leo F. , Aljurf, Mahmoud , Dias, Ajoy , Wirk, Baldeep , Freytes, César O. , Zeidan, Amer M., Lehmann, Leslie , Rangarajan, Hemalatha G. , Hashmi, Shahrukh K. , Yano, Shingo , Ozawa, Yukiyasu , Doki, Noriko, Kanda, Yoshinobu , Fukuda, Takahiro , Katayama, Yuta, Tanaka, Junji, Okamoto, Shinichiro , Saber, Wael , Yanada, Masamitsu , Kanda, Junya , Badawy, Sherif M , Sharma, Akshay , Abid, Muhammad Bilal , Wirk, Baldeep , Hashmi, Shahrukh, Kanda, Yoshinobu , Ichinohe, Tatsuo , Teshima, Takanori , Okamoto, Shinichiro , Atsuta, Yoshiko , Arai, Yasuyuki , Brazauskas, Ruta , Chhabra, Saurabh , Battiwalla, Minoo , Díaz, Miguel Ángel , Badawy, Sherif M. , Lazarus, Hillard M. , Yared, Jean A. , Hashem, Hasan , Sharma, Akshay , Abid, Muhammad Bilal , Zeidan, Amer M. , Gergis, Usama , Beitinjaneh, Amer , Askar, Medhat , Pu, Jeffrey J , Wood, William A. , Kako, Shinichi , Doki, Noriko , Katayama, Yuta
eJHaem | May 28, 2025 | Volume: 6 | Issue: 3 | Pages: No page available
ABSTRACTBackgroundIn 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).MethodsAdult 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.ResultsThe 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.ConclusionIn 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 RegistrationThe authors have confirmed clinical trial registration is not needed for this submission.
Reducing clinical trial eligibility barriers for patients with MDS: an icMDS position statement
Borate, Uma , Pugh, Kelly , Waller, Allyson, Welkie, Rina Li , Huang, Ying , Stahl, Maximilian , Platzbecker, Uwe , Wei, Andrew H. , Buckstein, Rena , Hasserjian, Robert P. , Fenaux, Pierre , Sallman, David A. , Nimer, Stephen D. , Little, Richard F. , Garcia‐Manero, Guillermo , Odenike, Olatoyosi, Kim, Tae Kon , Greenberg, Peter L. , Xu, Mina L. , Patnaik, Mrinal M. , Padron, Eric , Gore, Steven D. , Churpek, Jane E. , Bennett, John M., Brunner, Andrew M. , Zeidan, Amer M., Zeidan, Amer M. , Platzbecker, Uwe , Sekeres, Mikkael A , Wei, Andrew H , Roboz, Gail J , Loghavi, Sanam , Hasserjian, Robert P , Sallman, David A , Hourigan, Christopher S , Della Porta, Matteo Giovanni , Little, Richard F , Santini, Valeria , Taylor, Justin , Kim, Tae Kon , Halene, Stephanie , Komrokji, Rami S , Griffiths, Elizabeth A. , Greenberg, Peter L , Xie, Zhuoer , Sanz, Guillermo F , Patnaik, Mrinal , Carraway, Hetty E. , Boultwood, Jacqueline , Daver, Naval , Zeidan, Amer M , Churpek, Jane E , Bewersdorf, Jan Philipp , Dezern, Amy Elizabeth , Sekeres, Mikkael A. , Roboz, Gail J. , Savona, Michael R. , Loghavi, Sanam , Hourigan, Christopher S. , Santini, Valeria , Efficace, Fabio , Odenike, Olatoyosi , Komrokji, Rami S. , Xie, Zhuoer , Bejar, Rafael , Sanz, Guillermo , Figueroa, María E. , Abdel‐Wahab, Omar , Starczynowski, Daniel T. , Boultwood, Jacqueline , Daver, Naval , Majeti, Ravindra , List, Alan F. , Brunner, Andrew M., Churpek, Jane
Blood | March 27, 2025 | Volume: 145 | Issue: 13 | Pages: 1369-1381
Abstract Excessively restrictive inclusion and exclusion criteria in clinical trials are one of many barriers to clinical trial enrollment for patients with myelodysplastic syndromes/neoplasms (MDSs). Many organizations are developing efforts to increase clinical trial eligibility; yet, several recent publications focused on patients with MDS suggest that many patients with this disease may be excluded from clinical trials unnecessarily. Clinical trial eligibility should reflect the phase of the study and risks of the agent being studied. Phase 3 trials should be less restrictive than early-phase trials to represent the real-world population as closely as possible. We hypothesize that many clinical trials, particularly phase 3 trials, have unnecessarily restrictive eligibility criteria. This study aims to evaluate the most common eligibility criteria according to phase of trial and to determine whether criteria correspond with drug safety signals. We identified MDS clinical trials registered on ClinicalTrials.gov from 1 January 2000 to 1 September 2023 and analyzed the eligibility criteria of 191 therapeutic MDS trials. We found that categorical inclusion and exclusion criteria are remarkably similar in representation across trial phases. Additionally, only 13% of trials are concordant with drug safety signals, suggesting that the eligibility criteria are often arbitrary. On behalf of the icMDS (International Consortium for Myelodysplastic Syndromes), an association of international MDS experts, we provide a position statement on restrictive eligibility criteria for MDS clinical trials that should be avoided with the aim of removing barriers to clinical trial enrollment.