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.
Gilteritinib as Post-Transplant Maintenance for AML With Internal Tandem Duplication Mutation of FLT3
Levis, Mark J. , Hamadani, Mehdi , Logan, Brent R. , Jones, Richard J. , Singh, Anurag K. , Litzow, Mark R. , Wingard, John R. , Papadopoulos, Esperanza B. , Perl, Alexander E. , Soiffer, Robert J. , Üstün, Celalettin , Uy, Geoffrey L. , Vasu, Sumithra, Solh, Melhem , Mishra, Asmita , Muffly, Lori , Mikesch, Jan‐Henrik , Onozawa, Masahiro , Thomson, Kirsty , Nagler, Arnon , Marcucci, Guido , Geller, Nancy L. , Hasabou, Nahla, Delgado, David, Rosales, Matt, Hill, Jason E. , Gill, Stanley C. , Nuthethi, Rishita, King, Denise , Wittsack, Heather, Mendizabal, Adam , Horowitz, Mary M. , Chen, Yi‐Bin , Investigators, on behalf of the BMT-CTN 1506/MORPHO Study, Agura, Ed, Altman, Jessica K. , Anagnostopoulos, Achiles, Aulitzky, Walter E. , Balderman, Sophia , Ballen, Karen K. , Béguin, Yves , Berkahn, Leanne, Bilmon, Ian , Briggs, Adrienne, Brunstein, Claudio G. , Byrne, Michael , Carrum, George, Černý, Jan , Ciceri, Fabio , Colorado, Mercedes , Cook, Rachel J. , Couriel, Daniel R. , Damon, Lloyd E. , Deol, Abhinav , Desbrosses, Yohan, Devine, Steve, Grazia, Carmela Di, Stasi, Antonio Di , Dias, Ajoy , Dorritie, Kathy, Essell, James , Eto, Tetsuya , Forcade, Édouard , Frankfurt, Olga, Fukuda, Takahiro , Fürst, Sabine , Goto, Tatsunori , Hall, Aric C. , Hatta, Shunsuke , Hicheri, Yosr , Horwitz, Mitchell E. , How, Jonathan, Howard, Dianna S. , Hsu, Wei‐Hsun , Huynh, Anne , Irvine, David, Ishikawa, Takayuki , Jamieson, Katarzyna , Wiktor-Jędrzejczak, W , Karakasis, Dimitrios, Kato, Jun , Kekre, Natasha , Khera, Nandita , Klein, A. , Kobbe, Guido , Kornblit, Brian, Lachance, Silvy , Levis, Mark J., Lin, Tung‐Liang , Litzow, Mark, Liu, Ta‐Chih, Martelli, Maurizio , Matsuoka, Ken‐ichi , McCarty, John M. , Mendez, Lourdes , Michelis, Fotios V. , Mikesch, Jan-Henrik, Mineishi, Shin , Moors, Ine , Motyckova, Gabriela, Mueller, Lutz Peter , Muffly, Lori, Nakamae, Hirohisa , Nathan, Sunita , Norkin, Maxim , Ogawa, Yoshiaki, Olesen, G., Onozawa, Masahiro, Paulson, Kristjan, Pemberton, Lucy, Perera, Travis, Perl, Alexander E., Piątkowska‐Jakubas, Beata, Protheroe, Rachel, Ross, Kelly , Santarone, Stella , Sawa, Masashi , Schaar, Dale , Scheid, Christoph, Schriber, Jeffrey, Seropian, Stuart , Shah, Nilay , Shah, Nirav N. , Gil, Jorge Sierra, Sobecks, Ronald , Sprague, Kellie , Spyridonidis, Alexandros , Stelljes, Matthias , Stiff, Patrick J. , Tandra, Anand, Tholouli, Eleni , Thomas, Xavier , Tomlinson, Benjamin , Ustun, Celalettin, Uy, Geoffrey L., Ferreiras, David Valcarcel, Wagner, Eva , Watson, Anne-Marie, Wolschke, Christine, Yamauchi, Takuji , Yeh, Su‐Peng , Logan, Brent , Litzow, Mark R. , Ueda Oshima, Masumi , Uy, Geoffrey , Waller, Edmund K , Solh, Melham M , Mishra, Asmita , Muffly, Lori , Kim, Hee-Je , Najima, Yuho , Onozawa, Masahiro , Nagler, Arnon , Wei, Andrew H , Geller, Nancy , Hill, Jason , Gill, Stanley C , King, Denise , Devine, Steven , Horowitz, Mary , Chen, Yi-Bin , Hamadani, Mehdi , Ueda, Masumi , Waller, Edmund K. , Wei, Andrew H. , Devine, Steven M. , Investigators, on behalf of the BMT-CTN 1506/MORPHO Study, Anagnostopoulos, Achiles, Anand, Sarah , Artz, Andrew , Becker, Michael W. , Berneman, Zwi Nisan , Bhatt, Vijaya Raj , Bonifazi, Francesca , Bruno, Benedetto , Byrne, Jenny , Cabrero, Mónica , Cairoli, Roberto , Cheong, June‐Won , Colorado, Mercedes , Craddock, Charles , Grazia, Carmela Di, Farag, Sherif Shafik , Fujiwara, Shin‐ichiro , Fukushima, Kentaro , Hou, Hsin‐An , Jethava, Yogesh S. , Jiménez, Antonio , Jung, Chul Won , Kanda, Junya , Klein, Andreas, Kota, Vamsi , Leber, Brian F. , Lee, Catherine J , Lee, Je‐Hwan , Levis, Mark J., Litzow, Mark, Martínez, Carmen , Mikesch, Jan-Henrik, Mohty, Mohamad , Mueller, Lutz, Muffly, Lori, Nakano, Nobuaki , Nicholson, Emma , Oluwole, Olalekan O. , Onozawa, Masahiro, Pantin, Jeremy , Perl, Alexander E., Poiré, Xavier , Rambaldi, Alessandro , Ritchie, David , Rubio, Marie‐Thérèse , Sanz, Jaime , Shore, Tsiporah B. , Socié, Gèrard , Stuart, Robert K. , Tanaka, Masatsugu , Tiribelli, Mario , Tsirigotis, Panagiotis D. , Tzachanis, Dimitrios , Uchida, Naoyuki , Ustun, Celalettin, Uy, Geoffrey L., Ferreiras, David Valcarcel, Weisdorf, Daniel J. , Wróbel, Tomasz , Yakoub‐Agha, Ibrahim , Yared, Jean A. , Yoon, Sung‐Soo , Yoshihara, Satoshi
Journal of Clinical Oncology | March 12, 2024 | Volume: 42 | Issue: 15 | Pages: 1766-1775
PURPOSE Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 ( FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202 ) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.