TY - JOUR
T1 - Novel Indicators of Transplant Outcomes for PhALL
T2 - Current Molecular-Relapse-Free Survival
AU - Nakasone, Hideki
AU - Kako, Shinichi
AU - Tachibana, Takayoshi
AU - Tanaka, Masatsugu
AU - Onizuka, Makoto
AU - Takahashi, Satoshi
AU - Yokota, Akira
AU - Fujiwara, Shin Ichiro
AU - Sakura, Toru
AU - Sakaida, Emiko
AU - Fujisawa, Shin
AU - Yamazaki, Rie
AU - Gotoh, Moritaka
AU - Hagihara, Maki
AU - Aotsuka, Nobuyuki
AU - Tsukada, Nobuhiro
AU - Hatta, Yoshihiro
AU - Shimizu, Hiroaki
AU - Usuki, Kensuke
AU - Watanabe, Reiko
AU - Mori, Takehiko
AU - Yano, Shingo
AU - Kanamori, Heiwa
AU - Kanda, Yoshinobu
N1 - Funding Information:
Conflict of interest statement: H.N. has received honoraria from Takeda Pharmaceutical, Otsuka Pharmaceutical, Bristol-Myers Squibb, Celgene, Pfizer, Novartis, Janssen Pharmaceutical, Eisai, Chugai Pharmaceutical, and Nippon Shinyaku. S.K. has received honoraria from Novartis and Bristol-Myers Squibb. T.T. has received personal fees from Otsuka, Novartis, Pfizer, Bristol-Myers Squibb, Daiichi Sankyo, and Astellas Pharma. S.-I.F. has received honoraria from Astellas Pharma, Celgene, Chugai Pharmaceutical, Eisai, Kyowa Kirin, Nippon Shinyaku, Novartis, Ortho Clinical Diagnostics, Otsuka Pharmaceutical, and Pfizer. S.F. has received honoraria from Novartis and Pfizer and research grants from Astellas Pharma, Chugai Pharmaceutical, and Pfizer. K.U. has received honoraria from Alexion Pharmaceuticals, SymBio Pharmaceuticals, Daiichi Sankyo, Otsuka Pharmaceutical, Novartis, Bristol-Myers Squibb, Ono Pharmaceutical, Celgene, Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Kyowa Kirin, Eisai, Merck Sharp & Dohme, SymBio Pharmaceuticals, PharmaEssentia, and Yakult and research grants from Astellas Pharma, Alexion Pharmaceuticals, AbbVie GK, Gilead, SymBio Pharmaceuticals, Daiichi Sankyo, Dainippon Sumitomo Pharma, Chugai Pharmaceutical, Otsuka Pharmaceutical, Novartis, Bristol-Myers Squibb, Ono Pharmaceutical, Janssen Pharmaceutical, Celgene, Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Mundipharma, Amgen Astellas BioPharma, Apellis Pharmaceuticals, Nippon Shinyaku, Kyowa Kirin, and Pfizer. E.S. has received honoraria from Bristol-Myers Squibb; research funds from Novartis, Pfizer, and Bristol-Myers Squibb; and subsidies from Kyowa Kirin, Chugai Pharmaceutical, and Ono Pharmaceutical. T.M. has received honoraria from Pfizer, Merck Sharp & Dohme, Janssen Pharmaceutical, Sumitomo Dainippon Pharma, Novartis, Kyowa Kirin, Chugai Pharmaceutical, Shionogi & Co., Japan Blood Products Organization, Takeda Pharmaceutical, Ono Pharmaceutical, Shire, Eisai, and Astellas Pharma and research funds from Astellas Pharma, Merck Sharp & Dohme, Novartis, LSI Medience, Medical & Biological Laboratories, and Asahi Kasei. S.Y. has received honoraria from Daiichi Sankyo and research grants from Kyowa Kirin, Astellas Pharma, Eli Lilly, Pfizer, Ono Pharmaceutical, Chugai Pharmaceutical, Mochida Pharmaceutical, Merck Sharp & Dohme, and Sumitomo Dainippon Pharma. Y.K. has received honoraria from Merck Sharp & Dohme, Astellas Pharma, Sumitomo Dainippon Pharma, Chugai Pharmaceutical, Pfizer, Novartis, Otsuka Pharmaceutical, Eisai, Janssen Pharmaceutical, Kyowa Kirin, Takeda Pharmaceutical, Ono Pharmaceutical, Shionogi & Co., Bristol-Myers Squibb, Celgene, Mochida Pharmaceutical, Alexion Pharmaceuticals, and Takara Bio and research grants from Celgene, Astellas Pharma, Chugai Pharmaceutical, Kyowa Kirin, Ono Pharmaceutical, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, Eisai, Shionogi & Co., Otsuka Pharmaceutical, Nippon-Shinyaku, Taiho, Pfizer, Merck Sharp & Dohme, Asahi-Kasei, Sanofi, Novartis, Taisho Toyama, CSL Behring, and Tanabe-Mitsubishi. The other authors report no potential competing conflicts of interest.
Publisher Copyright:
© 2021 The American Society for Transplantation and Cellular Therapy
PY - 2021/9
Y1 - 2021/9
N2 - Molecular relapse after allogeneic hematopoietic cell transplantation (allo-HCT) has been thought to predict clinical relapse in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (PhALL). Tyrosine kinase inhibitor (TKI) administration after allo-HCT may dynamically change the status from molecular relapse to molecular remission, but these state changes cannot be accurately represented by conventional survival indicators such as relapse-free survival, where events are usually considered irreversible. We aimed to develop novel indicators of transplant outcomes for allo-HCT recipients with PhALL and to visualize current molecular-relapse-free survival (CMRFS) and current on-TKI status (CTKI), treating molecular relapse or TKI administration after allo-HCT as a reversible event. We retrospectively analyzed 286 patients with PhALL who received allo-HCT between 2000 and 2016 in order to develop the indicators. CMRFS was defined as the probability of molecular remission without clinical relapse or death at any time after allo-HCT. Similarly, CTKI was defined as the probability of TKI administration without clinical relapse or death at any time after allo-HCT. The 1- and 5-year CMRFS rates were 67% and 59%, respectively, whereas the 1- and 5-year conventional molecular relapse-free survival rates were 42% and 37%. The 1- and 5-year CTKI rates were 14% and 8%, respectively. In a post hoc analysis focusing on patients who had achieved a molecular complete remission within 6 weeks (n = 201), the 5-year CMRFS rate (71%) was similar to the 5-year conventional molecular relapse-free survival (molRFS) rate (70%) in the non-TKI group. On the other hand, the 5-year CMRFS rate in the TKI group was 61%, whereas the 5-year conventional molRFS rate was only 38%. CMRFS and CTKI might become useful indicators of transplant success in terms of survival, leukemia-free status, and treatment-free status at any time point. Future extension of these survival models to other clinical situations is warranted.
AB - Molecular relapse after allogeneic hematopoietic cell transplantation (allo-HCT) has been thought to predict clinical relapse in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (PhALL). Tyrosine kinase inhibitor (TKI) administration after allo-HCT may dynamically change the status from molecular relapse to molecular remission, but these state changes cannot be accurately represented by conventional survival indicators such as relapse-free survival, where events are usually considered irreversible. We aimed to develop novel indicators of transplant outcomes for allo-HCT recipients with PhALL and to visualize current molecular-relapse-free survival (CMRFS) and current on-TKI status (CTKI), treating molecular relapse or TKI administration after allo-HCT as a reversible event. We retrospectively analyzed 286 patients with PhALL who received allo-HCT between 2000 and 2016 in order to develop the indicators. CMRFS was defined as the probability of molecular remission without clinical relapse or death at any time after allo-HCT. Similarly, CTKI was defined as the probability of TKI administration without clinical relapse or death at any time after allo-HCT. The 1- and 5-year CMRFS rates were 67% and 59%, respectively, whereas the 1- and 5-year conventional molecular relapse-free survival rates were 42% and 37%. The 1- and 5-year CTKI rates were 14% and 8%, respectively. In a post hoc analysis focusing on patients who had achieved a molecular complete remission within 6 weeks (n = 201), the 5-year CMRFS rate (71%) was similar to the 5-year conventional molecular relapse-free survival (molRFS) rate (70%) in the non-TKI group. On the other hand, the 5-year CMRFS rate in the TKI group was 61%, whereas the 5-year conventional molRFS rate was only 38%. CMRFS and CTKI might become useful indicators of transplant success in terms of survival, leukemia-free status, and treatment-free status at any time point. Future extension of these survival models to other clinical situations is warranted.
KW - Current molecular-relapse-free survival (CMRFS)
KW - Current on-TKI status (CTKI)
KW - Philadelphia chromosome–positive acute lymphoblastic leukemia (PhALL)
KW - Tyrosine kinase inhibitors (TKI)
UR - http://www.scopus.com/inward/record.url?scp=85111171662&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111171662&partnerID=8YFLogxK
U2 - 10.1016/j.jtct.2021.06.020
DO - 10.1016/j.jtct.2021.06.020
M3 - Article
C2 - 34171522
AN - SCOPUS:85111171662
SN - 2666-6375
VL - 27
SP - 800.e1-800.e8
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 9
ER -