TY - JOUR
T1 - Risk Factors and Predictive Scoring System For Post-Transplant Lymphoproliferative Disorder after Hematopoietic Stem Cell Transplantation
AU - Fujimoto, A.
AU - Hiramoto, Nobuhiro
AU - Yamasaki, Satoshi
AU - Inamoto, Yoshihiro
AU - Uchida, Naoyuki
AU - Maeda, Tetsuo
AU - Mori, Takehiko
AU - Kanda, Yoshinobu
AU - Kondo, Tadakazu
AU - Shiratori, Souichi
AU - Miyakoshi, Shigesaburo
AU - Ishiyama, Ken
AU - Ikegame, Kazuhiro
AU - Matsuhashi, Yoshiko
AU - Tanaka, J.
AU - Ichinohe, Tatsuo
AU - Atsuta, Yoshiko
AU - Ogata, M.
AU - Suzuki, Ritsuro
N1 - Funding Information:
The authors thank all the physicians and data managers at the centers who contributed to gathering data on transplantation to the Transplant Registry Unified Management Program and all the members of the Data Management Committees of JSHCT. Financial disclosure: This work was supported in part by the Practical Research Project for Allergic Disease and Immunology (Research Technology of Medical Transplantation) of the Japan Agency for Medical Research and Development. Conflict of interest statement: T. Mori (T.M.) has received research funding from Novartis, Asahi Kasei Pharma, and MSD and honoraria from Astellas Pharma, Kyowa Hakko Kirin, Shire, Japan Blood Products Organization, Pfizer, Chugai Pharmaceutical, Novartis, MSD, Janssen, Eisai, Ono Pharmaceutical, Celgene, Taisho Toyama Pharmaceutical, and Shionogi. Y.K. has received research funding from Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, Eisai, Chugai Pharmaceutical, Nippon Shinyaku, Astellas Pharma, Kyowa Hakko Kirin, Taiho Pharmaceutical, Pfizer, MSD, Takeda Pharmaceutical, Asahi Kasei Pharma, Ono Pharmaceutical, Sanofi, Novartis, Shionogi, Taisho Toyama Pharmaceutical, CSL Behring, and Tanabe Mitsubishi Pharma and honoraria and/or consultant fees from Astellas Pharma, Sumitomo Dainippon Pharma, Eisai, Kyowa Hakko Kirin, Takeda Pharmaceutical, Ono Pharmaceutical, Shionogi, Chugai Pharmaceutical, Bristol Myers Squibb, Celgene, Mochida Pharmaceutical, and Alexion Pharmaceuticals. J.T. has received research funding from Bristol Myers Squibb, Astellas Pharma, Chugai Pharmaceutical, Eisai, Kyowa Hakko Kirin, Mochida Pharma, MSD, Nippon Shinyaku, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Shionogi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and Teijin Pharma and honoraria from Astellas Pharma, Bristol Myers Squibb, Celgene, Chugai Pharmaceutical, Eisai, Kyowa Hakko Kirin, MSD, Nippon Shinyaku, Novartis, Otsuka Pharmaceutical, Pfizer, and Takeda Pharmaceutical. T.I. has received research funding from Astellas Pharma, Chugai Pharmaceutical, CSL Behring, Eisai, Kyowa Hakko Kirin, Ono Pharmaceutical, Pfizer, Nippon Shinyaku, MSD, Otsuka Pharmaceutical, Repertoire Genesis, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and Zenyaku Kogyo and honoraria from Alexion Pharmaceuticals, Bristol Myers Squibb, Celgene, JCR Pharmaceuticals, Janssen Pharmaceutical, Mundi Pharma, and Novartis. R.S. has received honoraria from Kyowa Hakko Kirin, Chugai Pharmaceutical, Meiji Seika, Bristol Myers Squibb, Sanofi, MSD, Takeda Pharmaceutical, Celgene, Eisai, Ono Pharmaceutical, Janssen Pharmaceutical, and Novartis and consultant fees from Mundi Pharma, Gilead Sciences, and Abbvie Pharmaceuticals. The other authors have no conflicts of interest to report. Financial disclosure: See Acknowledgments on page 1448.
Funding Information:
The authors thank all the physicians and data managers at the centers who contributed to gathering data on transplantation to the Transplant Registry Unified Management Program and all the members of the Data Management Committees of JSHCT. Financial disclosure: This work was supported in part by the Practical Research Project for Allergic Disease and Immunology (Research Technology of Medical Transplantation) of the Japan Agency for Medical Research and Development. Conflict of interest statement: T. Mori (T.M.) has received research funding from Novartis, Asahi Kasei Pharma, and MSD and honoraria from Astellas Pharma, Kyowa Hakko Kirin, Shire, Japan Blood Products Organization, Pfizer, Chugai Pharmaceutical, Novartis, MSD, Janssen, Eisai, Ono Pharmaceutical, Celgene, Taisho Toyama Pharmaceutical, and Shionogi. Y.K. has received research funding from Otsuka Pharmaceutical, Sumitomo DainipponPharma, Eisai, Chugai Pharmaceutical, Nippon Shinyaku, Astellas Pharma, Kyowa Hakko Kirin, Taiho Pharmaceutical, Pfizer, MSD, Takeda Pharmaceutical, Asahi Kasei Pharma, Ono Pharmaceutical, Sanofi, Novartis, Shionogi, Taisho Toyama Pharmaceutical, CSL Behring, and Tanabe Mitsubishi Pharma and honoraria and/or consultant fees from Astellas Pharma, Sumitomo Dainippon Pharma, Eisai, Kyowa Hakko Kirin, Takeda Pharmaceutical, Ono Pharmaceutical, Shionogi, Chugai Pharmaceutical, Bristol Myers Squibb, Celgene, Mochida Pharmaceutical, and Alexion Pharmaceuticals. J.T. has received research funding from Bristol Myers Squibb, Astellas Pharma, Chugai Pharmaceutical, Eisai, Kyowa Hakko Kirin, Mochida Pharma, MSD, Nippon Shinyaku, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Shionogi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and Teijin Pharma and honoraria from Astellas Pharma, Bristol Myers Squibb, Celgene, Chugai Pharmaceutical, Eisai, Kyowa Hakko Kirin, MSD, Nippon Shinyaku, Novartis, Otsuka Pharmaceutical, Pfizer, and Takeda Pharmaceutical. T.I. has received research funding from Astellas Pharma, Chugai Pharmaceutical, CSL Behring, Eisai, Kyowa Hakko Kirin, Ono Pharmaceutical, Pfizer, Nippon Shinyaku, MSD, Otsuka Pharmaceutical, Repertoire Genesis, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and Zenyaku Kogyo and honoraria from Alexion Pharmaceuticals, Bristol Myers Squibb, Celgene, JCR Pharmaceuticals, Janssen Pharmaceutical, Mundi Pharma, and Novartis. R.S. has received honoraria from Kyowa Hakko Kirin, Chugai Pharmaceutical, Meiji Seika, Bristol Myers Squibb, Sanofi, MSD, Takeda Pharmaceutical, Celgene, Eisai, Ono Pharmaceutical, Janssen Pharmaceutical, and Novartis and consultant fees from Mundi Pharma, Gilead Sciences, and Abbvie Pharmaceuticals. The other authors have no conflicts of interest to report. Financial disclosure: See Acknowledgments on page 8.
Funding Information:
Financial disclosure: This work was supported in part by the Practical Research Project for Allergic Disease and Immunology (Research Technology of Medical Transplantation) of the Japan Agency for Medical Research and Development .
Publisher Copyright:
© 2019 American Society for Blood and Marrow Transplantation
PY - 2019/7
Y1 - 2019/7
N2 - We analyzed data from 64,539 consecutive patients in the Japanese national transplant registry, including 40,195 after allogeneic hematopoietic stem cell transplantation (HSCT), 24,215 after autologous HSCT and 129 after syngeneic HSCT, of whom 299 developed Epstein-Barr virus-positive post-transplant lymphoproliferative disorder (PTLD). The probability of developing PTLD at 2 years post-HSCT was .79% after allogeneic transplantation, .78% after syngeneic transplantation, and .11% after autologous transplantation. The following variables were identified as risk factors after allogeneic HSCT in multivariate analysis: antithymocyte globulin (ATG) use in a conditioning regimen, ATG use for acute graft-versus-host disease (GVHD) treatment, donor other than an HLA-matched related donor, aplastic anemia, second or subsequent allogeneic HSCT, the most recent year of transplantation, and acute GVHD. The probability at 2 years increased particularly after 2009 (1.24%) than before 2009 (.45%). To stratify the risk of PTLD before allogeneic HSCT, we developed a novel 5-point scoring system based on 3 pretransplant risk factors: ATG use in a conditioning regimen (high dose, 2 points; low dose, 1 point), donor type (HLA-mismatched related donor, 1 point; unrelated donor, 1 point; cord blood, 2 points), and aplastic anemia (1 point). Patients were classified into 4 risk groups according to the summed points: low risk (0 or 1 point), intermediate risk (2 points), high risk (3 points), and very high risk (4 or 5 points) groups, with probabilities at 2 years of .3%, 1.3%, 4.6%, and 11.5%, respectively. Our scoring system is useful for predicting patients at high risk for PTLD. Careful observation and close monitoring of Epstein-Barr virus reactivation are warranted for these high-risk patients.
AB - We analyzed data from 64,539 consecutive patients in the Japanese national transplant registry, including 40,195 after allogeneic hematopoietic stem cell transplantation (HSCT), 24,215 after autologous HSCT and 129 after syngeneic HSCT, of whom 299 developed Epstein-Barr virus-positive post-transplant lymphoproliferative disorder (PTLD). The probability of developing PTLD at 2 years post-HSCT was .79% after allogeneic transplantation, .78% after syngeneic transplantation, and .11% after autologous transplantation. The following variables were identified as risk factors after allogeneic HSCT in multivariate analysis: antithymocyte globulin (ATG) use in a conditioning regimen, ATG use for acute graft-versus-host disease (GVHD) treatment, donor other than an HLA-matched related donor, aplastic anemia, second or subsequent allogeneic HSCT, the most recent year of transplantation, and acute GVHD. The probability at 2 years increased particularly after 2009 (1.24%) than before 2009 (.45%). To stratify the risk of PTLD before allogeneic HSCT, we developed a novel 5-point scoring system based on 3 pretransplant risk factors: ATG use in a conditioning regimen (high dose, 2 points; low dose, 1 point), donor type (HLA-mismatched related donor, 1 point; unrelated donor, 1 point; cord blood, 2 points), and aplastic anemia (1 point). Patients were classified into 4 risk groups according to the summed points: low risk (0 or 1 point), intermediate risk (2 points), high risk (3 points), and very high risk (4 or 5 points) groups, with probabilities at 2 years of .3%, 1.3%, 4.6%, and 11.5%, respectively. Our scoring system is useful for predicting patients at high risk for PTLD. Careful observation and close monitoring of Epstein-Barr virus reactivation are warranted for these high-risk patients.
KW - Hematopoietic stem cell transplantation
KW - Post-transplant lymphoproliferative disorder
KW - Predictive scoring system
UR - http://www.scopus.com/inward/record.url?scp=85063443813&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063443813&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2019.02.016
DO - 10.1016/j.bbmt.2019.02.016
M3 - Article
C2 - 30794929
AN - SCOPUS:85063443813
SN - 1083-8791
VL - 25
SP - 1441
EP - 1449
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 7
ER -