Risk Factors and Predictive Scoring System For Post-Transplant Lymphoproliferative Disorder after Hematopoietic Stem Cell Transplantation

Ayumi Fujimoto; Nobuhiro Hiramoto; Satoshi Yamasaki; Yoshihiro Inamoto; Naoyuki Uchida; Tetsuo Maeda; Takehiko Mori; Yoshinobu Kanda; Tadakazu Kondo; Souichi Shiratori; Shigesaburo Miyakoshi; Ken Ishiyama; Kazuhiro Ikegame; Yoshiko Matsuhashi; Junji Tanaka; Tatsuo Ichinohe; Yoshiko Atsuta; Masao Ogata; Ritsuro Suzuki

doi:10.1016/j.bbmt.2019.02.016

Risk Factors and Predictive Scoring System For Post-Transplant Lymphoproliferative Disorder after Hematopoietic Stem Cell Transplantation

Biol Blood Marrow Transplant. 2019 Jul;25(7):1441-1449. doi: 10.1016/j.bbmt.2019.02.016. Epub 2019 Feb 20.

Authors

Ayumi Fujimoto¹, Nobuhiro Hiramoto², Satoshi Yamasaki³, Yoshihiro Inamoto⁴, Naoyuki Uchida⁵, Tetsuo Maeda⁶, Takehiko Mori⁷, Yoshinobu Kanda⁸, Tadakazu Kondo⁹, Souichi Shiratori¹⁰, Shigesaburo Miyakoshi¹¹, Ken Ishiyama¹², Kazuhiro Ikegame¹³, Yoshiko Matsuhashi¹⁴, Junji Tanaka¹⁵, Tatsuo Ichinohe¹⁶, Yoshiko Atsuta¹⁷, Masao Ogata¹⁸, Ritsuro Suzuki¹⁹

Affiliations

¹ Department of Oncology and Hematology, Shimane University Hospital, Izumo, Japan; Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan.
² Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan.
³ Department of Hematology and Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan.
⁴ Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
⁵ Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations, Toranomon Hospital, Tokyo, Japan.
⁶ Department of Hematology and Oncology, Osaka University Hospital, Osaka, Japan.
⁷ Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
⁸ Division of Hematology, Saitama Medical Center Jichi Medical University, Saitama, Japan.
⁹ Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹⁰ Department of Hematology, Hokkaido University Hospital, Sapporo, Japan.
¹¹ Department of Hematology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
¹² Department of Hematology, Kanazawa University Hospital, Kanazawa, Japan.
¹³ Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
¹⁴ Department of Hematology, Kawasaki Medical School Hospital, Kurashiki, Japan.
¹⁵ Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan.
¹⁶ Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
¹⁷ Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan; Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹⁸ Department of Hematology, Oita University Faculty of Medicine, Oita, Japan.
¹⁹ Department of Oncology and Hematology, Shimane University Hospital, Izumo, Japan. Electronic address: rsuzuki@med.shimane-u.ac.jp.

PMID: 30794929
DOI: 10.1016/j.bbmt.2019.02.016

Abstract

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.

Keywords: Hematopoietic stem cell transplantation; Post-transplant lymphoproliferative disorder; Predictive scoring system.

Publication types

Clinical Trial
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Allografts
Anemia, Aplastic* / epidemiology
Anemia, Aplastic* / therapy
Anemia, Aplastic* / virology
Antilymphocyte Serum / administration & dosage*
Autografts
Epstein-Barr Virus Infections* / epidemiology
Epstein-Barr Virus Infections* / etiology
Female
Graft vs Host Disease* / etiology
Graft vs Host Disease* / prevention & control
Hematopoietic Stem Cell Transplantation*
Herpesvirus 4, Human*
Humans
Lymphoproliferative Disorders* / epidemiology
Lymphoproliferative Disorders* / etiology
Lymphoproliferative Disorders* / virology
Male
Middle Aged
Risk Assessment
Risk Factors
Transplantation Conditioning*
Transplantation, Isogeneic

Substances

Antilymphocyte Serum