Association Between Candidemia and Noninfectious Interstitial Pneumonia After Allogeneic Hematopoietic Cell Transplantation: JSTCT Transplant Complications Working Group

Shun-Ichi Kimura; Yu Akahoshi; Souichi Shiratori; Keiji Okinaka; Kaito Harada; Naoyuki Uchida; Noriko Doki; Kazuhiro Ikegame; Hirohisa Nakamae; Masatsugu Tanaka; Satoru Takada; Toshiro Kawakita; Ken-Ichi Matsuoka; Takahide Ara; Shuichi Ota; Masashi Sawa; Makoto Onizuka; Takahiro Fukuda; Yoshiko Atsuta; Yoshinobu Kanda; Hideki Nakasone

doi:10.1093/ofid/ofad163

Association Between Candidemia and Noninfectious Interstitial Pneumonia After Allogeneic Hematopoietic Cell Transplantation: JSTCT Transplant Complications Working Group

Open Forum Infect Dis. 2023 Mar 27;10(4):ofad163. doi: 10.1093/ofid/ofad163. eCollection 2023 Apr.

Authors

Shun-Ichi Kimura^{1

2}, Yu Akahoshi^{1

2

3}, Souichi Shiratori^{2

4}, Keiji Okinaka^{2

5

6}, Kaito Harada^{2

7}, Naoyuki Uchida⁸, Noriko Doki⁹, Kazuhiro Ikegame¹⁰, Hirohisa Nakamae¹¹, Masatsugu Tanaka¹², Satoru Takada¹³, Toshiro Kawakita¹⁴, Ken-Ichi Matsuoka¹⁵, Takahide Ara⁴, Shuichi Ota¹⁶, Masashi Sawa¹⁷, Makoto Onizuka⁷, Takahiro Fukuda⁶, Yoshiko Atsuta^{18

19}, Yoshinobu Kanda^{1

20}, Hideki Nakasone^{1

2}

Affiliations

¹ Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan.
² Transplant Complications Working Group of the Japan Society for Transplantation and Cellular Therapy (JSTCT), Aichi, Japan.
³ Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁴ Department of Hematology, Hokkaido University Hospital, Hokkaido, Japan.
⁵ Department of General Medicine and Infectious Diseases, National Cancer Center Hospital East, Chiba, Japan.
⁶ Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
⁷ Department of Hematology and Oncology, Tokai University School of Medicine, Kanagawa, Japan.
⁸ Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital, Tokyo, Japan.
⁹ Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
¹⁰ Department of Hematology, Hyogo College of Medicine Hospital, Hyogo, Japan.
¹¹ Department of Hematology, Osaka Metropolitan University Hospital, Osaka, Japan.
¹² Department of Hematology, Kanagawa Cancer Center, Kanagawa, Japan.
¹³ Leukemia Research Center, Saiseikai Maebashi Hospital, Gunma, Japan.
¹⁴ Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan.
¹⁵ Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan.
¹⁶ Department of Hematology, Sapporo Hokuyu Hospital, Hokkaido, Japan.
¹⁷ Department of Hematology and Oncology, Anjo Kosei Hospital, Aichi, Japan.
¹⁸ Japanese Data Center for Hematopoietic Cell Transplantation, Aichi, Japan.
¹⁹ Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Aichi, Japan.
²⁰ Division of Hematology, Jichi Medical University, Tochigi, Japan.

Abstract

Background: α-mannan from Candida albicans reportedly induces Th17-mediated pulmonary graft-versus-host disease (GVHD) in mouse models. This study aimed to evaluate the association between candidemia and noninfectious interstitial pneumonia (IP) in allogeneic hematopoietic cell transplantation (HCT) recipients.

Methods: Using a Japanese transplant registry database, we analyzed 9143 pediatric and adult patients with hematological malignancies who underwent their first (n = 7531) or second (n = 1612) allogeneic HCT between 2009 and 2019.

Results: Noninfectious IP was observed in 694 patients at a median (range) of 63 (0-1292) days after HCT. Candidemia occurred in 358 patients at a median (range) of 31 (0-903) days after HCT. Candidemia treated as a time-dependent covariate was significantly associated with an increased incidence of noninfectious IP (hazard ratio [HR], 2.51; 95% CI, 1.48-4.25), along with total body irradiation (>8 Gy; HR, 1.57; 95% CI, 1.18-2.10) and malignant lymphoma (vs acute myeloid leukemia; HR, 1.30; 95% CI, 1.004-1.69). On the other hand, prompt platelet recovery (HR, 0.58; 95% CI, 0.45-0.75) and acute lymphoblastic leukemia (vs acute myeloid leukemia; HR, 0.68; 95% CI, 0.49-0.94) were associated with reduced incidence of noninfectious IP. The median survival after the development of noninfectious IP in patients with prior candidemia was significantly shorter than that in those without it (22 days vs 59 days; P < .001).

Conclusions: Candidemia was associated with an increased incidence of noninfectious IP. The prognosis of noninfectious IP after candidemia was extremely poor.

Keywords: candidemia; hematopoietic cell transplantation–specific comorbidity index; idiopathic pneumonia syndrome; interstitial pneumonia; platelet recovery.