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Incidence of refractory cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation

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Abstract

Post-transplant cytomegalovirus (CMV) disease can be almost completely avoided by current infection control procedures. However, CMV reactivation occurs in more than half of patients, and some patients can develop clinically resistant CMV infections. Whether resistance is due to the host’s immune status or a viral resistance mutation is challenging to confirm. Therefore, a prospective observational analysis of refractory CMV infection was conducted in 199 consecutive patients who received allogeneic hematopoietic stem cell transplantation at a single institution. Among them, 143 (72%) patients received anti-CMV drugs due to CMV reactivation, and only 17 (8.5%) exhibited refractory CMV infection. These patients had clinically refractory infection. However, viral genome analysis revealed that only one patient exhibited a mutation associated with the anti-CMV drug resistance. Clinical resistance was mainly correlated with host immune factors, and the incidence of resistance caused by gene mutations was low at the early stage after a transplantation.

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Acknowledgements

This work was supported by JSPS KAKENHI (Grant No: 18H02840).

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Authors and Affiliations

  1. Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, 812-8582, Japan

    Fumiaki Jinnouchi, Yasuo Mori, Goichi Yoshimoto, Takuji Yamauchi, Takuya Nunomura, Ayano Yurino, Masayasu Hayashi, Junichiro Yuda, Takahiro Shima, Jun Odawara, Shuichiro Takashima, Kenjiro Kamezaki, Koji Kato, Toshihiro Miyamoto & Koichi Akashi

  2. Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan

    Katsuto Takenaka

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Contributions

FJ and KT designed the study, performed the statistical analyses, wrote the manuscript, and collected the patient data. YM, GY, TY, TN, AY, MH, JY, SD, TS, JO, ST, KK, KK, TM and KA collected the patient data. All the authors analyzed and reviewed the data and approved the final version of the manuscript.

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Correspondence to Katsuto Takenaka.

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12185_2021_3218_MOESM1_ESM.pdf

Supplementary Figure 1 (PDF 111 KB) Maps of the UL54 and UL97 genes and amplified lesions. Red bars represent confirmed mutations associated with drug resistance (14). Four primer pairs were designed for the UL54 gene and two pairs for the UL97 gene. The arrows indicate the position and direction of the primers.

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Jinnouchi, F., Mori, Y., Yoshimoto, G. et al. Incidence of refractory cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Int J Hematol 115, 96–106 (2022). https://doi.org/10.1007/s12185-021-03218-3

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