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Use of foscarnet for cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation from a related donor

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Abstract

Foscarnet is an active agent against cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT), as well as ganciclovir. We investigated the usefulness of foscarnet in patients who underwent related allogeneic HSCT. Foscarnet was used in 320 patients with a median age of 45 years (range 15–72). The purpose of administration was CMV disease in 65, preemptive use in 248 and prophylaxis in 7. Totally, 194 patients had a history of prior ganciclovir treatment. The reason for foscarnet use was insufficient therapeutic effect of prior ganciclovir in 99, and adverse event including myelosuppression in 95. The response rate in symptom was 52% for the CMV disease patients. Antigenemia disappeared in 77% of the preemptive treatment and improved in 13% of the patients. No outbreak of CMV disease was recognized. The total effectiveness of therapeutic and preemptive use was significantly higher for patients without prior ganciclovir (91 vs. 76%, P = 0.001). Adverse events of grade 3 or higher were recognized in 24%, including electrolyte abnormalities in 11%, neutropenia in 8%, and thrombocytopenia in 8%. Renal damage was only observed in 3% of patients. Foscarnet was concluded to be a safe and effective anti-CMV agent and to be a suitable alternative to ganciclovir.

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References

  1. Stocchi R, Ward KN, Fanin R, Baccarani M, Apperley JF. Management of human cytomegalovirus infection and disease after allogeneic bone marrow transplantation. Haematologica. 1999;84:71–9.

    CAS  PubMed  Google Scholar 

  2. Boeckh M. Current antiviral strategies for controlling cytomegalovirus in chematopoietic stem cell transplant recipients: prevention and therapy. Transpl Infect Dis. 1999;1:165–78.

    Article  CAS  PubMed  Google Scholar 

  3. Boeckh M, Nichols WG, Papanicolaou G, Rubin R, Wingard JR, Zaia J. Cytomegalovirus in hematopoietic stem cell transplant recipients: current status, known challenges, and future strategies. Biol Blood Marrow Transplant. 2003;9:543–58.

    Article  PubMed  Google Scholar 

  4. Yanada M, Yamamoto K, Emi N, Naoe T, Suzuki R, Taji H, Iida H, Shimokawa T, Kohno A, Mizuta S, Maruyama F, Wakita A, Kitaori K, Yano K, Hamaguchi M, Hamajima N, Morishima Y, Kodera Y, Sao H, Morishita Y. Cytomegalovirus antigenemia and outcome of patients treated with pre-emptive ganciclovir: retrospective analysis of 241 consecutive patients undergoing allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2003;32:801–7.

    Article  CAS  PubMed  Google Scholar 

  5. Biron K. Antiviral drugs for cytomegalovirus disease. Antiviral Res. 2006;71:154–63.

    Article  CAS  PubMed  Google Scholar 

  6. Goodrich JM, Mori M, Gleaves CA, Du Mond C, Cays M, Ebeling DF, Buhles WC, DeArmond B, Meyers JD. Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation. N Engl J Med. 1991;325:1601–7.

    Article  CAS  PubMed  Google Scholar 

  7. Goodrich JM, Bowden RA, Fisher L, Keller C, Schoch G, Meyers JD. Ganciclovir prophylaxis to prevent cytomegalovirus disease after allogeneic marrow transplant. Ann Intern Med. 1993;118:173–8.

    CAS  PubMed  Google Scholar 

  8. Winston DJ, Ho WG, Bartoni K, Du Mond C, Ebeling DF, Buhles WC, Champlin RE. Ganciclovir prophylaxis of cytomegalovirus infection and disease in allogeneic bone marrow transplant recipients. Results of a placebo-controlled, double-blind trial. Ann Intern Med. 1993;118:179–84.

    CAS  PubMed  Google Scholar 

  9. Salzberger B, Bowden RA, Hackman RC, Davis C, Boeckh M. Neutropenia in allogeneic marrow transplant recipients receiving ganciclovir for prevention of cytomegalovirus disease: risk factors and outcome. Blood. 1997;90:2502–8.

    CAS  PubMed  Google Scholar 

  10. Crumpacker CS. Ganciclovir. N Engl J Med. 1996;335:721–9.

    Article  CAS  PubMed  Google Scholar 

  11. Centers for Disease Control and Prevention, Infectious Diseases Society of America, American Society of Blood and Marrow Transplantation. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant. 2000;6(Suppl 6):7–83.

    Google Scholar 

  12. Baldanti F, Lurain N, Gerna G. Clinical and biologic aspects of human cytomegalovirus resistance to antiviral drugs. Hum Immunol. 2004;65:403–9.

    Article  CAS  PubMed  Google Scholar 

  13. Balfour HH Jr. Antiviral drugs. N Engl J Med. 1999;340:1255–68.

    Article  CAS  PubMed  Google Scholar 

  14. Ippoliti C, Morgan A, Warkentin D, van Besien K, Mehra R, Khouri I, Giralt S, Gajewski J, Champlin R, Andersson B, Przepiorka D. Foscarnet for prevention of cytomegalovirus infection in allogeneic marrow transplant recipients unable to receive ganciclovir. Bone Marrow Transplant. 1997;20:491–5.

    Article  CAS  PubMed  Google Scholar 

  15. Ordemann R, Naumann R, Geissler G, Kroschinsky F, Bornhäuser M, Schwerdtfeger R, Ehninger G. Foscarnet: an alternative for cytomegalovirus prophylaxis after allogeneic stem cell transplantation? Ann Hematol. 2000;79:432–6.

    Article  CAS  PubMed  Google Scholar 

  16. Reusser P, Gambertoglio JG, Lilleby K. Phase I-II trial of foscarnet for prevention of cytomegalovirus infection in autologous and allogeneic transplant recipients. J Infect Dis. 1992;166:473–9.

    CAS  PubMed  Google Scholar 

  17. Bacigalupo A, Tedone E, van Lint MT, Trespi G, Lonngren M, Sanna MA, Moro F, Frassoni F, Occhini D, Gualandi F, et al. CMV prophylaxis with foscarnet in allogeneic bone marrow transplant recipients at high risk of developing CMV infection. Bone Marrow Transplant. 1994;13:783–8.

    CAS  PubMed  Google Scholar 

  18. Moretti S, Zikos P, van Lint MT, Tedone E, Occhini D, Gualandi F, Lamparelli T, Mordini N, Berisso G, Bregante S, Bruno B, Bacigalupo A. Foscarnet vs ganciclovir for cytomegalovirus (CMV) antigenemia after allogeneic hemopoietic stem cell transplantation (HSCT): a randomised study. Bone Marrow Transplant. 1998;22:175–80.

    Article  CAS  PubMed  Google Scholar 

  19. Reusser P, Einsels H, Lee J, Volin L, Rovira M, Engelhard D, Finke J, Cordonnier C, Link H, Ljungman P. Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation. Blood. 2002;99:1159–64.

    Article  CAS  PubMed  Google Scholar 

  20. Matsumura T, Narimatsu H, Kami M, Yuji K, Kusumi E, Hori A, Murashige N, Tanaka Y, Masuoka K, Wake A, Miyakoshi S, Kanda Y, Taniguchi S. Cytomegalovirus infections following umbilical cord blood transplantation using reduced intensity conditioning regimens for adult patients. Biol Blood Marrow Transplant. 2007;13:577–83.

    Article  PubMed  Google Scholar 

  21. Atsuta Y, Suzuki R, Yoshimi A, Gondo H, Tanaka J, Hiraoka A, Kato K, Tabuchi K, Tsuchida M, Morishima Y, Mitamura M, Kawa K, Kato S, Nagamura T, Takanashi M, Kodera Y. Unification of hematopoietic stem cell transplantation registries in Japan and establishment of the TRUMP system. Int J Hematol. 2007;86:269–74.

    Article  PubMed  Google Scholar 

  22. Kanda Y, Mineishi S, Saito T, Seo S, Saito A, Suenaga K, Ohnishi M, Niiya H, Nakai K, Takeuchi T, Kawahigashi N, Shoji N, Ogasawara T, Tanosaki R, Kobayashi Y, Tobinai K, Kami M, Mori S, Suzuki R, Kunitoh H, Takaue Y. Pre-emptive therapy against cytomegalovirus (CMV) disease guided by CMV antigenemia assay after allogeneic haematopoietic stem cell transplantation: a single-center experience in Japan. Bone Marrow Transplant. 2001;27:437–44.

    Article  CAS  PubMed  Google Scholar 

  23. Mori T, Mori S, Kanda Y, Yakushiji K, Mineishi S, Takaue Y, Gondo H, Harada M, Sakamaki H, Yajima T, Iwao Y, Hibi T, Okamoto S. Clinical significance of cytomegalovirus (CMV) antigenemia in the prediction and diagnosis of CMV gastrointestinal disease after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2004;33:431–4.

    Article  CAS  PubMed  Google Scholar 

  24. Ljungman PG, Oberg G, Aschan J, Ehrnst A, Lönnqvist B, Pauksen K, Sulila P. Foscarnet for pre-emptive therapy of CMV infection detected by a leukocyte-based nested PCR in allogeneic bone marrow transplant patients. Bone Marrow Transplant. 1996;18:565–8.

    CAS  PubMed  Google Scholar 

  25. Bregante S, Bertilson S, Tedone E, Van Lint MT, Trespi G, Mordini N, Berisso G, Gualandi F, Lamparelli T, Figari O, Benvenuto F, Raiola AM, Bacigalupo A. Foscarnet prophylaxis of cytomegalovirus infections in patients undergoing allogeneic bone marrow transplantation (BMT): a dose-finding study. Bone Marrow Transplant. 2000;26:23–9.

    Article  CAS  PubMed  Google Scholar 

  26. Narimatsu H, Kami M, Kato D, Matsumura T, Murashige N, Kusumi E, Yuji K, Hori A, Shibata T, Masuoka K, Wake A, Miyakoshi S, Morinaga S, Taniguchi S. Reduced dose of foscarnet as preemptive therapy for cytomegalovirus infection following reduced-intensity cord blood transplantation. Transpl Infect Dis. 2007;9:11–5.

    Article  CAS  PubMed  Google Scholar 

  27. Wang H, Zhu L, Xue M, Liu J, Guo Z. Low-dose foscarnet preemptive therapy for cytomegalovirus viremia after haploidentical bone marrow transplantation. Biol Blood Marrow Transplant. 2009;15:519–20.

    Article  CAS  PubMed  Google Scholar 

  28. Mattes FM, Hainsworth EG, Geretti AM, Nebbia G, Prentice G, Potter M, Burroughs AK, Sweny P, Hassan-Walker AF, Okwuadi S, Sabin C, Amooty G, Brown VS, Grace SC, Emery VC, Griffiths PD. A randomized, controlled trial comparing ganciclovir to ganciclovir plus foscarnet (each at half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients. J Infect Dis. 2004;189:1355–61.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by Health and Labour Sciences Research Grants for Clinical Cancer Research from the Ministry of Health, Labour, and Welfare, Japan. The authors would like to thank the staff of the Data Center of the Japan Society for Hematopoietic Cell Transplantation and the following collaborating institutions for providing patient data and specimens: Hokkaido University; Sapporo Hokuyu Hospital; Asahikawa Medical College; Hakodate Municipal Hospital; Aomori Prefectural Central Hospital; Tohoku University; Akita University; Kita-Fukushima Medical Center; Tsukuba University; Gunma University; Saitama Medical University International Medical Center; Matsudo Municipal Hospital; National Cancer Center Hospital; Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital; Jikei University; Keio University; Tokyo Women’s Medical University; Teikyo University; NTT Kanto Medical Center; Toranomon Hospital; Tokyo Medical and Dental University; National Hospital Organization Tokyo Medical Center; Yokohama City University; Kanagawa Cancer Center; Yokohama City University Medical Center; St. Marianna University; St. Marianna University Yokohama City Seibu Hospital; Niigata University; Niigata Cancer Center; Nagaoka Red Cross Hospital; Toyama Prefectural Central Hospital; Kanazawa University; Shinshu University; Gifu University; Hamamatsu Medical University; Meitetsu Hospital; Nagoya City University; Social insurance Chukyo Hospital; Mie University; Suzuka Kaisei Hospital; Kyoto University; Social Insurance Kyoto Hospital; Kyoto City Hospital; Kyoto Katsura Hospital; Osaka Medical Center For Cancer And Cardiovascular Diseases; Kinki University; Hyogo College of Medicine; Osaka City University; Matsushita Memorial Hospital; Rinku General Medical Center Izumisano Municipal Hospital; Osaka Medical College; Kansai Medical University Hirakata Hospital; Hyogo Cancer Center; Shimane Prefectural Central Hospital; Kurashiki Central Hospital; Okayama University; National Hospital Organization Kure Medical Center; Yamaguchi University; Tokushima University; Kyushu University; Hamanomachi Hospital; Nagasaki University; Sasebo City General Hospital; National Hospital Organization Nagasaki Medical Center; National Hospital Organization Kumamoto Medical Center; Oita University.

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Authors and Affiliations

  1. Department of HSCT Data Management and Biostatistics, Nagoya University School of Medicine, 1-1-20 Daiko-minami, Higashi-ku, Nagoya, 461-0047, Japan

    Maiko Asakura, Yoshiko Atsuta & Ritsuro Suzuki

  2. Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan

    Kazuhiro Ikegame, Satoshi Yoshihara & Hiroyasu Ogawa

  3. Department of Hematology, Toranomon Hospital, Tokyo, Japan

    Shuichi Taniguchi

  4. Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

    Takehiko Mori

  5. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan

    Tetsuya Etoh

  6. Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan

    Akiyoshi Takami

  7. Hematology Department, Toyama Prefectural Hospital, Toyama, Japan

    Takashi Yoshida

  8. Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan

    Takahiro Fukuda

  9. Department of Internal Medicine, Rinku General Medical Center, Izumisano, Japan

    Kazuo Hatanaka

  10. Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan

    Heiwa Kanamori

  11. Third Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan

    Toshiaki Yujiri

  12. Department of Hematology, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan

    Hisashi Sakamaki

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  1. Maiko Asakura
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  2. Kazuhiro Ikegame
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  3. Satoshi Yoshihara
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  4. Shuichi Taniguchi
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  6. Tetsuya Etoh
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  7. Akiyoshi Takami
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  8. Takashi Yoshida
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  9. Takahiro Fukuda
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  11. Heiwa Kanamori
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  12. Toshiaki Yujiri
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  13. Yoshiko Atsuta
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  14. Hisashi Sakamaki
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  15. Ritsuro Suzuki
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  16. Hiroyasu Ogawa
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Corresponding author

Correspondence to Ritsuro Suzuki.

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Asakura, M., Ikegame, K., Yoshihara, S. et al. Use of foscarnet for cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation from a related donor. Int J Hematol 92, 351–359 (2010). https://doi.org/10.1007/s12185-010-0657-y

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  • DOI: https://doi.org/10.1007/s12185-010-0657-y

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