Prophylactic role of long-term ultra-low-dose acyclovir for varicella zoster virus disease after allogeneic hematopoietic stem cell transplantation

Koji Kawamura, Hidenori Wada, Ryoko Yamasaki, Yuko Ishihara, Kana Sakamoto, Masahiro Ashizawa, Miki Sato, Tomohito Machishima, Kiriko Terasako, Shun ichi Kimura, Misato Kikuchi, Hideki Nakasone, Rie Yamazaki, Junya Kanda, Shinichi Kako, Aki Tanihara, Junji Nishida, Yoshinobu Kanda

Research output: Contribution to journalArticle

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Abstract

Objectives: To evaluate the prophylactic role of long-term ultra-low-dose acyclovir for varicella zoster virus (VZV) disease after allogeneic hematopoietic stem cell transplantation (HSCT). Methods: We evaluated 141 patients who were planned to receive acyclovir at 200. mg/day until the end of immunosuppressive therapy and for at least 1 year after HSCT in our center between June 2007 and June 2012. Results: The cumulative incidence of VZV disease after HSCT was 4.5% at 1 year and 18.3% at 2 years. Protocol violation was the only independent significant factor that increased the incidence of VZV disease (hazard ratio (HR) 7.50, 95% confidence interval (CI) 3.60-15.63). Excluding patients with protocol violation, the discontinuation of acyclovir was the only significant factor for the development of VZV disease (HR 5.90, 95% CI 1.56-22.37). Six patients experienced breakthrough VZV disease, but four of these six had not taken acyclovir for several weeks before breakthrough VZV disease. On the other hand, the cumulative incidence of VZV disease after the cessation of acyclovir was 28.4% at 1 year and 38.0% at 2 years. The proportion of disseminated VZV disease was only 7% and no patient died directly of VZV disease. Conclusions: This study shows that long-term ultra-low-dose acyclovir appears to be effective for preventing VZV disease, especially disseminated VZV disease, after allogeneic HSCT. We recommend continuing acyclovir until the end of immunosuppressive therapy and for at least 1 year after HSCT, but additional strategies such as the administration of varicella vaccine may be needed to eradicate VZV disease.

Original languageEnglish
Pages (from-to)26-32
Number of pages7
JournalInternational Journal of Infectious Diseases
Volume19
Issue number1
DOIs
Publication statusPublished - 2014 Feb 1
Externally publishedYes

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Human Herpesvirus 3
Acyclovir
Hematopoietic Stem Cell Transplantation
Virus Diseases
Immunosuppressive Agents
Incidence
Chickenpox Vaccine
Confidence Intervals

Keywords

  • Allogeneic hematopoietic stem cell transplantation
  • Disseminated VZV disease
  • Long-term acyclovir
  • Varicella zoster virus disease

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Prophylactic role of long-term ultra-low-dose acyclovir for varicella zoster virus disease after allogeneic hematopoietic stem cell transplantation. / Kawamura, Koji; Wada, Hidenori; Yamasaki, Ryoko; Ishihara, Yuko; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Machishima, Tomohito; Terasako, Kiriko; Kimura, Shun ichi; Kikuchi, Misato; Nakasone, Hideki; Yamazaki, Rie; Kanda, Junya; Kako, Shinichi; Tanihara, Aki; Nishida, Junji; Kanda, Yoshinobu.

In: International Journal of Infectious Diseases, Vol. 19, No. 1, 01.02.2014, p. 26-32.

Research output: Contribution to journalArticle

Kawamura, K, Wada, H, Yamasaki, R, Ishihara, Y, Sakamoto, K, Ashizawa, M, Sato, M, Machishima, T, Terasako, K, Kimura, SI, Kikuchi, M, Nakasone, H, Yamazaki, R, Kanda, J, Kako, S, Tanihara, A, Nishida, J & Kanda, Y 2014, 'Prophylactic role of long-term ultra-low-dose acyclovir for varicella zoster virus disease after allogeneic hematopoietic stem cell transplantation', International Journal of Infectious Diseases, vol. 19, no. 1, pp. 26-32. https://doi.org/10.1016/j.ijid.2013.09.020
Kawamura, Koji ; Wada, Hidenori ; Yamasaki, Ryoko ; Ishihara, Yuko ; Sakamoto, Kana ; Ashizawa, Masahiro ; Sato, Miki ; Machishima, Tomohito ; Terasako, Kiriko ; Kimura, Shun ichi ; Kikuchi, Misato ; Nakasone, Hideki ; Yamazaki, Rie ; Kanda, Junya ; Kako, Shinichi ; Tanihara, Aki ; Nishida, Junji ; Kanda, Yoshinobu. / Prophylactic role of long-term ultra-low-dose acyclovir for varicella zoster virus disease after allogeneic hematopoietic stem cell transplantation. In: International Journal of Infectious Diseases. 2014 ; Vol. 19, No. 1. pp. 26-32.
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abstract = "Objectives: To evaluate the prophylactic role of long-term ultra-low-dose acyclovir for varicella zoster virus (VZV) disease after allogeneic hematopoietic stem cell transplantation (HSCT). Methods: We evaluated 141 patients who were planned to receive acyclovir at 200. mg/day until the end of immunosuppressive therapy and for at least 1 year after HSCT in our center between June 2007 and June 2012. Results: The cumulative incidence of VZV disease after HSCT was 4.5{\%} at 1 year and 18.3{\%} at 2 years. Protocol violation was the only independent significant factor that increased the incidence of VZV disease (hazard ratio (HR) 7.50, 95{\%} confidence interval (CI) 3.60-15.63). Excluding patients with protocol violation, the discontinuation of acyclovir was the only significant factor for the development of VZV disease (HR 5.90, 95{\%} CI 1.56-22.37). Six patients experienced breakthrough VZV disease, but four of these six had not taken acyclovir for several weeks before breakthrough VZV disease. On the other hand, the cumulative incidence of VZV disease after the cessation of acyclovir was 28.4{\%} at 1 year and 38.0{\%} at 2 years. The proportion of disseminated VZV disease was only 7{\%} and no patient died directly of VZV disease. Conclusions: This study shows that long-term ultra-low-dose acyclovir appears to be effective for preventing VZV disease, especially disseminated VZV disease, after allogeneic HSCT. We recommend continuing acyclovir until the end of immunosuppressive therapy and for at least 1 year after HSCT, but additional strategies such as the administration of varicella vaccine may be needed to eradicate VZV disease.",
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AU - Kawamura, Koji

AU - Wada, Hidenori

AU - Yamasaki, Ryoko

AU - Ishihara, Yuko

AU - Sakamoto, Kana

AU - Ashizawa, Masahiro

AU - Sato, Miki

AU - Machishima, Tomohito

AU - Terasako, Kiriko

AU - Kimura, Shun ichi

AU - Kikuchi, Misato

AU - Nakasone, Hideki

AU - Yamazaki, Rie

AU - Kanda, Junya

AU - Kako, Shinichi

AU - Tanihara, Aki

AU - Nishida, Junji

AU - Kanda, Yoshinobu

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Objectives: To evaluate the prophylactic role of long-term ultra-low-dose acyclovir for varicella zoster virus (VZV) disease after allogeneic hematopoietic stem cell transplantation (HSCT). Methods: We evaluated 141 patients who were planned to receive acyclovir at 200. mg/day until the end of immunosuppressive therapy and for at least 1 year after HSCT in our center between June 2007 and June 2012. Results: The cumulative incidence of VZV disease after HSCT was 4.5% at 1 year and 18.3% at 2 years. Protocol violation was the only independent significant factor that increased the incidence of VZV disease (hazard ratio (HR) 7.50, 95% confidence interval (CI) 3.60-15.63). Excluding patients with protocol violation, the discontinuation of acyclovir was the only significant factor for the development of VZV disease (HR 5.90, 95% CI 1.56-22.37). Six patients experienced breakthrough VZV disease, but four of these six had not taken acyclovir for several weeks before breakthrough VZV disease. On the other hand, the cumulative incidence of VZV disease after the cessation of acyclovir was 28.4% at 1 year and 38.0% at 2 years. The proportion of disseminated VZV disease was only 7% and no patient died directly of VZV disease. Conclusions: This study shows that long-term ultra-low-dose acyclovir appears to be effective for preventing VZV disease, especially disseminated VZV disease, after allogeneic HSCT. We recommend continuing acyclovir until the end of immunosuppressive therapy and for at least 1 year after HSCT, but additional strategies such as the administration of varicella vaccine may be needed to eradicate VZV disease.

AB - Objectives: To evaluate the prophylactic role of long-term ultra-low-dose acyclovir for varicella zoster virus (VZV) disease after allogeneic hematopoietic stem cell transplantation (HSCT). Methods: We evaluated 141 patients who were planned to receive acyclovir at 200. mg/day until the end of immunosuppressive therapy and for at least 1 year after HSCT in our center between June 2007 and June 2012. Results: The cumulative incidence of VZV disease after HSCT was 4.5% at 1 year and 18.3% at 2 years. Protocol violation was the only independent significant factor that increased the incidence of VZV disease (hazard ratio (HR) 7.50, 95% confidence interval (CI) 3.60-15.63). Excluding patients with protocol violation, the discontinuation of acyclovir was the only significant factor for the development of VZV disease (HR 5.90, 95% CI 1.56-22.37). Six patients experienced breakthrough VZV disease, but four of these six had not taken acyclovir for several weeks before breakthrough VZV disease. On the other hand, the cumulative incidence of VZV disease after the cessation of acyclovir was 28.4% at 1 year and 38.0% at 2 years. The proportion of disseminated VZV disease was only 7% and no patient died directly of VZV disease. Conclusions: This study shows that long-term ultra-low-dose acyclovir appears to be effective for preventing VZV disease, especially disseminated VZV disease, after allogeneic HSCT. We recommend continuing acyclovir until the end of immunosuppressive therapy and for at least 1 year after HSCT, but additional strategies such as the administration of varicella vaccine may be needed to eradicate VZV disease.

KW - Allogeneic hematopoietic stem cell transplantation

KW - Disseminated VZV disease

KW - Long-term acyclovir

KW - Varicella zoster virus disease

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