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• W2003177761 abstract "The use of all-trans retinoic acid in routine clinical practice has changed the outcome of acute promyelocytic leukemia (APL) from a deadly disease to the most curable subtype of acute myeloid leukemia. Introduction of arsenic trioxide (ATO) further improved the long-term survival of patients with APL [1]. Although adverse effects of ATO, including prolonged QT interval, rash, and pigmentation, are relatively mild and manageable, herpes zoster infection has been sporadically reported in patients with ATO treatment [2,3,4]. However, the incidence and clinical features of varicella zoster virus (VZV) reactivation associated with ATO treatment have not been examined in detail. To explore the characteristics of VZV reactivation in APL patients receiving ATO therapy, we retrospectively analyzed the association between ATO use and the occurrence of VZV infection in patients with APL at our hospital.We identified 25 patients with APL from January 2000 to September 2012. Two patients died due to cerebral hemorrhage soon after diagnosis and were excluded from the analysis. Among the remaining 23 patients, 15 received ATO-containing chemotherapy. The median age of these 23 patients was 59 years (range: 25-81 years) and the observation period was 41 months (range: 5-136 months). In the group of patients treated with ATO, 5 were given an ATO regimen as first-line induction therapy, 6 were given ATO as consolidation chemotherapy, and the remaining 4 were given ATO as salvage therapy. One patient died soon after relapse because of sepsis. VZV reactivation was diagnosed by characteristic clinical features and confirmed by a dermatologist.VZV reactivation occurred in 7 of the 15 patients (46.7%) treated with ATO, but in none of those without ATO treatment (30%). VZV reactivation occurred after ATO treatment in all cases. ATO use was significantly associated with the development of VZV reactivation compared to those treated without ATO (25.9 and 0%; p = 0.008, respectively). There were no significant differences in clinical variables, including sex (male/female; 3/4 vs. 9/11), age (median; 60.5 vs. 58 years), and corticosteroid use (>140 mg/week; 22.2 vs. 31.8%), between the patients with and without ATO (table 1). The median time of VZV reactivation was 72 days (range: 40-146 days) from the start of ATO administration, and the total ATO dose at the time of reactivation was 5.7 mg/kg (range 4.05-9.9 mg/kg). VZV reactivation occurred during ATO treatment in 6 patients and after ATO treatment in 1 patient. Disseminated zoster was seen in 1 patient. All patients responded promptly to treatment with acyclovir or valacyclovir and did not develop postherpetic neuralgia. There were no cases of viral infection other than VZV.Although the appearance of herpetic infection after long-term exposure to arsenic has been known from the mid-1900s, clinical features of VZV reactivation associated with therapeutic use of ATO have not been well defined. We examined several predisposing factors, including age, gender, use of ATO, and corticosteroid use, and only ATO use showed a positive correlation with the development of VZV. Consistent with a previous report [3], VZV reactivation occurred relatively early after the start of ATO therapy.The mechanism of VZV reactivation in patients treated with ATO remains unclear. An increased incidence of VZV reactivation is generally observed in elderly and/ or immunosuppressed individuals, suggesting impaired VZV-specific T cell function in these individuals. ATO can induce apoptosis of normal T helper cells [5,6] and possibly an increase in susceptibility to VZV infection in these patients. Inhibition of the nuclear factor κB-mediated antiviral effect by ATO is another possible mechanism of action induced by the use of ATO [7], although no increases in the incidence of other viral infections have been reported to date.Although the incidence of VZV reactivation in patients treated with ATO was high, all of the patients who developed VZV infection were successfully treated and persistent neuralgia did not occur in our series. Therefore, we did not routinely use acyclovir prophylaxis for these patients.In conclusion, VZV reactivation is frequently associated with the use of ATO in patients with APL. Clinicians should be aware of the high incidence of VZV reactivation during ATO treatment, and should provide information to patients about the risk of VZV reactivation. Combined efforts and close collaboration of clinicians and patients are necessary for early diagnosis and prevention of this important complication." @default.
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• W2003177761 date "2013-09-24" @default.
• W2003177761 modified "2023-09-27" @default.
• W2003177761 title "High Frequency of Varicella Zoster Virus Reactivation Associated with the Use of Arsenic Trioxide in Patients with Acute Promyelocytic Leukemia" @default.
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• W2003177761 doi "https://doi.org/10.1159/000353126" @default.
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