Lymphoid neoplasms are among the most common hematologic malignancies. Viral infections are important causes of mortality and morbidity in patients with lymphoma. The majority of viral infectious complications in these patients result from the reactivation of various viruses such as Herpes Zoster (HZ). Most cases of HZ are self-limited; however, immunocompromised patients have a higher mortality rate from HZ and are at greater risk for recurrences and more serious and atypical complications.
The most important established risk factors for developing HZ in cancer patients include neutropenia, duration and intensity of treatment, type of chemotherapy received, comorbid conditions such as Diabetes Mellitus, being recipient of a stem cell transplant, among others. However, the impact of baseline laboratory characteristics such as absolute lymphocyte count (ALC) and lactate dehydrogenase (LDH) as well as the cell type and stage of lymphoma at diagnosis on the risk of developing HZ remains unclear.
Anecdotal data suggest that prophylaxis with acyclovir might be beneficial to decrease the incidence of HZ among patients with lymphoma receiving chemotherapy. Although it is well known that the two FDA-approved HZ vaccines decrease the incidence of this condition in immunocompetent hosts, the Advisory Committee on Immunization Practices has not made recommendations regarding its use in immunocompromised patients. In view of the debilitating condition of lymphoma patients and the unclear effectiveness of anti-HZ vaccine in this disorder, it seems urgent to find better preventive and treatment strategies.
Materials and methods
We conducted a retrospective cohort study of patients diagnosed with lymphoma registered in the database of Auxilio Mutuo Cancer Center (AMCC). Our study analyzed the incidence of HZ in patients diagnosed with lymphoma at any time during the course of illness. The duration of this study was from 1997-2017. The variables were the following: gender, age >50 at diagnosis, type of chemotherapy, having diabetes mellitus, having received an autologous stem cell transplant (ASCT), multiple courses of chemotherapy, radiotherapy, rituximab, or what we labeled as "highly immunosuppressive chemotherapy (HIC)", date of relapse or death, stage at diagnosis, indolent or aggressive presentation, baseline LDH, baseline ALC<1000, and date of HZ. The frequencies of each categorical variable were compared with chi-square tests (χ2 test) or Fisher's exact tests. All statistical analyses were based on two-sided hypothesis tests with a significance level of P< 0.05.
From 1997-2017 there were 414 lymphoma patients with median age at diagnosis of 53 years. There were 90 patients with HD, 6 patients with NK/T-cell lymphoma, and 319 with NHL. During a median follow up of 10 years a total of 46 HZ cases were identified for an overall incidence density of 11.2%. Higher rates of HZ were associated with the following factors: multiple courses of chemotherapy (p=0.035), indolent lymphoma (p=0.012), advanced stage at diagnosis (p=0.034), having received HIC (p<0.001), and having lymphopenia at the time of diagnosis (p=0.038). The other variables studied did not exhibit higher rates of HZ.
Our study is one of the first to estimate incidence rates of HZ and examine risk factors and complications of HZ in lymphoma patients according to specific histologic subtype and presentation. The overall incidence among all groups was significantly higher than in the general population. We have documented that HZ incidence varies with treatment regimens and stage of disease at diagnosis as well as presentation of indolent vs aggressive. Lymphocytopenia was not described previously in the literature as a risk factor for developing HZ but in our cohort patients having ALC<1000 at diagnosis displayed a significantly higher incidence of HZ. The patients who received multiple courses of chemotherapy and HIC also exhibited significantly elevated risks for HZ. Because the overall incidence of HZ was higher among the patients with lymphoma during chemotherapy, prophylaxes against HZmight be considered, particularly for patients with the risk factors. However, optimal duration and preferred regimen for prophylaxis remain to be elucidated.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.