Chicken pox infection in patients undergoing chemotherapy: A retrospective analysis from a tertiary care center in India

Outline

• Summary
• Keywords
• Introduction
• Materials and Methods
• Statistical Analysis
• Diagnosis of Varicella Infection (chicken Pox)
• Therapy and Complications
• Results
• Demographic Details
• Cancer Diagnosis and Treatment Details
• Presenting Symptoms
• Hematologic Parameters at the Time of Varicella Infection
• Complications
• Therapy for the Varicella Infection
• Clinical Course and Recovery
• Effect of Chicken Pox on Cancer-Related Therapy
• Discussion
• Funding
• Competing Interests
• Ethical Approval
• Acknowledgements
• References

Conclusions

In India, most children are exposed to a varicella infection during early childhood [8]. Past clinical or subclinical infections demonstrated by a raised antibody level in the serum, provides protection from future chicken pox infections during periods of immunosuppression [8]. Treating a varicella infection and its complications in pediatric patients with leukemia and those undergoing BMT is a standard practice based on the recommended guidelines [9]. In regard to chicken pox in adult solid tumor malignancies, there are many questions that remain unanswered. We report on 24 patients with chicken pox infections during active chemotherapy. The majority of the patients were adult patients with solid tumor malignancies and our results give some insight into this disease and its impact on the treatment of cancer. Our results also highlight many important aspects of chicken pox infections in solid tumor malignancies, which is scarce in the literature.

The clinical presentation in oncology patients did not seem to differ from those without malignancies. The complication rates were comparable to pediatric malignancies, such as pneumonia, that occurred in 16.5% in our cohort compared with 15—27% that was previously reported in pediatric malignancies [4]. There were no mortalities attributable to chicken pox infection, suggesting that aggressive antiviral therapy and supportive care are essential components for managing these patients.

The severity of disease or delay in recovery from the disease was not significantly different in any particular chemotherapy protocol, and the same is also true for hematological malignancy vs. solid tumor cancers. However, this may be due to the small numbers in our study.

Various factors such as the presence of comorbidities, neutropenia, type of malignancy (solid vs. hematolymphoid) and the age of the patient (adult vs. pediatric) did not appear to have any significant effect on the time taken to recover from a varicella infection. Although the median duration of neutropenia was the same in adults vs. pediatric patients, the median duration of recovery from varicella infection was numerically longer in pediatric patients compared with adults and in neutropenic patients compared with patients without neutropenia; however, these variables did not reach statistical significance. The small numbers in this study preclude any firm comment on these factors being significant.

We found that 70% of our patients had a delay (median of nine days) in chemotherapy as a result of varicella infection. Eighty-three percent of our patients were receiving therapy with the intent to cure. It is widely known that delays in curative treatment can lead to an inferior outcome, as has been studied extensively in breast cancer patients [10]. There is a clear need to prevent chicken pox infections effectively in cancer patients on active chemotherapy to ensure that these patients have the best possible outcome from therapy.

In our cohort, 84% patients had a past recent history of exposure to active chicken pox infection, with three of the patients staying in close proximity to each other. Only two of these 13 had developed childhood clinical chicken pox infection, while the remaining patients probably were unexposed to the varicella virus. Of note, there was no documented epidemic of chicken pox in Mumbai during the period of our analysis. None of the patients’ relatives had received varicella vaccines and no patient was offered prophylactic acyclovir after the diagnosis of chicken pox in the relatives.

As a result of an overall improvement in socioeconomic status, the age of exposure to varicella infections in Indian patients is shifting to the adult age. The varicella infection in an adult is much more severe compared with childhood varicella infections. This fact, combined with the immunosuppression due to chemotherapy for malignancies, probably contributed to the complications and therapy delays in our patients. We need to consider implementing a vaccination program for relatives, even in adult solid tumor cancer patients. There are many recommendations for sibling vaccinations and child vaccination during the maintenance therapy in ALL [11,12], which needs additional consideration in adult solid tumor malignancies. The safety of the chicken pox vaccine in children with hematological malignancies, who are on active chemotherapy, is controversial [13,14]. Nonimmune children with cancer can be effectively vaccinated against chicken pox during the maintenance phase of their acute leukemia treatment or approximately three to six months from treatment discontinuation in those with solid tumors [15]. In clinical trials, transmission of the vaccination version of the virus to immune-compromised contacts from vaccine recipients is not reported, but a possible transmission can occur rarely from vaccine recipients who develop a varicella-like rash [16].

Isolation is another major tool in preventing the spread of infection. We used isolation for the inpatient management of the active chicken pox patients; this strategy likely helped in preventing the spread and possible chicken pox outbreak in our center, which caters to approximately 54,000 cancer patients per year. Isolation of an actively infected chicken pox patient in a negative pressure room is recommended by the American Academy of Pediatrics [17]. If negative air-flow rooms are not available, patients with varicella should be isolated in closed rooms and have no contact with persons without evidence of varicella immunity; patients should only be cared for by staff with varicella immunity. Pediatric oncology units have begun to implement isolation measures after the emergence of reports of chicken pox infection outbreaks in wards [18].

To summarize, the clinical presentation and complication rates of chicken pox in cancer patients who were on active chemotherapy are similar to the normal population. The recovery from a varicella infection and complications may be delayed in patients with neutropenia. The varicella infection causes a therapy delay in 70% of patients. Aggressive antiviral therapy, supportive care and isolation of the index cases remain the backbone of treatment.

Our data had a small number of patients and was a retrospective analysis. Patients were randomly selected and the patient group was heterogeneous, including both adult and pediatric patients with solid tumors or hematolymphoid malignancies. A strength of our analysis includes the fact that it describes the complications of a chicken pox infection in patients with malignancies receiving active therapy. It also discusses the differential effects of neutropenia, tumor type, age of patients and the presence of comorbidities on the patients’ ability to recover from a chicken pox infection. This paper describes the delays in chemotherapy and radiotherapy treatment due to a varicella infection. Most importantly, the inclusion of adult solid tumor patients and the descriptions of their clinical courses and complications when they develop a varicella infection while on active anti-tumor therapy is unique.