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OKA STRAIN LIVE VARICELLA VACCINE IN CHILDREN WITH CANCER

1996; Lippincott Williams & Wilkins; Volume: 15; Issue: 2 Linguagem: Inglês

10.1097/00006454-199602000-00015

1532-0987

Zafer Ecevit, Münevver Büyükpamukçu, G Kanra, Betül Sevınır, Shigeharu Ueda,

Polyomavirus and related diseases

Varicella is a primary infection, occurring in persons with no specific antibody or cell-mediated immunity to varicellazoster virus (VZV). Varicella tends to be a mild disease in otherwise healthy children. However, in immunocompromised individuals the mortality rate and the frequency of serious complications are greatly increased, despite availability of passive immunization and antiviral chemotherapy.1 The predisposition to development of severe varicella results from impairment of cell-mediated immune response to varicella-zoster virus rather than a defect in humoral immunity. A live attenuated varicella vaccine was developed in the early 1970s by Takahashi et al.2 in Japan. Various studies have shown that the vaccine is safe, immunogenic and highly protective in healthy and in certain immunocompromised patients.3-5 In our study we vaccinated children with cancer to determine the immune responses to VZV in vaccinees and the side effects of the vaccine. Materials and methods. Patients selected for vaccination were those attending the Pediatric Oncology Clinic at Hacettepe University Children's Hospital. Informed consent was obtained from the parents after explanation of the study. Twenty-nine children ages 10 months to 16 years (median age, 6.44 ± 4.12 years) with malignancies in remission were immunized with live varicella vaccine. One of the vaccinated children had acute lymphoblastic leukemia; others had different types of solid tumors and other malignancies (8 Wilms' tumor, 5 neuroblastoma, 4 non-Hodgkin's lymphoma, 3 Hodgkin's disease, 2 Ewing's tumor, 1 nasopharyngeal carcinoma, 1 giant cell granuloma, 1 eosinophilic granuloma, 1 rhabdomyosarcoma, 1 malignant fibrous histiocytoma and 1 child with hamartoma). All had no history of varicella or zoster. Twenty-two patients were vaccinated while receiving maintenance chemotherapy; the median time of chemotherapy was 13.95 ± 7.49 months (range 4 to 30 months). In these cases maintenance chemotherapy was suspended for 1 week before and 1 week after immunization. The remaining 7 children had completed chemotherapy before receiving the vaccine; the median time after completion of chemotherapy was 9 ± 5.19 months (range, 3 to 18 months). An additional prerequisite for varicella vaccination was a peripheral blood lymphocyte count of at least 1.2 × 109/l. All of the children were immunized with the same lyophilized lot of live attenuated Oka strain varicella vaccine Biken, produced by Biken Institute, Osaka, Japan. Immediately before use the contents of each vaccine vial was freshly reconstituted with 0.5 ml of sterile water for each dose and injected subcutaneously, in the left or right deltoid area. One dose (0.5 ml) of vaccine contained no fewer than 1000 plaque-forming units of the Oka strain varicella virus. Patients were vaccinated with a two-dose regimen, 1 month apart. Serum samples were taken before administration of the first dose of vaccine and 1 month after the second dose. Serum samples before and after vaccination were tested for antibodies against VZV by fluorescent antibody to membrane antigen assay.6 Antibody assay were done at Kan-onji Institute, Research Foundation for Microbial Diseases of Osaka University, Handai Biken Foundation. The reactogenicity of the Oka strain vaccine was assessed by instructing the parents of vaccinated children to record all signs of systemic or local reactions of the vaccination to 8 weeks after the second vaccination. If a rash or other evidence of illness developed in the vaccinee or other family members, patients were checked by the medical staff. Results. A total of 29 children (14 girls and 15 boys) with a negative varicella history were vaccinated. Twenty vaccinees had varicella-zoster fluorescent antibody to membrane antigen titers of <1:4 before immunization. Low antibody titers were present before vaccination in 9 patients (in 8 patients range 1:16 to 1:32, in 1 patient 1:128). One seronegative and two seropositive vaccinees did not return for follow-up. The antibody titers after vaccination have shown considerable individual variation, ranging from 8 to 128 or more (median, 49.53 ± 36.90). Seroconversion after immunization was observed in 18 (95%) seronegative patients (Table 1). On the other hand in 3 of 7 seropositive patients, an antibody rise was noted. There was no difference in response as related to length of time receiving maintenance chemotherapy or length of time after chemotherapy was discontinued. There were no severe side effects of vaccination. Mild clinical reactions were observed in 8 of 29 (28%) children. Maculopapular or papulovesicular rashes occurred after the first dose in 5 (17%) children and after the second dose in 7 (24%) children. The rashes were not severe and extensive (number of rashes, 10 to 100; median, 30). Six children had temperatures as high as 40°C, lasting for up to 3 days, associated with rash. No local reaction was observed at the injection site. In the families of vaccinees there was no clinical evidence of spread of VZV from the vaccinee to susceptible siblings or other family members. No case of herpes zoster occurred. Discussion. Without active or passive immunization, disseminated disease develops in about 30% of children with an underlying malignant condition who contract varicella, with a case-fatality rate of at least 7%.7 Varicella vaccine might prevent death and complications in immunocompromised patients. Routine varicella vaccination programs for healthy children could prevent 94% of potential cases, provided that the vaccination coverage rate is 97% at school entry and routine vaccination is cost-effective.8 Most attention with varicella vaccine has been paid to leukemic patients in studies of immunocompromised children.4, 5, 9 There have been few clinical trails in malignancies other than leukemia, such as in patients with solid tumor.7, 10-12 The total number of patients with solid tumors included in previous clinical studies approximates 100. Gershon et al.5 found a seroconversion rate of approximately 80% in leukemic children by fluorescent antibody to membrane antigen after 1000-plaque-forming unit doses of Oka strain varicella vaccine. Heller et al.10 vaccinated 19 children with acute lymphoblastic leukemia or other malignancies. Conversion rates for circulating VZV antibody, measured at 4 to 6 weeks after vaccination by an immunofluorescence test and an enzyme-linked immunosorbent assay, were 67 and 28%, respectively. In our study VZV antibody conversion rates were high. Haas et al.1 vaccinated 26 patients with acute lymphoblastic leukemia and other malignancies and found a seroconversion rate of 94% in seronegative patients; in this series as in that of Heller et al.10 the majority of patients had acute acute lymphoblastic leukemia. Health et al.12 found that seroconversion rates were 62% after 1 dose regimen in 39 children with various malignancies. No severe side effect were noted, mild to moderate rashes that followed immunization were not a significant problem for the vaccinees. Children with vaccine-associated rash are at risk of transmitting the infection to other varicella-susceptible persons.5, 13 The rate of transmission of the virus from a vaccinee with rash to susceptible household contacts was 17%,14 but there was no spread of the vaccine type virus to contacts if the vaccinee had no skin rash.5 We suggest that immunocompromised children should receive the live varicella vaccine during a short interrupted period of maintenance chemotherapy. Zafer Ecevit, M.D.; Münevver Büyükpamukçu, M.D.; Güler Kanra, M.D.; Betül Sevinir, M.D.; Shigeharu Ueda, M.D. Pediatric Infectious Disease (ZE, GK) and Pediatric Oncology (MB, BS) Units Hacettepe University School of Medicine Ankara, Turkey Research Institute for Microbial Diseases Department of Neurovirology Osaka University Osaka, Japan (SU)