Case Report
Varicella vaccination in a child with acute lymphoblastic

André Schrauder, Cornelia Henke-Gendo, Kathrin Seidemann, Michael Sasse, Gunnar Cario, Anja Moericke, Martin Schrappe, Albert Heim, Armin Wessel Lancet 2007; 369: 1232
In July, 2003, during reinduction treatment 5 months after VZV infection and showed that viraemia was caused by Department of Pediatrics,
diagnosis of acute lymphoblastic leukaemia (ALL), a 4-year- the VZV vaccine strain OKA (fi gure). Vaccination was University Hospital Schleswig-
old girl presented with generalised tonic-clonic seizures. done 5 months after complete remission had been Holstein, Campus Kiel, Kiel,
She had been treated according to protocol ALL-BFM 2000. achieved; at that time lymphocyte count was more than Germany (A Schrauder MD,
Cranial CT and analysis of cerebrospinal fl uid showed no 1·5×10⁹/L, and chemotherapy was interrupted for 1 week M Schrappe MD); and
signs of cerebral haemorrhage. Ultra sonography showed before and after vaccination.
Department of Virology
an enlarged liver and no signs of ascites or veno-occlusive Deaths after vaccinations with numerous attenuated disease. Her skin appeared normal, with no vesicular viruses are well established. Fatal wild-type VZV infections A Heim MD) and Department of
rashes. Blood tests showed only raised concentrations have been reported in ALL patients during chemotherapy2 Pediatric Cardiology
of aminotransferases. During the next few hours, and after bone-marrow cell transplantation.3 Therefore, A Wessel MD), Hannover
VZV vaccination is a useful, and generally accepted, Medical School, Carl-Neuberg-
tomas, and vesicular lesions of the oral and vagi nal therapeutic measure for patients with ALL in remission. Str 1, 30625 Hannover,
mucosal. On the assumption of an underlying infec tious Studies of VZV vaccination 3–4 months after autologous cause, intravenous treatment with piperacillin, sulbactam, stem-cell transplantation,4 and in early ALL maintenance tobramycin, IgG, and aciclovir was initiated. 48 h after the therapy,5 did not show fatal side-eff ects. However, any Henke-Gendo.Cornelia@mh-
fi rst seizure, her laboratory test results deteriorated, with interruption of maintenance therapy in ALL can adversely
aspartate and alanine aminotransferase concentrations aff ect outcome for the patient. In our patient, liver failure increasing to 20 864 U/L and 16 029 U/L, respectively, and developed 5 weeks after VZV vaccination, which indicates the full blood cell count indicated pancytopenia. Within longstanding replication of OKA strain in the liver. This 12 h, she developed multi-organ failure (liver, renal, and suggestion accords with observations of late onset of circulatory failure, and acute respiratory distress syndrome complications (fever, vesicles, and severe hepatitis) in [ARDS]), necessitating artifi cial ventilation. Serostatus for immunocompromised patients after VZV vaccination.5 varicella-zoster virus (VZV) was negative, but PCR for VZV Therefore, although we cannot fully exclude that was positive in peripheral blood samples (7×10⁶ genome intensifi cation of chemotherapy could have aggravated copies per mL). VZV was also isolated from a her symptoms, we suggest that VZV vaccination in nasopharyngeal swab but not from cerebrospinal fl uid. seronegative children with leukaemia, who are in complete PCR analysis of peripheral blood was negative for hepatitis remission for at least 12 months, should not be undertaken B and C viruses, herpes simplex virus 1 and 2, Epstein-Barr until at least 9 months after the end of immunosuppressive virus, cytomegalovirus, adenovirus, enterovirus, human treatment (including maintenance therapy) and not before herpes virus 6, and parvovirus B19. High doses of VZV- a lymphocyte count of at least 1·5×10⁹/L has been IgG were added to the treatment. Despite haemo dialysis ascertained. In addition, high-risk patients should remain and ventilation, the child died of progressive ARDS and under close surveillance in the critical phase (6 weeks after multi-organ failure 10 days after admission.
vaccination) so that immediate antiviral treatment with On receiving the positive VZV-PCR results, the mother aciclovir can be initiated in symptomatic children.
recalled that her daughter had received live attenuated Acknowledgments
VZV vaccine (Varilrix) at another hospital 32 days before
André Schrauder and Cornelia Henke-Gendo contributed equally to the the onset of symptoms. Partial sequencing of VZV genes 38 and 541 isolated from the patient excluded a wild-type References
Sauerbrei A, Wutzler P. Laboratory diagnosis of central nervous system infections caused by herpes viruses. J Clin Virol 2002; 25 (suppl 1): S45–51.
Muller I, Aepinus C, Beck R, Bultmann B, Niethammer D, Klingebiel T. Noncutaneous varicella-zoster virus (VZV) infection with fatal liver failure in a child with acute lymphoblastic leukemia (ALL). Med Pediatr Oncol 2001; 37: 145–47.
David DS, Tegtmeier BR, O’Donnell MR, Paz IB, McCarty TM. Visceral
varicella-zoster after bone marrow transplantation: report of a case
series and review of the literature. Am J Gastroenterol 1998; 93: 810–13.
Figure: Comparison of VZV sequences isolated from the patient with several
Ljungman P, Wang FZ, Nilsson C, Solheim V, Linde A. Vaccination fully sequenced VZV database entries including two VZV OKA vaccine strains
of autologous stem cell transplant recipients with live varicella Two genes (orf38 and orf54) were sequenced and aligned to VZV sequences vaccine: a pilot study. Support Care Cancer 2003; 11: 739–41.
(accession numbers: DQ008354 and X04370) by use of the ClustalW-algorithm. Leung TF, Li CK, Hung EC, et al. Immunogenicity of a two-dose Dots indicate homology to the patient’s sequence.
regime of varicella vaccine in children with cancers. Eur J Haematol
2004; 72: 353–57. Vol 369 April 7, 2007


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