Varicella zoster reactivation after hematopoietic stem cell transplant in children is strongly correlated with leukemia treatment and suppression of host T-lymphocyte immunity.
OBJECTIVE
Varicella zoster virus (VZV) reactivation following hematopoietic stem cell transplantation (HSCT) may cause significant morbidity and mortality. We undertook a retrospective study to determine the frequency and risk factors associated with VZV reactivation, including underlying disease, the use of fludarabine in high-risk leukemia chemotherapy protocols, and immune status before HSCT.


METHODS
We studied 163 children who underwent a first HSCT between 2002 and 2008, before introduction of routine VZV prophylaxis on our unit. VZV diagnosis was based on clinical features and supported by polymerase chain reaction on plasma and/or vesical fluid. Patient data and possible risk factors pre- and post HSCT were recorded and compared using a multivariate regression analysis.


RESULTS
Within this cohort, 41 (25%) patients developed VZV reactivation during the first year after transplantation at a median of 60 days post HSCT. VZV reactivation occurred more often within the subgroup of patients with acute leukemia compared with the remainder of patients (38% vs. 15%, P < 0.01). Multivariate Cox regression analysis revealed that, besides positive VZV serology in patients pre-HSCT (P = 0.03), acute leukemia as the indication for HSCT remained the only independent risk factor for VZV reactivation (P = 0.025, odds ratio 2.5, 95% confidence interval 1.1-5.6). This was associated with low pre-transplant T-cell counts, especially in the CD4(+) subset. No differences were found in relation to donor type, age, or use of serotherapy.


CONCLUSIONS
VZV reactivation after HSCT predominates in acute leukemia patients and is associated with low T CD4(+) lymphocyte counts. This finding demonstrates the impact of pre-HSCT host immune suppression on VZV reactivation patterns after HSCT.
Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
C L
CL
Vermont
E C M
EC
Jol-van der Zijde
P
P
Hissink Muller
L M
LM
Ball
R G M
RG
Bredius
A C
AC
Vossen
A C
AC
Lankester
D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D014645:Herpesvirus 3, Human / Q000502:physiology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives*; D014775:Virus Activation / Q000276:immunology*; D055815:Young Adult
D000970:Antineoplastic Agents; D014740:Vidarabine; C024352:fludarabine
hematopoietic stem cell transplantation; pediatric; varicella zoster virus; viral reactivation