Cellular Immunity to Vaccinations and Herpesvirus Infections After Bone Marrow Transplantation

104

Summary:We report a retrospective analysis of VZV infection after haematopoietic stem cell transplantation (HSCT) in children. Thirty-three (30%) of the total 109 children who were transplanted during a 7 year period developed post-transplant VZV infection. Twenty-four of these 33 (73%) children had VZV infection within 1 year following HSCT. The cumulative incidences of post-transplant VZV infection at 1 and 5 years were 26% and 45%, respectively. The positive and negative predictive values of pretransplant VZV serology in recipients on the development of HZ following HSCT were 39% and 88%, respectively. Pretransplant VZV seropositivity in recipients was the only risk factor for post-transplant herpes zoster (HZ) infection on multivariate analysis. All patients responded to acyclovir. The median duration of VZV infection was 5 days. Three (11%) and one (3%) children with HZ developed visceral dissemination and post-herpetic neuralgia, respectively. No mortality was directly attributed to VZV infection. VZV infection remains a major cause of morbidity in children after HSCT. Further studies are warranted to evaluate the potential use of VZV vaccine in these children. Bone Marrow Transplantation (2000) 25, 167-172. Keywords: haematopoietic stem cell transplantation; herpes zoster; paediatric; varicella-zoster virus Varicella-zoster virus (VZV) is a herpes virus that causes chickenpox (CP) as a primary infection and herpes zoster (HZ) when the latent virus is reactivated. It is a significant cause of morbidity and mortality in immunocompromised patients. Ten percent of children with leukaemia on maintenance chemotherapy died of VZV infection in the preacyclovir era. 1 Haematopoietic stem cell transplantation (HSCT) is now the treatment of choice for some malignant and nonmalignant conditions in children. However, these patients are at high risk of having severe VZV infection because of significant and prolonged immunosuppression in the post-transplant period. The incidence of VZV infec- tion in children following HSCT varied from 23% to 67%. [2][3][4][5][6] Herpes zoster is one of the common late infections in post-transplant patients. The median onset of HZ following HSCT occurred at the fifth month. 7 However, risk factors for post-transplant VZV infection in children are less well defined because there are few reports on this subject. In this study, we review the incidence, risk factors, treatment and clinical outcome of VZV infection in children who underwent HSCT at our centre. Patients and methods Study population and design

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Incidence, risk factors and outcome of varicella-zoster virus infection in children after haematopoietic stem cell transplantation

Leung

Chik

et al. 2000

104

“…Following allogeneic SCT mature donor CD19 + B cells can provide sustained antibody production upon reimmunization or reinfection. 1,2 Crucial to the immunological function after transplantation is the reconstitution of an antigen specific T cell compartment required for effective cellular immunity and the support of specific antibody production by B cells. In young patients with intact thymic function the T cell compartment is primarily regenerated by HSCs of donor origin.…”

mentioning

confidence: 99%

Flow cytometric assessment of lymphocyte subsets, lymphoid progenitors, and hematopoietic stem cells in allogeneic stem cell grafts

Theilgaard‐Mönch

Raaschou‐Jensen

Palm

et al. 2001

Summary:Currently, bone marrow (BM), cord blood (CB), and G-CSF-mobilized peripheral blood progenitor cells (PBPCs) are the most commonly used sources for allogeneic stem cell transplantation (SCT). The aim of this study was to assess the yields and distribution of lymphocyte subsets, lymphocyte progenitors and hematopoietic stem cells (HSC) in each type of allograft by threecolor flow cytometry. high T cells were highest in CB grafts (P р 0.001), and higher in LPs than in BM grafts (P р 0.02). The latter finding was in accordance with a preferential G-CSF mobilization of naive T cells relative to the total lymphocyte population (P р 0.014). CD3 + CD8 low and CD3 + CD8 low CD4 − subsets, which facilitate engraftment in murine transplantation models, demonstrated a tendency towards lower frequencies among T cells in CB grafts and LPs compared to BM grafts. This observation coincided with a significantly reduced mobilization of subsets potentially enriched for facilitating cells as compared to the total lymphocyte population (P р 0.036). The CD34 + compartment of CB grafts contained a significantly higher percentage (12.1%) of CD34 + CD7 + CD3 − T cell progenitors than those of BM grafts (5.1%) and LPs (3.6%). In addition, CB lymphocytes contained the highest fraction of CD3 − CD16/56

“…26 Whether this inadequate response was the result of early vaccination or the presence of chronic GVHD is unknown because the other studies have employed late vaccination. Multiple doses of diphtheria toxoid 2-6 years after allogeneic BMT resulted in adequate immune response in thalassemia patients without chronic GVHD.…”

Section: Diphtheria Toxoidmentioning

confidence: 99%

Reimmunization after blood or marrow stem cell transplantation

Singhal

Mehta

1999

Summary:Protective immunity to diseases preventable by routine vaccination is lost over time following allogeneic and autologous blood and marrow transplantation. Adoptive transfer of immunity from donors to recipients after allogeneic transplantation is not sufficient to prevent this decline. Systematic reimmunization is necessary at appropriate time intervals following transplantation to re-establish immunity. Response to vaccination depends upon the type of transplant, the source of cells, the immune status of the patient, and the vaccine being used. While inactivated or subunit vaccines are safe in all transplant recipients, live vaccines are generally contraindicated. Reimmunization practices vary widely amongst transplant centers. This comprehensive review summarizes published data on post-transplant vaccination, and based upon these, suggests guidelines which may be used as a framework for development of reimmunization protocols. Keywords: allogeneic bone marrow transplantation; autologous bone marrow transplantation; hematopoietic stem cell transplantation; immunization; vaccination Passive immunization consists of the administration of antibody-containing immunoglobulin preparations to provide temporary protection. Active immunization refers to the administration of a vaccine or a toxoid and is analogous to vaccination. 1 Vaccines available for routine use in children include diphtheria-pertussis-tetanus (DPT), trivalent polio, measles-mumps-rubella (MMR), Haemophilus influenzae type b (Hib), hepatitis B and tuberculosis (BCG). Adult vaccines include diphtheria-tetanus (DT), hepatitis B, influenza virus and pneumococcus. The use of meningococcal, hepatitis A and varicella vaccines is increasing. A number of other vaccines are also available for special circumstances. 1 Most allogeneic and a large proportion of autologous bone marrow transplant recipients lose their immunity to poliovirus, tetanus, diphtheria and measles after transplantation. 2 risk of developing infections with organisms such as H. influenzae and Streptococcus pneumoniae for which vaccines are available. 9-11 Because of these reasons, it is essential to reimmunize peripheral blood stem cell (PBSCT) or bone marrow transplant (BMT) recipients at appropriate times following transplantation. 12-14 Current practiceSystematic post-transplant reimmunization is a relatively neglected area. 12,14 A survey of reimmunization protocols in Europe found wide variations in practice. 12 Tetanus toxoid vaccination was the most common practice, with 65% of the surveyed centers administering this to allograft recipients, and 37% to autograft recipients. On the other hand, pertussis vaccination was the least common practice, with only one center using this. 12 A survey of 45 North American transplant centers affiliated with the National Marrow Donor Program 14 showed that 97% of centers allografting patients under the age of 7 years and 88% of those allografting patients aged 7 years or older gave either the DPT or the DT vaccine, whereas 77% and 58%, res...