Vaccination against infectious disease following hematopoietic stem cell transplantation

Abstract

Patients undergoing hematopoietic stem cell transplantation (HSCT) experience a prolonged period of dysfunctional immunity associated with an increased risk of bacterial and viral infections. Effective approaches toward vaccinating patients against common pathogens are being explored but are limited by poor levels of responsiveness. Relevant studies examining the nature of reconstitution of cellular and humoral immunity and its impact on vaccination strategies against infectious pathogens are reviewed. Following transplantation, deficiencies in cellular immunity are characterized by the inversion of CD4/CD8 ratios, a decreased proliferative response to mitogens, and the development of anergy to recall antigens as measured by delayed-type hypersensitivity testing. The impact on humoral immunity consists of decreased levels of circulating immunoglobulin, impaired immunoglobulin class switching, and a loss of complexity in immunoglobulin gene rearrangement patterns. In this setting, a loss of protective immunity has been demonstrated against viral and bacterial pathogens previously targeted by childhood vaccination. Infections due to encapsulated bacterial organisms such as Streptococcus pneumoniae and Haemophilus influenzae type B remain prevalent even in the late posttransplantation period. The efficacy of vaccination following HSCT is influenced by the time elapsed since transplantation, the nature of the hematopoietic graft, the use of serial immunization, and the presence of graft-versus-host disease. Strategies to enhance vaccine efficacy include pretransplantation immunization of the stem cell donor and the use of cytokine adjuvants.

Cytotoxic chemotherapy preceding apheresis of peripheral blood progenitor cells can affect the early reconstitution phase of naive T cells after autologous transplantation

“…30 In fact, following HD-ChT, patients are more susceptible to opportunistic infections and to reactivation of persistent virus after transplantation. 7 When we analyzed the prevalence of infectious complications, surprisingly we found that patients with metastatic disease were apparently less vulnerable to VZV reactivation than patients with primary disease. Apparently, such findings would contradict the common observation that patients with advanced disease may have been heavily pretreated with cytotoxic chemotherapy and possibly they may be less immunocompetent than at earlier stage of disease.…”

“…5,6 Consistently, notwithstanding normal WBC values, in the early phase of recovery from HD-ChT, patients are susceptible to opportunistic infections such as Pneumocysti carinii, to endogenous reactivation of varicella zoster virus (VZV), and are not readily eligible for vaccination protocols. 7 Thus, specific approaches to enhance early recovery of CD28+ T cells after HD-ChT are necessary in order to abbreviate T cell immunodeficiency.…”

“…7 Therefore, patients are usually treated with prophylaxis including acyclovir in the first 3 months to reduce the risk of VZV endogenous reactivation. In particular, in our small group of 10 patients studied prospectively for T cell subpopulations after HD-ChT and autologous PBPC transplantation, we could observe typical VZV vesicular skin lesions with a dermatomal distribution in three patients, of whom two had been infused with CTX-PBPC (out of six considered), and one with ET-PBPC (out of four considered).…”

Immune restoration following hematopoietic stem cell transplantation: an evolving target

“…64,65 Such impairment in antibody production has important consequences for revaccination in the HSCT recipient. 66 As delays in IgG2 and IgG4 production may impair T-cell-independent responses to polysaccharide antigens like Streptococcus pneumonia, a leading cause for bacterial infections in the context of GVHD. 67 Similarly, T-cell-dependent antibody production is delayed for at least 1 year after transplantation.…”

Minimal-change nephrotic syndrome in a hematopoietic stem-cell transplant recipient

“…The benefits of vaccination in HSCT recipients are clear (15), and this report should not alter current practice. Because of the expanding indications and growing numbers of HSCTs performed worldwide combined with improved survival, nephrologists need to be familiar with the renal complications of this life-saving procedure.…”