Immune Reconstitution & Vaccine Response After Pediatric Allo-HSCT

Background: Transfer of donor immunity for vaccine preventable diseases in allo-HSCT is limited, requiring re-vaccination after HSCT.  The CDC 2009 guidelines introduced changes, including earlier vaccination post-HSCT with a uniform vaccination strategy irrespective of transplant variables. The CDC guidelines acknowledge vaccination response varies, but significant knowledge gaps exist regarding factors affecting immune recovery and response to vaccination post-HSCT. The objective of this study is to describe predictors of immune recovery and adequate response to vaccination 1 year post-HSCT.

Methods: We conducted a retrospective chart review of all pediatric allo-HSCT patients transplanted between July 1, 2007 through June 30, 2012 who survived >1 year post-transplant without relapse (N=27). For evaluation of vaccine response, 8 patients were excluded (5 with incomplete data/refused vaccines, 2 with cGVHD, 1 receiving IVIG). Adequate response to vaccination was defined as a > 4-fold increase in tetanus titers >1 month after vaccination.  Wilcoxon Rank-Sum Exact test and Kruskall-Wallis tests were used to analyze CD4, CD8, and CD19 counts with a type 1 error rate fixed at 0.05.  Exact conditional logistic regression was utilized to analyze adequate vaccination response 1 year post-HSCT. 

Results: Overall, a statistically significant increase in median CD4, CD8, and CD19 counts was seen from 6 to 12 months post-HSCT (p= <0.0001, 0.005, 0.004).  Patients with aGVHD or cGVHD, however, lacked a significant increase in cell counts.  Among graft sources, CBU recipients had the highest median cell counts.  Among preparative regimens, patients with RIC had the lowest median cell counts. Only 36% of patients had adequate vaccination response at 1 yr post-HSCT.  For the remaining evaluable patients, 88% required one and 12% required two additional re-vaccination attempts. None of the variables tested (graft source, preparative regimen, disease status, ATG/alemtuzumab, GVHD prophylaxis, cell counts, GVHD) were statistically significant in predicting adequate vaccine response.

Conclusions: There was no association between predictors of immune recovery or transplant variables and vaccination response in this study.  A uniform vaccination strategy is unlikely to provide protective antibodies for many post-HSCT patients and should be evaluated in larger studies.