Robust Vaccine Responses in Double-Unit Cord Blood Transplantation (CBT) Recipients Despite Lack of Transfer of Memory T and B Cells

Introduction: CBT is now associated with comparable disease-free survival to that of adult donor transplantation. However, given CB grafts lack memory T & B cells, the ability of CBT recipients to respond to vaccines is of great interest. Methods: We analyzed the proportion of surviving double-unit CBT recipients undergoing vaccination & their responses (seroconversion or >3x rise in titers) to primary series vaccines (tetanus, diphtheria, pertussis, H. influenzae, polio & pneumococcus). Pneumococcal response was defined as response to 3 critical serotypes (14, 19f, 23). Patients were transplanted for hematologic malignancies with CNI/MMF prophylaxis between 10/2005-2/2012. Vaccination criteria were ≥1 year post-CBT (earlier in select children), CD4+ >200 cells/ul, & independence from IVIg. Results: Of 132 patients transplanted, 41 died or relapsed prior to 1-year. Of 91 remaining patients, 67 (74%) were vaccinated of whom 63 were evaluable with titer responses. GVHD was the most common reason for survivors not to be vaccinated (18/91, 20%). Median age of 63 evaluable vaccine recipients was 34 years (range 0.9-64); the median time to vaccination was +17 months (range 7-45). Vaccination was delayed in 39 CBTs with prior gr. II-IV acute &/or mod-severe chronic GVHD (+17 months, range 9-45) compared to no significant prior GVHD (+14 months, range 7-33), & in 13 Rituximab (+19 months, range 12-45) recipients. Responses to the primary series vaccines in children < 18 years & adults are shown (Table). Responses were seen even in the setting of prior GVHD or prior Rituximab. Immune function prior to vaccination did not influence responses to pneumococcus, H. influenza, pertussis or diphtheria vaccines. However, those with recovery > median CD4+CD45RA+ (>127/ul) & CD19+ (> 793/ul) counts had increased likelihood of tetanus (p = 0.09 & p = 0.04) & polio (p = 0.05 & p = 0.02) responses. There were no serious vaccine reactions & with a median 54 month (range 22-96) follow-up of vaccinated patients, their survival is 100%. Conclusions: CBT recipients, including adults & those with prior GVHD, are capable of responding to tetanus, diphtheria, pertussis, H. Influenza, polio & pneumococcal conjugate vaccines similar to reported adult donor allograft series. Furthermore, our data suggests improved immune recovery (CD4+45RA+ & CD19+ subsets) prior to vaccination can augment vaccine efficacy. However, GVHD can hinder the ability to commence vaccines in long-term survivors. Additionally, the sub-optimal responses to non-live vaccines in some recipients highlight the need to obtain pre- & post-vaccine titers to document responses, investigate the optimal timing & number of vaccines, & the role of boosters & CD27+ memory B-cell measurement to predict response.

 

Vaccine	Children (n = 18)	Adults (n = 45)
Tetanus	77%	63%
Diphtheria	79%	74%
Pertussis	92%	61%
Haemophilus infl. B	88%	91%
Polio	85%	76%
Pneumococcus	60%	46%