Robust Vaccine Responses in Adult and Pediatric Cord Blood Transplantation Recipients Treated for Hematologic Malignancies

Abstract

As cord blood (CB) lacks memory T- and B-cells, and recent decreases in herd immunity to vaccine preventable diseases in many developed countries have been documented, vaccine responses in CB transplantation (CBT) survivors are of great interest. We analyzed vaccine responses in double-unit CBT recipients transplanted for hematologic malignancies. In 103 vaccine eligible patients, graft-versus-host disease (GVHD) most commonly precluded vaccination. Sixty-five (63%) patients (engrafting units median HLA-allele match 5/8, range 2–7/8) received protein-conjugated vaccines, and 63 (median age 34 years, range 0.9–64) were evaluated for responses. Median vaccination time was 17 months (range 7–45) post-CBT. GVHD (n = 42) and prior rituximab (n = 13) delayed vaccination. Responses to Prevnar 7 and/or 13 vaccines (serotypes 14, 19f, 23f) were seen in children and adults (60% versus 49%, p = 0.555). Responses to tetanus, diphtheria, pertussis, H. influenzae, and polio were observed in children (86–100%) and adults (53–89%) even if patients had prior GVHD or rituximab. CD4+CD45RA+ and CD19+ cell recovery significantly influenced tetanus and polio responses. In a smaller cohort, responses were seen to measles (65%), mumps (50%), and rubella (100%) vaccines. No vaccine side-effects were identified and all vaccinated patients survive (median follow-up 57 months). While GVHD and rituximab can delay vaccination, CBT recipients (including adults and those with prior GVHD) have similar vaccine response rates to adult donor allograft recipients supporting vaccination in CBT recipients.

Optimal Practices in Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies

“…Clinically validated measures of functional immune reconstitution are needed. All patients require post-transplant immunization with all relevant protein conjugate and live vaccines and vaccine responses in CBT recipients have been reported 100 .…”

Untitled

“…Antibody titres in this population decrease over time if re-vaccination was not administered [13]. In double cord blood recipients transplanted for malignancy both children and adults developed responses to Prevnar 7 and or Prevnar 13 pneumococcal vaccines [14]. Our group has previously shown that allogeneic HSCT recipients are deficient in switched and IgM memory B cells [15] irrespective of time post-transplant.…”

Vaccines in pediatric transplant recipients—Past, present, and future

“…Given the distinct characteristics of immune reconstitution following cord blood transplantation, Shah et al. retrospectively reviewed serologic responses to PCVs (either PCV7 or PCV13) in adult and pediatric recipients of umbilical cord HSCT . Serologic response (defined as a >3‐fold rise in titers against serotypes 14, 19F, and 23F) to a 3‐dose vaccine series was evaluable in 15 pediatric patients.…”

“…Two studies have evaluated the response to pertussis vaccination in pediatric allo-HSCT recipients. In a study of umbilical cord HSCT recipients by Shah et al, 100% of pediatric patients demonstrated a pertussis-specific serologic response to a 2-to 3-dose series of Tdap administered a median of 17 months posttransplant 67. However, a separate study by Inaba et al suggests that this successful initial serologic response may not be long-lasting 139.…”