Vaccine Responses Following Unrelated Double Cord Blood Transplantation (CBT)

Background: CBT recipients may respond to post-transplant vaccines differently than other transplant groups due to the lack of transfer of donor immunity. Methods: We analyzed vaccine responses in 48 CBT recipients transplanted at our center from 2005-2010 for the treatment of hematologic malignancies with myeloablative or non-myeloablative conditioning. GHVD ppx included a calcineurin-inhibitor and MMF. All patients received double unit CB grafts and no pt received ATG.  Vaccination criteria included CD4+ cell count > 200 cells/ul and IgG level > 500 mg/dl at > 6 weeks following the last IVIG dose. Results: Forty-eight of 69 (70%) eligible pts alive & disease-free @ 12 months post-HCT were vaccinated. Vaccinated patients engrafted with 6/6 (n = 2), 5/6 (n = 26), or 4/6 (n = 20) HLA-matched units. Twelve pts received rituximab (median 4 doses) as planned peri-transplant therapy for B-cell malignancies (n = 6), EBV viremia/ lymphoma (n = 3), autoimmune hemolysis (n = 1), pure red cell aplasia (n = 1), or recurrent disease (n=1). Prior to immunization, 13 patients had no acute or chronic GVHD whereas 35 had prior grade II-IV acute and/or chronic GHVD. Overall, the median time to vaccination was 16.9 months post-CBT; 18.9 months in pts who received rituximab; 15.23 months in those who did not (p=0.056). Pre-vaccination titers obtained at a median of 1 yr demonstrated that > 85% of patients lacked protection against pneumococcus, H. flu, and pertussis and > 50% lacked immunity against tetanus, measles, & mumps. Seroconversion or > 3- fold rise in titer was observed in > 60% of patients in response to tetanus, diphtheria, H. flu, polio and pneumococcal (PCV7 or PCV13) vaccines. Following 3 doses of rHBV vaccine, 52% pt seroconverted. Only 2/35 recipients of a single Tdap developed protective pertussis titers; 0/8 pts responded to a single protein-conjugated meninogoccal vaccine. To date, 20 pts including 9 adults have received an MMR at a median of 2.3 years post-CBT.  8 pts received the live attenuated varicella vaccine.  To date, seroconversion following measles, mumps, & rubella vaccine occurred in 56%, 41% & 93% of pts, respectively and 5 evaluable pts seroconverted after 1 (n=3) or 2 doses of Varivax (n = 2). Survival in vaccinated patients is 100%.  No serious reactions to any vaccine occurred. Conclusion: CBT recipients, including adults & those with prior GVHD or rituximab therapy, are capable of responding to tetanus, diphtheria, H. flu, polio & PCV7 or PCV13 similar to other transplant groups. The sub-optimal response to pathogens associated with outbreaks in the community (Hepatitis B, Pertussis, meningococcus, measles, mumps, varicella) highlight the need to obtain pre- & post-vaccine titers to document response, and the need to define the optimal vaccination regimen in this population.