Vaccinations Efficacy in Long Term Survivors After Allogeneic Stem Cell Transplantation: Implication of Repeat Vaccinations and Documenting Vaccination Efficacy.

With improvements in transplant techniques,more patients now survive free of disease for which they are transplanted. Vaccine preventable infections remain a significant cause of morbidity, re-hospitalization and mortality after successful allogeneic stem cell transplantation (allo-SCT). Although infections are highest in patients with chronic graft versus host disease (cGVHD), incidence in patients without cGVHD post- transplant is over 20 times that reported in general population. Current literature on vaccine efficacy following allo- SCT has often been limited by lack of long term follow-up.

To determine the response of vaccinations in patients surviving beyond 3 years post transplant, post- vaccination titers were analyzed in an institutional review board approved study. Patients received routine post- transplant vaccinations as recommend in CDC guidelines (MMWR Recomm Rep 49:1–125, CE1–7, 2000). Immunological responses to vaccinations were defined by standard criteria with positive antibody titers. We selected 3 year minimum follow-up as most patients are expected to be in remission and have achieved minimal milestones of immune competence.

Study evaluated the response of post- transplant vaccination (Hepatitis B, Td, Hib, and PPV23) in 22 (male=13) long term survivors after allo- SCT. All patients are alive after median follow-up of 59 months (range, 41-108). Median age at transplantation was 44 years (range, 20 to 60). The indication for SCT was AML/ MDS (7), ALL (5), CML (5), and other hematological malignancies in 5 patients. Seventeen (77%) patients received a myeloablative conditioning (TBI=11, non-TBI=6) and 5 (23%) patients received a non-myeloablative regimen followed by matched related (n=16) or unrelated donor allo-SCT (n=6). GVHD prophylaxis consisted of cyclosporine or tacrolimus and methotraxate (n=19) or mycophenolate (n=3). Only one patient received in-vivo T-cell depletion with thymoglobulin. Acute GVHD (aGVHD), grade II-IV occurred in 19 (86%) patients and chronic GVHD in 18 (81%), classic chronic =14, overlap=4; nine (40%) patients had ≥3 organs involvement. Ten (45%) patients were receiving low dose immunosuppressive therapy (IST) for chronic GVHD at the time of analysis. IgG level at the time of vaccination was available in 20 (91%) patients (median level 704 mg/dl). Sixteen (80%) patients had IgG level of ≥490 mg/dl. Immune response after vaccinations summarized in Table 1. Median time to vaccination titers check after allo- SCT was 55 months (range 36-104 months). There was no serious adverse reaction in any patients attributed to vaccinations. Significantly poor vaccination response was seen with pneumococcal vaccine (PPV23) as compared to others (P<0.0001). This correlated with an increased risk of recurrent bacterial infections in long- term survivors. Risk factor analysis showed, no impact of age, type of SCT, GVHD, IgG level, time to titers post- vaccination, follow-up duration post- SCT on vaccination response.

Our data emphasized that unlike immunization of healthy individuals, vaccination post- SCT does not ensure seroprotection, even in patients who have achieved limited immune milestones, stressing the need to document post- vaccine titers to determine response. Prospective, multicenter trials assessing the best strategy for administration of post- transplant vaccination and its impact on infectious complications following transplantation are warranted. In view of poor response to current vaccination, immunization of donor and host prior to transplantation and role of conjugate (highly immunogenic) vaccines also need to be explored in controlled trials.

Jagasia:Genzyme: Research Funding.