Impaired Antibody RESPONSE FOLLOWING VACCINATION Against Hepatitis-B VIRUS In Autografted PATIENTS for Hematologic Malignancies: PRELIMINARY RESULTS
Authors: Kaloyannidis Panayotis , Konstantinou Varnavas , Georgiadou Elisavet , Zervou Fani , Batsis Ioannis , Mallouri Despina , Yannaki Evangelia , Papathanasiou Maria , Xoheli Aliki , Sakellari Ioanna , Kiriazis George , Anagnostopoulos Achilles 
Published: October 2019

Abstract
Abstract 1999
Infections are major barriers for a favorable outcome following stem cell transplantation (SCT) and their prevention is a significant task in the clinical practice. Vaccinations are well established strategies to reduce the risk of vaccine-preventable infection after SCT. The effectiveness of timely vaccination is subject to many factors including the patient's immune reconstitution. Consequently, the response to vaccination may also be an indirect marker for assessing immune function. Although some reports have demonstrated that the type of transplant may affect the response to vaccines, the European Group for Blood and Marrow Transplantation (EBMT), for practical reasons, recommends identical vaccination programs for allo- and auto SCT. Hepatitis B virus (HBV) can cause severe and sometimes fatal hepatitis after SCT and therefore all anti-HBs negative transplant recipients should receive vaccination against HBV post SCT. Although very limited published data exist, the general aspect is that the immune system rapidly recovers following autoSCT and so far, autografted patients are considered to have similar antibody response to healthy individuals. The vaccination programs for HBV in healthy population are: i) three doses at 0, 1, and 6 months, or ii) four doses at 0, 1, 2 and 12 months for high risk individuals. The reported response rate is 15% after the 1st and 80–89% after the 2nd dose. The EBMT recommends 3 doses (0, 1, and 6 months) for both auto and allo recipients. In this study we evaluated the anti-HBs response of 36 autografted recipients for hematologic malignancies, vaccinated against HBV with a recombinant DNA vaccine (EngerixÒ20mcgr, GlaxoSmithKline). All patients achieved or maintained complete response (CR), and received no other therapy after SCT. Their median age was 34(14–55) years and they had received 2(2–7) lines of chemotherapy prior to SCT. BEAM was the conditioning regimen for the majority of the patients (26/36). No patient was immunized for HBV prior to SCT. The median interval from the time of transplant to the first dose of the vaccine was 5.5 (2–20.5) years. The median CD34+ and CD3+ infused cells were 4.5×106/kg and 1.96×108/kg, respectively. The engraftment was successful and the reconstitution (cells >500/mm3) for neutrophils was observed at day +11 while for lymphocytes at day +15. After day +100 the median counts of CD4+, CD8+, NK and B lymphocytes were 287, 909, 273 and 154/ml, respectively. According to our study's vaccination schedule, patients who achieved protective (>10mIU/ml) anti-HBs titers after the 2nd dose received the 3rd dose at 6 months (0, 1 and 6 months schedule) while the non-responders received two more doses (0, 1, 2 and 12 months schedule). After the 1st dose only 1/36 patients (3%) had protective response. This percentage reached to 17% after the 2nd dose (5/30 evaluated patients). Seven of nine (77%) patients, developed >10 IU/l anti-HBs titers after the 3rd dose. In a univariate (t-test) and multivariate (logistic regression) analysis the following factors were evaluated: sex, age, lines of therapies, number of infused CD34+ and CD3+ cells, time to engraftment for neutrophils and lymphocytes and the interval from SCT to vaccination. No factor was proven to be significant in terms of achieving protective anti-HBs titers after the 2nd dose of vaccination, probably due to the number of evaluated patients. According to the published data, this ongoing study represents the largest series of patients post autoSCT studied for anti-HBs response after vaccination against HBV. The low response rates we observed following the 2nd dose (only 17% vs. 80–89% that has been reported for healthy people) may suggest that autografted patients possibly have a long lasting immune impairment and hence an intensified vaccination program is needed for this group of patients. Undoubtedly, definitive conclusions will be drawn from studies with larger series of patients.

Disclosures:
No relevant conflicts of interest to declare.