Primary vaccination in adult patients after allogeneic hematopoietic stem cell transplantation - A single center retrospective efficacy analysis.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) results in a loss of humoral immunity and subsequent risk for severe infections. Thus, re-vaccination is required but may fail due to incomplete immune reconstitution. We retrospectively analyzed predictors of immune response to primary vaccination applied according to the EBMT (European Blood and Marrow Transplantation Group) recommendations. Serologic response to vaccination against diphtheria (D), tetanus (T), Bordetella pertussis (aP) and Haemophilus influenzae (Hib) (administrated as combined DTaP-Hib-IPV vaccination) was studied in 84 alloHSCT patients transplanted between 2008 and 2015 (age at alloHSCT: 18.6-70.6 years). All patients with a relapse-free survival of ≥9 months, at least 3 consecutive vaccinations and absence of intravenous immunoglobulin administration within 3 months before and after vaccination met the primary inclusion criteria. Additionally, immunological response to a pneumococcal conjugate vaccine was analyzed in a subgroup of 67 patients. Patients' characteristics at the time of first vaccination were recorded. Responses were measured as vaccine-specific antibody titers. Regarding DTaP-Hib-IPV vaccination, 89.3% (n = 75) of all patients achieved protective titers to at least 3 of the 4 vaccine components and were thus considered responders. 10.7% (n = 9) of the patients were classified as non-responders with positive immune response to less than 3 components. Highest response was observed for Hib (97.4%), tetanus (95.2%) and pneumococcal vaccination (83.6%) while only 68.3% responded to vaccination against Bordetella pertussis. Significant risk factors for failure of vaccination response included low B cell counts (p < 0.001; cut-off: 0.05 B cells/nl) and low IgG levels (p = 0.026; mean IgG of responders 816 mg/dl vs. 475 mg/dl of non-responders). Further, a trend was observed that prior cGvHD impairs vaccination response as 88.9% of the non-responders but only 54.7% of the responders had prior cGvHD (p = 0.073). The results demonstrate, that the currently proposed vaccination strategy leads to seroprotection in the majority of alloHSCT patients.

Total nodal irradiation in patients with severe treatment-refractory chronic graft-versus-host disease after allogeneic stem cell transplantation: Response rates and immunomodulatory effects.

BACKGROUND AND PURPOSE: The use of total nodal irradiation (TNI) has been reported as an immunomodulatory therapy for different diseases including chronic graft-versus-host disease (cGVHD). MATERIAL AND METHODS: We retrospectively analyzed 13 patients with treatment-refractory cGVHD receiving TNI with 1×1Gy from 2001 to 2014. In 10 of 13 patients immunomodulatory effects of TNI were measured. RESULTS: At time of TNI all patients had severe cGVHD (involving the skin: n=12), fascia (n=6), oral mucosa (n=8), eye (n=8), and lung (n=5). Nine of 13 patients had corticosteroid-refractory cGVHD. In 7 of 13 patients (54%) a partial response (PR) could be achieved. In 3 patients (23%) cGVHD manifestations remained stable, 2 patients progressed. One patient was not evaluable due to follow-up <1 month. At 3 months after TNI, best responses could be achieved in skin, and oral involvement including steroid sparing activity. TNI was well tolerated with adverse effects limited to reversible thrombocytopenia and neutropenia. Immunomodulatory effects on peripheral blood cells could be demonstrated including an increase of CD4+ T cells in the group of responders. CONCLUSIONS: TNI represents an effective immunomodulating therapy in treatment-refractory cGVHD.