ABSTRACT
Introduction: In winter, mortality in the elderly general population is increased. Among other causes, this is due to infections from seasonal respiratory viruses and pneumonia. Patients afer hematopoietic stem cell transplantation (HSCT) frequently experience such infections. We therefore hypothesized that HSCT recipients experience excess mortality during winter. Method(s): This is a retrospective cohort study using the SBST database to assess the proportion of HSCT-patients who died during winter defned as from October to March as compared to the summer half of the year. Histograms depict distribution of dates of death. Univariate analyses for death afer allogeneic and autologous HSCT of factors potentially associated with higher risks of winter deaths such as patient age, disease, disease stage, presence of GvHD and treatment center were done by chi-squared tests. Multivariable logistic regression was done separately for all patients and those surviving less and more than 100 days and more than one year to separately evaluate early and late deaths. Result(s): Between 1997 and 2019 12'412 patients received HSCT (8107 auto, 4305 allo). 4904 patients died (3218 auto, 1686 allo). Overall, 2517 patients (51.3%) of those died in the winter season, 2387 (48.7%) in summer (fgure 1). The proportion of patients with deaths in winter did not difer by type of HSCT, age, disease or disease stage at the time of transplant. Excluding patients dying in the first 100 days and in the first year afer transplant or those dying without relapsed disease did not change these results. Only deaths in the first 100 days afer autologous HSCT had a higher number of events in winter but this did not reach statistical signifcance (p=0.17). Of particular interest, in patients afer allogeneic HSCT the proportion of deaths occurring in winter was 48%, 49%, 52% and 51% in patients with a transplant age less than 20, 20-40, 40-65 and >65 (p=0.61). Conclusion(s): Contrary to our assumption, no higher mortality in winter was found in HSCT patients pointing to no increased death rate due to respiratory viruses. Additional data will be analyzed once the Covid-19 pandemic is over. [Figure Presented].
ABSTRACT
Background: Induction of immunological tolerance has been the holy grail of transplantation immunology for decades. The only successful approach in the clinical situation has been a combined kidney and hemato-poietic stem cell transplantation from the same living donor. Here, we report the first three patients included in this first European trial to induce tolerance by mixed lymphohematopoietic chimerism. Methods: The protocol followed previous studies at Stanford University: kidney transplantation was performed on day 0 including induction with anti-thymocyte globulin followed by conditioning with 10x1.2 Gy total lymphoid irradiation and the transfusion of CD34+ stem cells together with a body weight-adjusted dose of donor T cells. Immunosuppression consisted of cyclosporin and steroids for 10 days, cyclosporin and mycofenolate mofetil for 1 month, and then cyclosporin monotherapy with tapering over 9-20 months. Results: Two female and one male patients were transplanted with a kidney and peripherally mobilized hematopoietic stem cells from their HLA-identical sibling donor. No rejection or graft-versus-host disease occurred in these patients, which are currently off immunosuppression since 31, 18 and 6 months. Chimerism was stable in the first, but slowly declining in the other two patients. A molecular microscope analysis in patient 2 revealed the genetic profile of a normal kidney. No relevant infections were observed, and the quality of life in all three patients is excellent. During the SARS-CoV2 pandemic, all three patients were vaccinated with the mRNA vaccine, and they showed excellent humoral and cellular SARS-CoV2-specific immunity. Conclusions: Combined kidney and hematopoietic stem cell transplantation is a feasible and successful approach to induce specific immuno-logical tolerance in the setting of HLA-matched living kidney donation while maintaining immune responsiveness to a viral vaccine.