Monoclonal gammopathy after intense induction immunosuppression in renal transplant patients

Objectives. Incidence and risk factors of post-transplant monoclonal gammopathy were studied in renal transplant patients who received their grafts between 1982 and 1992 (n=390 grafts). Immunoelectrophoresis was performed at annual intervals after transplantation. Results. Forty-six cases of clonal gammopathy were detected: 35 monoclonal, 11 bi- or triclonal, with a predominance of IgG and K light-chain subtypes (IgG, 39; IgA, 3; IgM, 4; K, 35; λ, 19). Gammopathy was transient in 17 patients (37%). The 5-year cumulative incidence of gammopathy was 10.7%, much higher than expected for a group of similar age from the general population. Thirty of the 46 gammopathies appeared within the first 2 years of transplantation. Gammopathy never progressed to multiple myeloma during follow-up (median 1 year; (range 0-10)); one patient subsequently developed Kaposi sarcoma. The 2-year incidence of gammopathy was much higher in patients transplanted in 1989-1991 (23/142) than in 1982-1988 (7/248) (P<0.0001). This coincided with the use of quadruple induction immunosuppression (cyclosporin A+azathioprine+prednisone plus either ATG-Fresenius (ATG-F) or OKT3) since 1989. The risk for acquiring gammopathy within 2 years of transplantation was 14.7% (95% CI 9.2, 20.3%) in patients receiving quadruple induction therapy, but only 3.0% (CI 1.2, 6.1%) without such therapy (P<0.0001). The risk for patients receiving quadruple immunosuppression with OKT3 was 24.5%, significantly greater than with ATG-F (11.8%, P<0.05). Discriminant analysis revealed that the type of immunosuppression, but not age or year of transplantation, were independent risk factors for gammopathy. Conclusions. Monoclonal gammopathy frequently occurs after renal transplantation. Risks are higher for patients receiving quadruple induction immunosuppression, particularly if it includes OKT3. Follow-up of these patients is warranted for the early detection of malignant transformatio

Use of haploidentical stem cell transplantation continues to increase: the 2015 European Society for Blood and Marrow Transplant activity survey report.

Hematopoietic stem cell transplantation (HSCT) is an established procedure for many acquired and congenital disorders of the hematopoietic system. A record number of 42 171 HSCT in 37 626 patients (16 030 allogeneic (43%), 21 596 autologous (57%)) were reported by 655 centers in 48 countries in 2015. Trends include continued growth in transplant activity over the last decade, with the highest percentage increase seen in middle-income countries but the highest absolute growth in the very-high-income countries in Europe. Main indications for HSCT were myeloid malignancies 9413 (25%; 96% allogeneic), lymphoid malignancies 24 304 (67%; 20% allogeneic), solid tumors 1516 (4%; 3% allogeneic) and non-malignant disorders 2208 (6%; 90% allogeneic). Remarkable is the decreasing use of allogeneic HSCT for CLL from 504 patients in 2011 to 255 in 2015, most likely to be due to new drugs. Use of haploidentical donors for allogeneic HSCT continues to grow: 2012 in 2015, a 291% increase since 2005. Growth is seen for all diseases. In AML, haploidentical HSCT increases similarly for patients with advanced disease and for those in CR1. Both marrow and peripheral blood are used as the stem cell source for haploidentical HSCT with higher numbers reported for the latter.Bone Marrow Transplantation advance online publication, 13 March 2017; doi:10.1038/bmt.2017.34

Equal Efficacy of Glucoprotamin and an Aldehyde Product for Environmental Disinfection in a Hematologic Transplant Unit: A Prospective Crossover Trial

Background. The inanimate hospital environment has emerged as an important reservoir of nosocomial pathogens. In particular, multidrug-resistant pathogens, such as methicillin-resistant Staphylococcus aureus, Acinetobacter species, and Clostridium difficile, play a major role in the transmission of hospital-acquired infections. In Europe, aldehydes, chlorine, and quaternary ammonium compounds have been commonly used for environmental disinfection. Glucoprotamin, a newer active compound for disinfectants, has been clinically tested for disinfection of instruments but not for environmental disinfection. Objective. This study evaluated the antimicrobial effectiveness of a glucoprotamin-containing product (Incidin) compared with that of an aldehyde-containing product (Deconex), the current standard at our institution. Methods. This prospective crossover study was conducted in our access-restricted hematologic transplant unit. A total of 3,086 samples from the environment were processed and examined for overall bacterial burden as well as selectively for S. aureus, C. difficile, and gram-negative bacteria. Results. There was no significant difference in residual bacteria after disinfection between the 2 products in terms of overall burden and selected pathogens. Enterococci were the predominant pathogens recovered from surfaces, but no vancomycin-resistant enterococci were recovered. Similarly, C. difficile could not be found in the patients' environment, even in rooms, despite the use of selective media. Conclusion. The aldehyde-containing product (Deconex) and the glucoprotamin-containing product (Incidin) demonstrated similar efficacy against environmental contamination in a hematologic transplant unit with the application of selective media for C. difficile, S. aureus, and gram-negative bacteria in addition to standard mediu

Dissociations of oral foci of infections with infectious complications and survival after haematopoietic stem cell transplantation

Introduction Haematopoietic stem cell transplantation (HSCT) recipients are at increased risk for severe infections. This study examined the associations of common oral infections with survival and infectious complications in HSCT recipients. Materials and methods All autologous and allogeneic HSCT recipients transplanted in the University Hospital of Basel, Switzerland, between 2008 and 2016 and referred to oral infection control pre-HSCT were included in this retrospective case-control study. All patients had a clinical and a panoramic radiological dental examination taken immediately prior to HSCT. Presence of acute or chronic oral foci of infections, decayed, missing or filled tooth index (DMFT) and radiological attachment loss (RAL) were examined. Survival and infections of the subjects were followed up for 6 months post-HSCT. Results Altogether 341 allogeneic and 125 autologous HSCT recipients were included in the study. Within 6 months post-HSCT, 47 (14%) of the allogeneic and 4 (3%) of the autologous recipients died. Oral foci of infections (acute or chronic), DMFT or periodontitis pre-HSCT were not associated with survival 6 months post-HSCT. Oral foci of infections were also not associated with hospital treated infectious diseases or blood culture positive bacteremia during the 6 month follow-up period. Untreated oral foci of infections were not associated with survival or severe infectious complications within 6 months post-HSCT. Conclusion The results of this study suggest that radical dental interventions to chronic oral infections could be postponed until post-HSCT.Peer reviewe

Multispecific Aspergillus T Cells Selected by CD137 or CD154 Induce Protective Immune Responses Against the Most Relevant Mold Infections

Background. Aspergillus and Mucorales species cause severe infections in patients after hematopoietic stem cell transplantation (HSCT). Induction of antifungal CD4+ T-helper type 1 (Th1) immunity is an appealing strategy to combat these infections. Immunotherapeutic approaches are so far limited because of a lack of antigens inducing protective T cells, their elaborate production, and the need of targeting a broad spectrum of pathogenic fungi. Methods. We examined the response to different Aspergillus fumigatus proteins in healthy individuals and patients after HSCT and compared rapid selection protocols for fungus-specific T cells based on CD137 or CD154 expression. Results. The A. fumigatus proteins Crf1, Gel1, and Pmp20 induced strong Th1 responses in healthy individuals. T cells specific for these antigens expanded in patients with active invasive aspergillosis, indicating their contribution to infection control. Th1 cells specific for the 3 proteins can be selected with similar specificity within 24 hours, based on CD137 or CD154 expression. These cells recognize naturally processed A. fumigatus and the multispecific T-cell lines, directed against all 3 proteins, especially those selected by CD154, additionally cross-react to different Aspergillus and Mucorales species. Conclusions. These findings may form the basis for adoptive T-cell transfer for prophylaxis or treatment in patients with these devastating infection