Early Blood Stream Infections after BMT are Associated with Cytokine Dysregulation and Poor Overall Survival

Abstract

The key complications of allogeneic bone marrow transplantation (BMT) remain graft-versus-host disease (GVHD) and opportunistic infection. We have analyzed the blood stream infections (BSIs) occurring between day -7 and day 100 in a cohort of 184 adult patients undergoing allogeneic BMT in our center. A total of 167 of the 184 patients (91%) had blood cultures collected, and 69 (38%) patients had a confirmed BSI. Enterobacteriaceae, Pseudomonas aeruginosa, Enterococcus spp., and viridans Streptococcus spp. were the most commonly isolated organisms. Gender, conditioning (myeloablative versus reduced intensity), and donor type (sibling versus unrelated) did not differ significantly between those with and without confirmed BSI. Elevated temperature (>38°C) at the time of culture collection was associated with an almost 2-fold increased likelihood of returning a positive blood culture. The absence of a BSI was associated with a significant improvement in overall survival at 2 years, due to a significant reduction in nonrelapse mortality predominantly unrelated to the primary BSI. The presence of a BSI before engraftment was associated with the dysregulation of IL-6 and IL-8. Our findings suggest that BSI early after BMT defines a group of high-risk patients with enhanced cytokine dysregulation and poor transplant outcome.

Glucocorticoids inhibit human hematopoietic stem cell differentiation toward a common ILC precursor

“…47,48 According to this model, environmental signals ensure the rapid generation of mature ILCs from a systemic ILCP. Because posttransplantation infections have been associated to increased levels of cytokines such as IL-6, IL-8, and IFNg, [49][50][51][52] our results suggest that inflammatory cytokines released on infection may boost both ILCP development from HSC and its further differentiation into ILC subsets. The long-lasting effect of an early infection on the circulating levels and differentiation capacity of ILCPs may be the result of an ''epigenetic scar'' left by the antimicrobial response.…”

Modulation of B Cells and Homing Marker on NK Cells Through Extracorporeal Photopheresis in Patients With Steroid-Refractory/Resistant Graft-Vs.-Host Disease Without Hampering Anti-viral/Anti-leukemic Effects

“…Therefore, TNF-α inhibitory drugs such as the monoclonal antibodies infliximab and adalimumab are now in use in the clinic for the treatment patients with steroid-refractory GvHD. IL-8 contributes to downstream tissue damage and transplant-related mortality and has been defined as a diagnostic and prognostic biomarker for aGvHD ( 62 , 63 ). In the light of our data, steroids were insufficient to reduce proinflammatory cytokines in all cases since some patients still had high levels of cytokines under the high-dose of immunosuppressive medication.…”