Alteration of Gut Microbiota Composition and Diversity in Acute and/or Chronic Graft-versus-Host Disease Following Hematopoietic Stem Cell Transplantation: A Prospective Cohort Study.

Changes in gut microbiome composition have been implicated in the pathogenesis of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our objective was to explore the microbial abundance in patients with GvHD after allo-HSCT. We conducted a single-center, prospective study in patients who underwent allo-HSCT and developed grade II or higher acute GvHD and/or moderate or severe chronic GvHD, to explore the microbial abundance of taxa at the phylum, family, genus, and species level, and we utilized alpha and beta diversity indices to further describe our findings. We collected fecal specimens at -2 to +2 (T1), +11 to +17 (T2), +25 to +30 (T3), +90 (T4), and +180 (T5) days to assess changes in gut microbiota, with day 0 being the day of allo-HSCT. We included 20 allo-HSCT recipients in the study. Compared with timepoint T1, at timepoint T4 we found a significant decrease in the abundance of Proteobacteria phylum (14.22% at T1 vs. 4.07% at T4, p = 0.01) and Enterobacteriaceae family (13.3% at T1 vs. <0.05% at T4, p < 0.05), as well as a significant increase in Enterococcus species (0.1% at T1 vs. 12.8% at T4, p < 0.05) in patients who developed acute GvHD. Regarding patients who developed chronic GvHD after allo-HSCT, there was a significant reduction in the abundance of Eurobactereaceae family (1.32% at T1 vs. 0.53% at T4, p < 0.05) and Roseruria genus (3.97% at T1 vs. 0.09% at T4, p < 0.05) at T4 compared with T1. Alpha and beta diversity analyses did not reveal a difference in the abundance of bacteria at the genus level in GvHD patients at T4 compared with T1. Our study reinforces results from previous studies regarding changes in gut microbiota in patients with acute GvHD and provides new data regarding the gut microbiome changes in chronic GvHD. Future studies will need to incorporate clinical parameters in their analyses to establish their association with specific changes in gut microbiota in patients with GvHD after allo-HSCT.

Open-Label Randomized Controlled Study of Ciprofloxacin vs Rifaximin as Neutropenia Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation.

Loss of microbiota diversity has been clearly associated with poor outcomes in the allogeneic hematopoietic stem cell transplantation setting. However, the choice of the optimal antibiotic prophylaxis during the pre-engraftment phase remains unclear. We designed a prospective randomized study to compare our standard-of-care neutropenia prophylaxis (ciprofloxacin) with rifaximin. We enrolled 38 consecutive adult patients who underwent allogeneic hematopoietic stem cell transplantation setting and were randomly assigned to receive ciprofloxacin (20 patients) or rifaximin (18 patients) at day -1. Pretransplant and transplant characteristics did not differ between groups. Cumulative incidence (CI) of acute graft-vs-host disease grade II to IV and moderate/severe chronic graft-vs-host disease was similar in both groups. With a median follow-up of 13.2 months (range, 6.8-30.2) in surviving patients, the 1-year CI of relapse was 20.8% in ciprofloxacin vs 17.8% in rifaximin (P = .616). Importantly, the 1-year CI of treatment-related mortality was significantly reduced in the ciprofloxacin group (10.2% vs 27.8%, P = .032), leading to higher 1-year overall survival (88.9% vs 74.6%, P = .038). In Cox-regression multivariate analysis, antibiotic prophylaxis remained the only predictor of overall survival, independently of donor type, disease risk index, and moderate/severe chronic graft-vs-host disease. Further studies are needed to assess the effects on microbiota diversity and confirm these outcomes.

Risk Factors and Outcomes of Klebsiella pneumoniae Infection Before and After Allogeneic Hematopoietic Cell Transplantation.

Objectives: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) emerge as a major healthcare concern worldwide. Despite the significance of infections before and after allogeneic hematopoietic cell transplantation (alloHCT), the burden of KP infections has not been extensively evaluated. Methods: We studied the incidence, risk factors, and outcomes of consecutive alloHCT recipients with Kp isolates before and after alloHCT. Results: Among 424 patients who underwent alloHCT in 2008-2018, we studied two groups: those with Kp isolates before (group 1, 52 patients) and those with Kp isolates after alloHCT (group 2, 66 patients). prE-transplant infections were associated with post-transplant infections (p = 0.010), despite secondary prophylaxis. KPC-Kp was isolated in 29% of group 1, and 80% of group 2. Both groups were characterized by a significant burden of moderate-severe acute graft- vs.-host disease (GVHD) [cumulative incidence (CI) of 44.5 and 61.9%, respectively] and severe chronic (CI of 56.7 and 61.9%). Kp infections and GVHD were independent predictive factors of treatment-related mortality (TRM) in both groups. Conclusions: Our study highlights the significant impact of Kp infections on TRM, with GVHD consisting an important underlying factor. As prophylactic measures did not improve rates of post-transplant infections, innovative interventions need to be further investigated to address this major healthcare concern.

Nelarabine-associated reversible Guillain-Barré-like syndrome or myelopathy in an adult patient with primary refractory T-lymphoblastic lymphoma.

Nelarabine is a purine analogue used for the treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma mainly as a bridge to stem cell transplantation. The water-soluble prodrug of 9-beta-D-arabinofuranosyl guanine (Ara-G) is phosphorylated within leukemic cells to form ara-G triphosphate (ara-GTP), which terminates DNA chain elongation, resulting in cell death. The drug received accelerated approval by the US Food and Drug Administration (FDA) on October 2005 based on the induction of complete remissions in 2 phase II trials. In these trials, neurologic toxicity was mainly presented as peripheral neuropathy and, since, is a commonly reported side effect of the drug. However, cases of severe grade III, IV, or even fatal neurotoxicity as well as cases of ascending myelopathy have also been reported with most of these cases being irreversible. In this article, we report a reversible grade IV Guillain-Barré-like case of a patient with primary refractory T-cell lymphoblastic lymphoma treated with nelarabine. Guillain-Barré-like syndrome in this patient coexisted with toxic myelopathy which affected the whole spine. The pathogenetic mechanisms and genetic predisposition for nelarabine-associated neurotoxicity is still unknown. The role of the immune system and the patient's genetic background are under investigation along with considerations on the right treatment of the syndrome. Gaining a better understanding in the contributing mechanisms will help us to recognize individuals in danger for neurotoxicity and will lead to the prompt treatment of this complication. Yet, it can be concluded from the present case and literature review that high-dose cytarabine regimens and intrathecal installations should be avoided in close time proximity with nelarabine treatment, as they could enhance neurotoxicity.