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Patterns of salivary microbiota injury and oral mucositis in recipients of allogeneic hematopoietic stem cell transplantation
Shouval, R., Eshel, A., Dubovski, B., Kuperman, A. A., Danylesko, I., Fein, J. A., Fried, S., Geva, M., Kouniavski, E., Neuman, H., et al
Blood advances. 2020;4(13):2912-2917
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Abstract
Oral mucositis (OM) is a common debilitating dose-limiting toxicity of cancer treatment, including hematopoietic stem cell transplantation (HSCT). We hypothesized that the oral microbiome is disturbed during allogeneic HSCT, partially accounting for the variability in OM severity. Using 16S ribosomal RNA gene sequence analysis, metabolomic profiling, and computational methods, we characterized the behavior of the salivary microbiome and metabolome of 184 patients pre- and post-HSCT. Transplantation was associated with a decrease in oral alpha diversity in all patients. In contrast to the gut microbiome, an association with overall survival was not detected. Among 135 patients given methotrexate for graft-versus-host disease prophylaxis pre-HSCT, Kingella and Atopobium abundance correlated with future development of severe OM. Posttransplant, Methylobacterium species were significantly enriched in patients with severe OM. Moreover, the oral microbiome and metabolome of severe OM patients underwent distinct changes post-HSCT, compared with patients with no or mild OM. Changes in specific metabolites were well explained by microbial composition, and the common metabolic pathway was the polyamines pathway, which is essential for epithelial homeostasis. Together, our findings suggest that salivary microbial composition and metabolites are associated with the development of OM, offering new insights on pathophysiology and potential avenues of intervention.
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Underdiagnosed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) as a major cause of multi-organ failure in acute leukemia transplant patients: an analysis from the EBMT Acute Leukemia Working Party
Bazarbachi, A. H., Al Hamed, R., Labopin, M., Halaburda, K., Labussiere, H., Bernasconi, P., Schroyens, W., Gandemer, V., Schaap, N. P. M., Loschi, M., et al
Bone marrow transplantation. 2020
Abstract
Allogeneic hematopoietic cell transplantation (alloHCT) is a complex, potentially fatal therapy featuring a myriad of complications. Triggering event(s) of such complications vary significantly, but often a so-called "multi-organ failure" (MOF) is reported as the leading cause of death. The identification of the exact trigger of MOF is critical towards early and disease-specific intervention to improve outcome. We examined data from 202 alloHCT patients reported to have died of MOF from the EBMT registry aiming to determine their exact cause of death focusing on veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) due to its life-threatening, often difficult to capture yet preventable nature. We identified a total of 70 patients (35%) for whom VOD/SOS could be considered as trigger for MOF and leading cause of death, among which 48 (69%) were previously undiagnosed. Multivariate analysis highlighted history of hepatic comorbidity or gentuzumab use and disease status beyond CR1 as the only significant factors predictive of VOD/SOS incidence (OR?=?6.6; p?=?0.001 and OR?=?3.3; p?=?0.004 respectively). VOD/SOS-related MOF was widely under-reported, accounting for 27% of deaths attributed to MOF of unknown origin without a previous VOD/SOS diagnosis. Our results suggest most missed cases developed late VOD/SOS beyond 21 days post-alloHCT, highlighting the importance of the newly revised EBMT criteria.
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Risk Factors and Implications of Oral Mucositis in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation
Shouval, R., Kouniavski, E., Fein, J., Danylesko, I., Shem-Tov, N., Geva, M., Yerushalmi, R., Shimoni, A., Nagler, A.
European journal of haematology. 2019
Abstract
BACKGROUND Oral mucositis (OM) is a common toxicity of stem cell transplantation (SCT). We sought to evaluate OM burden, risk factors, and implications in a cohort of allogeneic-SCT recipients. METHODS This was a single center study including 115 adult allogeneic-SCT transplanted between 2016 to 2018 for various hematological conditions. Conditioning intensity was categorized as myeloablative (MAC, 39%), reduced intensity (34%), or reduced toxicity (RTC, 27%) in patients conditioned with Fludarabine-Treosulfan. OM was prospectively graded using the Common Terminology Criteria for Adverse Events (v.4.0) system. RESULTS Moderate to severe OM (grade 2-4) was experienced by 60% of patients. In a univariate analysis, younger age (p=0.023), lower body-mass-index (p=0.01), recent smoking (p=0.08), recent antibiotics exposure (p=0.018), MAC (p<0.001), and methotrexate (p=0.009) were associated with moderate to severe OM. In a multivariable logistic regression model, conditioning and graft-versus-host disease prophylaxis remained significant. OM risk was lowest with RTC (RTC vs. MAC: Odd Ratio [OR] 0.05, p<0.001), and recent antibiotic exposure trended towards increased risk (OR 1.88, p=0.168). OM was associated with longer hospitalization, delayed neutrophil engraftment, and gastrointestinal-related infections. CONCLUSION Oral mucositis remains a leading SCT complication. Treosulfan-based conditioning has low mucosal toxicity and is appealing given previous reports on its high efficacy. This article is protected by copyright. All rights reserved.
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Risk of sinusoidal obstruction syndrome in allogeneic stem cell transplantation after prior gemtuzumab ozogamicin treatment: a retrospective study from the Acute Leukemia Working Party of the EBMT
Battipaglia, G., Labopin, M., Candoni, A., Fanin, R., El Cheikh, J., Blaise, D., Michallet, M., Ruggeri, A., Contentin, N., Ribera, J. M., et al
Bone Marrow Transplantation. 2017;52(4):592-599
Abstract
Gemtuzumab ozogamicin (GO) may increase the risk of sinusoidal obstruction syndrome (SOS) when used prior to allogeneic stem cell transplantation (HSCT). We assessed SOS incidence and outcomes after HSCT of 146 adults, with a median age of 50 years, previously receiving GO. SOS prophylaxis was used in 69 patients (heparin n=57, ursodeoxycholic acid n=8, defibrotide n=4). Cumulative incidence (CI) of SOS was 8% (n=11), with death in 3 patients. Median interval between last GO dose and HSCT was 130 days. Overall survival (OS) and SOS incidence did not differ for patients receiving GO 3.5 months before HSCT and the others. CI of acute and chronic GVHD was 31% and 25%, respectively. Probability of OS and leukemia-free survival (LFS) at 5 years was 40% and 37%, respectively. Relapse incidence and non-relapse mortality were 42% and 21%, respectively. In multivariate analysis, active disease at HSCT was associated with relapse and worse LFS and OS (P<0.03). Liver abnormalities before HSCT correlated with worse OS (P<0.03). Use of low-dose GO prior to HSCT is associated with an acceptable SOS incidence. Prospective studies investigating the role and the utility of SOS prophylaxis are warranted.