Опубликовать статью

Информационное партнерство

Инфоресурсы

Контакты

«

Vol. 24, Art. 72 (pp. 1060-1069)    |    2023       

»

Intestinal microbiota as a predictor of infection development in hematological cancer patients during hematopoietic stem cell transplantation

Chebotkevich V.N., Kuleshova A.V., Bessmeltsev S.S., Gritsaev S.V., Sidorkevich V.S.

Russian Research Institute of hematology and Transfusiology, Russia

Brief summary

Systemic infections of the bloodstream are formidable, life-threatening complications in immunocompromised oncohematological patients. Their microbiological diagnostics, based on the detection of pathogens in the blood, takes at least 24 hours and allows seeding the pathogen only in 40-60% of cases. It is known that systemic infections of the bloodstream in patients with hemoblastoses during hematopoietic stem cell transplantation (HSCT) are much more often observed with allogeneic than with autologous HSCT. This, as well as the above difficulties in the microbiological diagnosis of bacteremia, significantly complicate the detection of infections in patients with autologous HSCT and dictate the need to develop methods for their prediction. It has been shown that endogenous infection from the intestine plays a leading role in the development of Gram-negative bloodstream infections. Aim. To determine the qualitative and quantitative characteristics of the intestinal microbiome that contribute to the development of infections in patients with multiple myeloma during high-dose chemotherapy and autologous hematopoietic stem cell transplantation. Materials and methods. The study included 30 patients with multiple myeloma aged 48-67 years (median 60 years), from 2020 to 2022, who underwent an autologous HSCT procedure. The study protocol included the collection and low-temperature freezing of stool samples obtained from patients before autologous HSCT and at different times from 7 to 35 days after it. A total of 98 biomaterial samples were obtained. In each of the biological samples, PCR amplification of the V5 region of the 16S rRNA gene was performed using modified universal bacterial primers. Along with sequencing, real-time PCR was performed at the same time, which allows to detect DNA of obligate representatives of the colon microflora (Вifidobacteria, Lactobacilli, Escherichia coli), as well as opportunistic and pathogenic microorganisms, including Clostridium difficile, Enterobacter spp., Salmonella spp, etc. Results. Our studies have shown that a significant (p=0.0215) decrease in the diversity index is also observed in autologous HSCT. The dominance of the Proteobacteria type in the spectrum of the intestinal microbiome is an independent factor in the development of Gram-negative bloodstream infections. Of the patients we observed, the frequency of the type of Proteobacteria averaged from 1 to 6%, only in one case, the detection of the type of Proteobacteria was 40%. Conclusion. The composition of the gut microbiome significantly affects the incidence of infections in patients with multiple myeloma after autologous HSCT. When monitoring microbiome composition, samples should be assessed both before and after HSCT.


Key words

gut microbiota, predictors of infection, multiple myeloma, autologous hematopoietic stem cell transplantation

Reference list

1. Bessmelcev S. S. Mnojestvennaya mieloma / S. S. Bessmelcev, K. M. Abdylkadirov. - M., MK, 2016. - 504 s.


2. Averbuch D., Tridello G., Hoek J. et al. Antimicrobial Resistance in Gram-Negative Rods Causing Bacteremia in Hematopoietic Stem Cell Transplant Recipients: Intercontinental Prospective Study of the Infectious Diseases Working Party of the European Bone Marrow Transplantation Group // Clinical Infectious Diseases. - 2017. - V. 65. - 11. - P. 1819-1828.


3. Stoma I., Littmann E.R., Peled J.U. et al. Compositional Flux Within the Intestinal Microbiota and Risk for Bloodstream // Clinical Infectious Diseases. -2021.- Vol.73. - P. 4627-4635.


4. Rajkumar S.V., Dimopoulos M.A., Palumbo A. et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma // Lancet Oncol. - 2014; -Vol.15, - 12. -P. 538-548.


5. Durie B.G., Salmon S.E. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment and survival // Cancer. - 1975. - Vol. 36. 3.- P. 842-854.


6. Taur Y., Xavier J.B., Pamer E.G. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation // Clinical Infectious Diseases . - 2012. - Vol. 55, No 7. - P. 905-914.


7. Ayres J.S., Trinidad N.J., Vance R.E. Lethal inflammasome activation by a multidrug-resistant pathobiont upon antibiotic disruption of the microbiota. // Nat Med. - 2012 - Vol.18 - 5 - 799-806.


8. Stoma I.O. Mikrobiota kishechnika y pacientov s immynosypressiei: pereocenka vzglyadov na patogenez infekcii krovotoka // Klinicheskaya infektologiya i parazitologiya. - 2018. - T 7, 2. - S. 224-233.


9. Stoma I, Littmann E.R., Pamer E.G. et al. Compositional flux within the intestinal microbiota and risk for bloodstream infection with gram-negative bacteria // Clinical Infectious Diseases.-Vol. 73.- 11.- P. e4627-e4635.