Preview

Journal of Siberian Medical Sciences

Advanced search

Evaluation of probiotics’ effectiveness for correction of dysbiosis and endogenous intoxication in patients with lymphoproliferative diseases

https://doi.org/10.31549/2542-1174-2024-8-4-33-50

Abstract

Introduction. The development of gastrointestinal complications of chemoradiotherapy in patients with hematologic malignancies is based on dysbiotic processes characterized by suppression of normal intestinal microfl ora, activation of opportunistic microorganisms, high risk of their translocation to non-specifi c biotopes, and endogenous infection. Another etiological factor in the development of intestinal dysbiosis in patients with hematologic malignancies  is the use of antibacterial therapy (ABT) amid febrile neutropenia. Thus, the relevance of searching for therapeutic and preventive measures to reduce the number of gastrointestinal complications that arise in antitumor treatment is beyond doubt. The solution to this problem is rational ABT and maintenance therapy with probiotics.

Aim. To evaluate the eff ectiveness of probiotics in patients with lymphomas at the onset  of the disease in order to correct dysbiosis and endogenous intoxication (EI).

Material and methods. A total of 40 patients with lymphomas were included in a prospective randomized study. The average age of the patients was 45 (34; 54.5) years. The distribution of patients by gender was as follows: 4 men (10%), 36 women (90%). Among the subjects, patients with stages III and IV of the disease predominated (n = 26, 65%). In order to evaluate the effi  cacy of a probiotic, the patients were randomly divided into 2 groups: 20 people who, in addition to polychemotherapy (PCT), received the probiotic orally in combination with a metabiotic, and 20 patients with lymphomas from the control group who received only conventional therapy. A comprehensive assessment of the state of the intestinal microbiome was performed using  real-time polymerase chain reaction. Statistical data processing was performed using IBM SPSS Statistics 26.0 program.

Results.  At the disease onset, a pronounced defi ciency of the total bacterial load was observed in 7 patients (17.5%), a defi ciency of bifi dobacteria – in 29 patients (72.5%), a decrease in the  lactobacilli count – in 34 (85%) patients.  An imbalance in anaerobic fl ora prevailed in patients with aggressive B-cell lymphomas compared to patients with  indolent  tumor (χ2 = 4.1, p = 0.04). The microbiome  with abundance of E. coli was more often diagnosed in patients with  localized tumors compared to those with stages III and IV of the disease (χ2 = 4.6, p = 0.03). Clinical manifestations of intestinal dysbiosis at the onset of the disease were characterized by the following symptoms: abdominal pain (n = 4, 10%), fl atulence (n = 6, 15%), a feeling of incomplete evacuation (n = 2, 5%), diarrhea (n = 8, 20%). In patients receiving probiotics as maintenance therapy, the count of Bifi dobacterium spp. (p = 0.000005), Lactobaccilus spp. (p = 0.00007) and Faecalibacterium prausnitzii (p = 0.003) was signifi cantly higher compared to the results of patients who received only standard courses of polychemotherapy. Comparative assessment of median concentrations of biochemical parameters demonstrated that in patients receiving the probiotic, the concentration of lactate dehydrogenase (p = 0.000001) and C-reactive protein (p = 0.04) was signifi cantly lower compared to the control group who did not receive pro- and metabiotics. More  pronounced leukocytosis (p = 0.0005) and accelerated erythrocyte sedimentation (p = 0.002) were noted in patients from the control group. At the same time, it was found that in the group of patients who received the probiotic before the start of antitumor treatment, nausea (χ2 = 10.9, p = 0.0009), fl atulence (χ2 = 4.3, p = 0.03), and diarrhea (χ2 = 4.2, p = 0.04) associated with chemotherapy were signifi cantly less common.

Conclusion. Intestinal dysbiosis in patients with hematologic malignancies has a multifactorial nature, caused by destructive processes in the body due to growth and spread of tumor, disorder of the functional state of various organs, empiric antibacterial therapy and the administration of high doses of cytostatic drugs. The use of probiotics as part of combined therapy for patients with lymphomas will signifi cantly reduce the severity of intestinal dysbiosis and improve  polychemotherapy results.

About the Authors

M. S. Voitko
Novosibirsk State Medical University
Russian Federation

Maria S. Voitko – Cand. Sci. (Med.), Assistant Professor, Department of Therapy, Hematology and Transfusiology

52, Krasny prosp., Novosibirsk, 630091



O. V. Sorokin
VedaGenetika, LLC
Russian Federation

Oleg V. Sorokin – Cand. Sci. (Med.), Executive Director, National Ayurvedic Medical Association; Director General

Novosibirsk



S N. Zinatulin
VedaGenetika, LLC
Russian Federation

Sergey N. Zinatulin – Medical Adviser

Novosibirsk



N. V. Skvortsova
Novosibirsk State Medical University
Russian Federation

Natalia V. Skvortsova – Dr. Sci. (Med.), Associate Professor, Department of Therapy, Hematology and Transfusiology

Novosibirsk



A. A. Korotchenko
Novosibirsk State Medical University
Russian Federation

Alena A. Korotchenko – 6-year Student

Novosibirsk



A. A. Trubnikova
Novosibirsk State Medical University
Russian Federation

Arina A. Trubnikova – 4-year Student

Novosibirsk



References

1. . Bondarenko S.N., Parovichnikova E.N., Maschan A.A. et al. Blinatumomab in the treatment of acute lymphoblastic leukemia: Russian multicenter clinical trial. Clinical Oncohematology. 2019;12(2):145-153. DOI: 10.21320/2500-2139-2019-12-2-145-153. (In Russ.)

2. Ovechkina V.N., Bondarenko S.N., Morozova E.V. et al. Acute myeloblastic leukemia and myelodysplastic syndrome: azacitidine for prophylactic and preventive purposes after allogeneic hematopoietic stem cell transplantation. Clinical Oncohematology. 2017;10(1):4551. DOI: 10.21320/2500-2139-2017-10-1-45-51. (In Russ.)

3. Schmid C., Labopin M., Nagler A. et al.; Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation. Treatment, risk factors, and outcome of adult with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation. Blood. 2012;119(6):1599-1606. DOI: 10.1182/blood-2011-08-375840.

4. Christopeit M., Kuss O., Finke J. et al. Second allograft for hematologic relapse of acute leukemia after fi rst allogeneic stem-cell transplantation from related and unrelated donors: the role of donor change. J. Clin. Oncol. 2013;31(26):3259-3271. DOI: 10.1200/jco.2012.44.7961.

5. Kröger N., Stübig T., Atanackovic D. Immune-modulating drugs and hypomethylating agents to prevent or treat relapse after allogeneic stem cell transplantation. Biol. Blood Marrow Transplant. 2014;20(2):168-172. DOI: 10.1016/j.bbmt.2013.09.009.

6. Nikitin E.A., Sharkunov N.N., Markaryan V.G. et al. Treatment patterns, outcomes and long-term toxicity among patients with Hodgkin’s lymphoma in real world: results of a hospital based registry. Oncohematology. 2016; 11(3):8-19. DOI: 10.17650/1818-8346-2016-11-3-8-19. (In Russ.)

7. Kaplanov K.D., Volkov N.P., Klitochenko T.Yu. et al. Hodgkin’s lymphoma: analysis results of Volgograd regional registry. Clinical Oncohematology. 2019; 12(4):363-376. DOI: 10.21320/2500-2139-2019-12-4-363-376. (In Russ.)

8. Mochkin N.E., Sarzhevskii V.O., Dubinina Yu.N. et al. Outcome of classical Hodgkin’s lymphoma treatment based on high-dose chemotherapy and autologous hematopoietic stem cell transplantation: the experience in the NI Pirogov Russian National Medical Center of Surgery. Clinical Oncohematology. 2018;11(3):234240. DOI: 10.21320/2500-2139-2018-11-3-234-240. (In Russ.)

9. Von Treskow B., Kreissl S., Goergen H. et al. Intensive treatment strategies in advanced stage Hodgkin’s lymphoma (HD9 and HD12): analysis of long-term survival in two randomised trial. Lancet Haematol. 2018;5(10):e462-e473. DOI: 10.1016/S2352-3026(18)30140-6.

10. Voitko M.S., Pospelova T.I., Nechunaeva I.N., Shebunyaeva Ya.Yu. Long-term results of classical Hodgkin’s lymphoma treatment in real-world clinical practice: experience of Novosibirsk hematological unit. Clinical Oncohematology. 2023;16(2):192-199. DOI: 10.21320/2500-2139-2023-16-2-192-199. (In Russ.)

11. Poddubnaya I.V., Savchenko V.G. (eds.) (2018). Russian Clinical Guidelines for the Diagnosis and Treatment of Lymphoproliferative Diseases; Russian Society of Oncohematologists; Russian Medical Academy of Post-graduate Education of the Ministry of Health of the Russian Federation; National Hematologic Society. Moscow: Buki Vedi. (In Russ.)

12. Pospelova T.I., Soldatova G.S., Purtova L.A. et al. Longterm results of antitumor therapy for hemoblastoses and approaches to patient rehabilitation. Hematology and Transfusiology. 2012;57(S3):73-74. (In Russ.)

13. Danilenko A.A. (2017). Long-term results of radiation and chemoradiotherapy in primary patients with Hodgkin’s lymphoma. Dr. Sci. (Med.) thesis. Obninsk. 52 p. (In Russ.)

14. Lin Z., Mao D., Jin C. et al. The gut microbiota correlate with the disease characteristics and immune status of patients with untreated diff use large B-cell lymphoma // Front. Immunol. 2023;14:1105293. DOI: 10.3389/fimmu.2023.1105293.

15. Lu D., Yan J., Liu F. et al. Probiotics in preventing and treating chemotherapy-induced diarrhea: a metaanalysis // Asia Pac. J. Clin. Nutr. 2019;28(4):701-710. DOI: 10.6133/apjcn.201912_28(4).0005.

16. Liu Y.C., Wu C.R., Huang T.W. Preventive eff ect of probiotics on oral mucositis induced by cancer treatment: a systematic review and meta-analysis // Int. J. Mol. Sci. 2022;23(21):13268. DOI: 10.3390/ijms232113268.

17. Kim Y.J., Yu J., Park S.P. et al. Prevention of radiotherapy induced enteropathy by probiotics (PREP): protocol for a double-blind randomized placebo-controlled trial // BMC Cancer. 2021;21(1):1032. DOI: 10.1186/s12885-021-08757-w.

18. Diefenbach C.S., Peters B.A., Li H. et al. Microbial dysbiosis is associated with aggressive histology and adverse clinical outcome in B-cell non-Hodgkin lymphoma // Blood Adv. 2021;5(5):1194-1198. DOI: 10.1182/bloodadvances.2020003129.


Review

For citations:


Voitko M.S., Sorokin O.V., Zinatulin S.N., Skvortsova N.V., Korotchenko A.A., Trubnikova A.A. Evaluation of probiotics’ effectiveness for correction of dysbiosis and endogenous intoxication in patients with lymphoproliferative diseases. Journal of Siberian Medical Sciences. 2024;8(4):33-50. (In Russ.) https://doi.org/10.31549/2542-1174-2024-8-4-33-50

Views: 143


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2542-1174 (Print)