Preview

Russian Journal of Pediatric Hematology and Oncology

Advanced search

Method for assessing the effect of antitumor treatment using the leukocyte ratio index in pubertal children with Hodgkinʼs lymphoma

https://doi.org/10.21682/2311-1267-2025-12-1-39-47

Abstract

Relevance. Modern advances in risk-adapted chemotherapy allow achieving long-term overall survival in 97.7 % of children with classical Hodgkin lymphoma (cHL), even at widespread stages of the disease. However, relapses and refractory course of cHL are noted in 10 % of cases. In this regard, the search for additional prognostic factors for the course of HL continues.

The aim of the study – to evaluate the significance of using the leukocyte ratio index to assess the effectiveness of antitumor treatment in pubertal children with cHL.

Materials and methods. The study included children of both genders (22 boys and 18 girls) with a morphoimmunohistochemically confirmed diagnosis of cHL. Before treatment and after each course of chemotherapy, the general blood test parameters were determined with subsequent calculation of the leukocyte ratio using the formula: the absolute number of neutrophils was divided by the absolute number of lymphocytes. The results of the study of the leukocyte ratio of 40 conditionally healthy pubertal children in equal sex numbers were used as normal indicators. Statistical processing of the results was performed using the STATISTICA 10.0 program.

Results. In all children with cHL, the leukocyte ratio values exceeded the values of conditionally healthy children from 2.4 to 4.4 times, while there was an increase in the leukocyte ratio by 1.7 times in children with advanced (III, IV) stages of the tumor process compared to stage II. Retrospective analysis of the leukocyte ratio values in children of both genders with HL with remission achieved due to the first line of therapy before treatment demonstrated an increase in the leukocyte ratio by 3.5 times in boys and 4.1 times in girls. At all stages of treatment from the 1st to the 6th course, a statistically significant decrease in the studied indicator was revealed compared to the value of the indicator before treatment in boys by an average of 3.6 times, and in girls by an average of 4.3 times. The indicator was within the reference values of the norm. Retrospective analysis of the leukocyte ratio values in adolescent children with refractory and progressive cHL (4 boys and 3 girls) revealed that before treatment, compared to the norm, the average value was 2.6 times higher in boys and 4.2 times higher in girls. Compared with the initial values of the leukocyte ratio in adolescent children with cHL and remission achieved due to the first line of therapy, the data obtained are statistically insignificant. Having analyzed the leukocyte ratio values after each course of polychemotherapy for each patient in particular, it turned out that the indicator statistically significantly increased after those courses in which refractory course or progression of the disease was detected clinically and diagnostically (ultrasound examination, CT, PET/CT). The leukocyte ratio indicator responded by changing the value depending on the effect of subsequent lines of therapy.

Conclusions. In addition to objective instrumental and laboratory methods for assessing the effectiveness of specialized therapy (PET/CT with 18F-fluorodeoxyglucose, biopsy of the residual neoplasm), as an additional method for assessing the effectiveness of antitumor therapy in pubertal children with cHL, it is also possible to use the leukocyte ratio index based on the results of a complete blood count, which allows indirectly judging the effectiveness of the therapy and timely detection of refractory course or progression of cHL.

About the Authors

E. M. Frantsiyants
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

Dr. of Sci. (Biol.), Professor, Deputy Director General for Science

63 14th line St., Rostov-on-Don, 344037

Web of Science ResearcherID: Y-1491-2018 



V. A. Bandovkina
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

Dr. of Sci. (Biol.), Leading Researcher at the Laboratory for the Study of the Pathogenesis of Malignant Tumors

63 14th line St., Rostov-on-Don, 344037

Web of Science ResearcherID: AAG-8708-2019



D. A. Dzhavadov
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

Postgraduate Student, Pediatric Oncologist Department of Pediatric Oncology No. 1 

63 14th line St., Rostov-on-Don, 344037



Yu. Yu. Kozel
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

Dr. of Sci. (Med.), Professor, Head of the Departments of Pediatric Oncology No. 1 and No. 2

63 14th line St., Rostov-on-Don, 344037



V. V. Dmitrieva
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

Cand. of Sci. (Med.), Pediatric Oncologist Department of Pediatric Oncology No. 1

63 14th line St., Rostov-on-Don, 344037



O. V. Kozyuk
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

Pediatric Oncologist Department of Pediatric Oncology No. 1

63 14th line St., Rostov-on-Don, 344037



D. Yu. Yurchenko
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

Cand. of Sci. (Med.), Pediatric Oncologist Department of Pediatric Oncology No. 2

63 14th line St., Rostov-on-Don, 344037



O. P. Popovyan
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

Cand. of Sci. (Med.), Pediatric Oncologist Department of Pediatric Oncology No. 2

63 14th line St., Rostov-on-Don, 344037



A. V. Snezhko
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

Dr. of Sci. (Med.), Surgeon Department of Abdominal Oncology No. 1

63 14th line St., Rostov-on-Don, 344037



K. S. Aslanyan
Regional Childrenʼs Clinical Hospital
Russian Federation

Cand. of Sci. (Med.), Director of the Center for Childrenʼs Oncology and Hematology 

14 Strelkovoy Divizii St., Rostov-on-Don, 344015



References

1. Belyaeva E.S., Susuleva N.A., Valiev T.T. The importance of intensive chemotherapy for advanced Hodgkin lymphoma in children. Russkiy meditsinskiy zhurnal. Matʼ i ditya = Russian Journal of Woman and Child Health. 2020;3(2):149–53. (In Russ.)].

2. Kulichkina N.S., Belyaeva E.S., Popa A.V., Valiev T.T., Odzharova A.A., Mentkevich G.L. The predictive role of interim pet-ct in the treatment of Hodgkinʼs lymphoma in children. Sovremennaya onkologiya = Journal of Modern Oncology. 2017;19(3):52–6. (In Russ.)].

3. Tsaplina N.S., Kozlov A.V., Valiev T.T., Batmanova N.A., Kazantsev I.V., Kirgizov K.I., Zubarovskaya L.S., Varfolomeeva S.R. Treatment of children with relapsed and refractory classical Hodgkin’s lymphoma: the experience of two centers. Rossiyskiy zhurnal detskoy gematologii i onkologii = Russian Journal of Pediatric Hematology and Oncology. 2024;11(3):22–9. (In Russ.)].

4. Masel R., Roche M.E., Martinez-Outschoorn U. Hodgkin Lymphoma: A disease shaped by the tumor micro- and macroenvironment. Best Pract Res Clin Haematol. 2023;36(4):101514. doi: 10.1016/j.beha.2023.101514.

5. Weniger M.A., Kuppers R. Molecular biology of Hodgkin lymphoma. Leukemia. 2021;35(4):968–81. doi: 10.1038/s41375-021-01204-6.

6. Wang J., Zhang F., Jiang F., Hu L., Chen J., Wang Y. Distribution and reference interval establishment of neutral-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-tolymphocyte ratio (PLR) in Chinese healthy adults. J Clin Lab Anal. 2021;35(9):e23935. doi: 10.1002/jcla.23935.

7. Forget P., Khalifa C., Defour J.P., Latinne D., Van Pel M.C., De Kock M. What is the normal value of the neutrophil-to-lymphocyte ratio? BMC Res Notes. 2017;10(1):12. doi: 10.1186/s13104-016-2335-5.

8. Fest J., Ruiter R., Ikram M.A., Voortman T., van Eijck C.H.J., Stricker B.H. Reference values for white blood-cell-based infl ammatory markers in the Rotterdam Study: a population-based prospective cohort study. Sci Rep. 2018;8(1):10566. doi: 10.1038/s41598-018-28646-w.

9. Zahorec R. Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic infl ammation and stress in critically ill. Bratisl Lek Listy. 2001;102(1):5–14. PMID: 11723675.

10. Bayraktaroglu M., Yildiz B.P. Prognostic signifi cance of neutrophilto-lymphocyte ratio and platelet-to-lymphocyte ratio in non-small cell lung cancer. Medicine (Baltimore). 2023;102(26):e34180. doi: 10.1097/MD.0000000000034180.

11. Naszai M., Kurjan A., Maughan T.S. The prognostic utility of pretreatment neutrophil-to-lymphocyte-ratio (NLR) in colorectal cancer: A systematic review and meta-analysis. Cancer Med. 2021;10(17):5983–97. doi: 10.1002/cam4.4143.

12. Trinh H., Dzul S.P., Hyder J., Jang H., Kim S., Flowers J., Vaishampayan N., Chen J., Winer I., Miller S. Prognostic value of changes in neutrophil-to-lymphocyte ratio (NLR), platelet-tolymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) for patients with cervical cancer undergoing defi nitive chemoradiotherapy (dCRT). Clin Chim Acta. 2020;510:711–6. doi: 10.1016/j.cca.2020.09.008.

13. Marchioni M., Primiceri G., Ingrosso M., Filograna R., Castellan P., De Francesco P., Schips L. The Clinical Use of the Neutrophil to Lymphocyte Ratio (NLR) in Urothelial Cancer: A Systematic Review. Clin Genitourin Cancer. 2016;14(6):473–84. doi: 10.1016/j.clgc.2016.04.008.

14. Frantsiyants E.M., Bandovkina V.A., Kushtova L.B., Nikolaeva N.V., Lysenko I.B., Pushkareva T.F., Kapuza E.A. Possibility of predicting the development of relapse in diff use large B-cell lymphoma using indicators of a general blood test. Sovremennyye problemy nauki i obrazovaniya = Modern Problems of Science and Education. 2021;3. (In Russ.)].

15. Dogan A., Demircioglu S. Assessment of the Neutrophil-Lymphocyte Ratio in Classic Hodgkin Lymphoma Patients. Pak J Med Sci. 2019;35(5):1270–5. doi: 10.12669/pjms.35.5.601.

16. Hajder J., Natasa S., Dragomir M., Olivera M., Radmila Z., Jurisic V. Neutrophil to Lymphocite Ratio Predicts Overall Survival in Newly Diagnosed Hodgkin Lymphoma Patients-Single Centre Experience. Clin Hematol Res. 2021;4. doi: 10.36959/831/384.

17. Mirzayeva G., Kupeli S., Ozkan A., Sezgin G., Bayram I. Associations between neutrophil‐to‐lymphocyte ratio and platelet‐to‐lymphocyte ratio and prognosis in patients with neuroblastoma. Pediatr Blood Cancer. 2023;70(12):e30695. doi: 10.1002/pbc.30695.

18. Xie T., Hou D., Wang J., Zhao S. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as predictive markers in hepatoblastoma. Front Pediatr. 2023;11:904730. doi: 10.3389/fped.2023.904730.

19. Bastard P., Cozic N., Brion R., Gaspar N., Piperno-Neumann S., Cordero C., Leculee-Thebaud E., Gomez-Mascard A., Redini F., Marchais A., Ikonomova R., Cleirec M., Laurence V., Rigaud C., Abbas R., Verrecchia F., Brugières L., Minard-Colin V. Prognostic value of hemogram parameters in osteosarcoma: The French OS2006 experience. Pediatr Blood Cancer. 2024;(7):e31029. doi: 10.1002/pbc.31029.

20. Gulturk E., Kapucu K., Akkaya E., Yılmaz D., Hindilerden F. Systemic Immune-Infl ammation Index and Hodgkin Lymphoma: an Underexplored Relationship. Acta Haematol Oncol Turc. 2023;56(3):259–71. doi: 10.5505/aot.2023.62582.

21. Jan S., Mustafa O., Elgaml A., Ahmad N., Abbas A., Althubaiti S. Neutrophil-to-Lymphocyte Ratio and Ferritin as Measurable Tools for Disease Burden and B Symptoms in Pediatric Patients With Hodgkin Lymphoma. J Pediatr Hematol Oncol. 2022;44(2):e567–71. doi: 10.1097/MPH.0000000000002346.

22. Tezol O., Bozlu G., Sagcan F., Tuncel Daloglu F., Citak C. Value of neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio and red blood cell distribution width in distinguishing between reactive lymphadenopathy and lymphoma in children. Bratisl Lek Listy. 2020;121(4):287–92. doi: 10.4149/BLL_2020_045.

23. Paderina A.S., Valiev T.T. The administration of PD-1 and PD-L1 inhibitors in pediatric hematology: a literature review. Pediatricheskaya farmakologiya = Pediatric Pharmacology. 2024;21(3):240–8. (In Russ.)].

24. Valiev T.T., Morozova O.V., Kovrigina A.M., Makhonova L.A., Sholokhova E.N., Serebryakova I.N., Popa A.V., Tupitsyn N.N., Mentkevich G.L. Diagnosis and treatment of anaplastic large-cell lymphomas in children. Gematologiya i transfuziologiya = Hematology and Transfusiology. 2012;57(1):3–9. (In Russ.)].

25. Nagpal P., Descalzi-Montoya D.B., Lodhi N. The circuitry of the tumor microenvironment in adult and pediatric Hodgkin lymphoma: cellular composition, cytokine profi le, EBV, and exosomes. Cancer Rep (Hoboken). 2021;4(2):e1311. doi: 10.1002/cnr2.1311.

26. Menendez V., Solorzano J.L., Fernandez S., Montalban C., Garcia J.F. The Hodgkin Lymphoma Immune Microenvironment: Turning Bad News into Good. Cancers. 2022;14:1360. doi: 10.3390/cancers14051360.

27. Gusak A., Fedorova L., Lepik K., Volkov N., Popova M., Moiseev I., Mikhailova N., Baykov V., Kulagin A. Immunosuppressive Microenvironment and Effi cacy of PD-1 Inhibitors in Relapsed/ Refractory Classic Hodgkin Lymphoma: Checkpoint Molecules Landscape and Macrophage Populations. Cancers. 2021;13:5676. doi: 10.3390/cancers13225676.

28. Cellini A., Scarmozzino F., Angotzi F., Ruggeri E., Dei Tos A.P., Trentin L., Pizzi M., Visentin A. Tackling the Dysregulated Immune- Checkpoints in Classical Hodgkin Lymphoma: Bidirectional Regulations Between the Microenvironment and Hodgkin/ReedSternberg Cells. Front Oncol. 2023;13:1203470. doi: 10.3389/fonc.2023.1203470.

29. Veldman J., Visser L., Berg A.V.D., Diepstra A. Primary and Acquired Resistance Mechanisms to Immune Checkpoint Inhibition in Hodgkin Lymphoma. Cancer Treat Rev. 2020;82:101931. doi: 10.1016/j.ctrv.2019.101931.

30. Kit O.I., Frantsiyants E.M., Shikhlyarova A.I., Neskubina I.V. Mitochondrial transplantation: new challenges for cancer. Yuzhno-Rossiyskiy onkologicheskiy zhurnal = South Russian Journal of Cancer. 2024;5(1):60–70. (In Russ.)].

31. Ribatti D., Tamma R., Annese T., Ingravallo G., Specchia G. Infl ammatory microenvironment in classical Hodgkin’s lymphoma with special stress on mast cells. Front Oncol. 2022;12:964573. doi: 10.3389/fonc.2022.964573.

32. Zerangian N., Erabi G., Poudineh M., Monajjem K., Diyanati M., Khanlari M., Khalaji A., Allafi D., Faridzadeh A., Amali A. Venous Thromboembolism in Viral Diseases: A Comprehensive Literature Review. Health Sci Rep. 2023;6:e1085. doi: 10.1002/hsr2.1085.


Review

For citations:


Frantsiyants E.M., Bandovkina V.A., Dzhavadov D.A., Kozel Yu.Yu., Dmitrieva V.V., Kozyuk O.V., Yurchenko D.Yu., Popovyan O.P., Snezhko A.V., Aslanyan K.S. Method for assessing the effect of antitumor treatment using the leukocyte ratio index in pubertal children with Hodgkinʼs lymphoma. Russian Journal of Pediatric Hematology and Oncology. 2025;12(1):39-47. (In Russ.) https://doi.org/10.21682/2311-1267-2025-12-1-39-47

Views: 105


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


ISSN 2311-1267 (Print)
ISSN 2413-5496 (Online)
X