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Abrosimov A.B., Blinov D.S., Blinova E.V., Maschan M.A.
Results of a Comparative Phrmacoeconomics Analysis of Strategies for the Prevention of Graft-Versus-Host Disease in Children With Hematological Malignances: a Single Center Experience
Keywords: Pharmacoeconomic analysis, Markov model, clinical and economic efficiency, cost estimation, GVHD, HSCT, cyclophosphamide, TCRa/b/CD19 depletion, hematological malignancies, children
The discussion around the cost of allogeneic hematopoietic stem cell transplantation and follow-up of patients, methods of calculation and cost structure, despite the breadth of application of hematopoietic stem cell transplantation in oncohematological practice, remains an unresolved problem. The discussion is complicated using various modifications of therapeutic options regarding the preparation of the patient for surgery and the prevention of complications. The purpose of this article is a comparative assessment of the clinical and economic efficiency of the two most used technological platforms – TCRαβ/CD19 depletion and ‘’in vivo’’ depletion with high doses of cyclophosphamide, having studied the features of each of these methods in the real practice of one center. Materials and Methods. For evaluation, two “match paired” groups of children were selected, who underwent transplantation according to one of the methods for hemoblastosis in the period from May 2013 to January 2021 at the National Medical Research Center for Pediatric Hematology, oncology and immunology named after Dmitry Rogachev" of the Ministry of Health of Russia. Based on the obtained indicators of clinical effectiveness (significance of differences was made using the nonparametric Mann-Whitney test), pharmacoeconomic modeling was carried out on the basis of the Markov model, the cost structure was determined and the pharmacoeconomic analysis "cost-effectiveness" was performed, incremental analysis "cost-effectiveness" ”, as well as the calculation of indicators of the cost of the operation after 5 years, taking into account discounting. The results of overall and event-free survival, as well as survival without the development of graft-versus-host disease and relapse were used as endpoints. The costs are divided into 2 time periods: stage 1 – up to 30 days after HSCT and stage 2 – from 31 days after HSCT and up to 1 year. Costs are divided into direct and indirect. For indirect costs, the average figures of the available socio-economic data are taken. Results of the study: The total costs for the two stages were comparable for both platforms: TCRa/b/CD19 deletions – 6702.094 thousand rubles; PtCy – 7325.661 thousand rubles. The costs are unevenly distributed over the stages: the 1st stage is more expensive for the TCR platform, the second for PtCy. In cost-effectiveness analysis, each unit of efficiency (1% survival per 1 year of curation will cost more for the PtCy platform. Given the WHO recommended discount factor of 3% per year, over 5 years, the annual cost for the TCR method should decrease to 5933.316 thousand rubles, and for the PtСy platform up to 6,485.355 thousand rubles without considering macroeconomic indicators. Each additional unit of efficiency (1% survival rate) of TCR will cost: survival rate of 207 855.67 rubles, for survival without GVHD and recurrence of 51 963.92 rubles. Conclusions. Pharmacoeconomically less costly for a period of 1 year of curation is the preventive TCR platform compared to the depletion platform ''in vivo'' using high doses of cyclophosphamide, despite the higher cost of its use at the 1st stage of curation.
References
- Musina N.Z., Omel’yanovskii V.V., Gostishchev R.V. et al. Kontseptsiya tsennostnoorientirovannogo zdravookhraneniya [Concept of value-based healthcare]. Sovremennaya farmakoekonomika i farmakoepidemiologiya, 2020, vol. 13(4), pp. 438–451. DOI: https://doi.org/10.17749/2070-4909/farmakoekonomika.2020.042.
- Onkogematologicheskaya pomoshch’ vzroslomu naseleniyu v Rossii: sotsial’no-ekonomicheskoe issledovanie [Oncohematological care for the adult population in Russia: socio-economic research]. Available at: https://tinkovfund.org/research.
- Yagudina R.I., A.Y. Kulikov, Serpik V.G. Farmakoekonomika [Pharmacoeconomics]. Rostov on the Don, Feniks Publ., 2018, 237 p.
- Broder M.S., Quock T.P., Chang E. et al. The Cost of Hematopoietic Stem-Cell Transplantation in the United States. Am Health Drug Benefits, 2017, vol. 10(7), pp. 366–374.
- Ciurea S., Zhang M-J., Bacigalupo A., Bashey A. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood., 2015, vol. 126, pp. 1033–1040. DOI: 10.1182/blood-2015-04-639831.
- Kleinschmidt K., Lv M., Yanir A., Palma J. et al. T-Cell-Replete Versus ex vivo T-Cell-Depleted Haploidentical Haematopoietic Stem Cell Transplantation in Children With Acute Lymphoblastic Leukaemia and Other Haematological Malignancies. Front Pediatr., 2021, vol. 9, 794541. DOI: 10.3389/fped.2021.794541.
- Majhail N.S., Mau L.W., Denzen E.M., Arneson T.J. Costs of autologous and allogeneic hematopoietic cell transplantation in the United States: a study using a large national private claims database. Bone Marrow Transplant., 2013, vol. 48(2), pp. 294–300. DOI: 10.1038/bmt.2012.133.
- Maschan M., Shelikhova L., Ilushina M. et al. Outcome of αβ T cell-depleted transplantation in children with high-risk acute myeloid leukemia, grafted in remission. Bone Marrow Transplant., 2020, vol. 55(1), pp. 256–259. DOI: 10.1038/s41409-019-0531-3.
- Mayerhoff L., Lehne M., Hickstein L. et al. Cost associated with hematopoietic stem cell transplantation: a retrospective claims data analysis in Germany. J Comp Eff Res., 2019, vol. 8(2), pp. 121–131. DOI: 10.2217/cer-2018-0100.
- Pérez-Martínez A., Ferreras C., Pascual A. et al. Haploidentical transplantation in high-risk pediatric leukemia: A retrospective comparative analysis on behalf of the Spanish working Group for bone marrow transplantation in children (GETMON) and the Spanish Grupo for hematopoietic transplantation (GETH). Am J Hematol., 2020, vol. 95(1), pp. 28– DOI: 10.1002/ajh.25661.
- Ricci A., Jin Z., Broglie L. et al. Healthcare utilization and financial impact of acute-graft-versus host disease among children undergoing allogeneic hematopoietic cell transplantation. Bone Marrow Transplant., 2020, vol. 55(2), pp. 384–392. DOI: 10.1038/s41409-019-0688-9.
- Shelikhova L., Glushkova S., Nikolaev R. et al. Serotherapy-Free Regimen Improves Non-Relapse Mortality and Immune Recovery Among the Recipients of αβTCell-Depleted Haploidentical Grafts: Retrospective Study in Childhood Leukemia. Transplant Cell Ther., 2021, vol. 27(4), pp. 330.e1-330.e9. DOI: 10.1016/j.jtct.2021.01.010.
- Symons H.J., Zahurak M., Cao Y. et al. Myeloablative haploidentical BMT with posttransplant cyclophosphamide for hematologic malignancies in children and adults. Blood Adv., 2020, vol. 4(16), pp. 3913–3925. DOI: 10.1182/bloodadvances.2020001648.
About authors
- Abrosimov Andrei B.
- Researcher, Department of Scientific Design and Controlled Clinical Trials, Dmitry Rogachev National Research Medical Center of Pediatric Hematology, Oncology and Immunology, Russia, Moscow (a.b.abrosimov@ya.ru; ORCID: https://orcid.org/0000-0002-0676-6694)
- Blinov Dmitry S.
- Doctor of Medical Sciences, Associate Professor, Head of Molecular and Clinical Pharmacology Department, Dmitry Rogachev National Research Medical Center of Pediatric Hematology, Oncology and Immunology, Russia, Moscow (blinov-pharm@yandex.ru; ORCID: https://orcid.org/0000-0002-8385-4356)
- Blinova Ekaterina V.
- Doctor of Medical Sciences, Professor, Department of Operative Surgery and Topographic Anatomy, I.M. Sechenov First Moscow State Medical University (Sechenovskiy University), Russia, Moscow (bev-sechenov@mail.ru; ORCID: https://orcid.org/0000-0003-0050-0251)
- Maschan Mikhail A.
- Doctor of Medical Sciences, Professor, Deputy General Director – Director of the Institute of Molecular and Experimental Medicine, Dmitry Rogachev National Research Medical Center of Pediatric Hematology, Oncology and Immunology, Russia, Moscow (mmaschan@yandex.ru; ORCID: https://orcid.org/0000-0003-1735-0093)
Article link
Abrosimov A.B., Blinov D.S., Blinova E.V., Maschan M.A. Results of a Comparative Phrmacoeconomics Analysis of Strategies for the Prevention of Graft-Versus-Host Disease in Children With Hematological Malignances: a Single Center Experience [Electronic resource] // Acta medica Eurasica. – 2023. – №1. P. 1-10. – URL: https://acta-medica-eurasica.ru/en/single/2023/1/1/. DOI: 10.47026/2413-4864-2023-1-1-10.