Clinical and Genetic Aspects of the Refractory Forms of Multiple Myeloma

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Н. І. Костюкова
З. І. Россоха
Н. Г. Горовенко
С. В. Видиборець

Abstract

Treatment of multiple myeloma has progressed significantly over the past years after the introduction of immunomodulation drugs and proteasome inhibitors, which lead to the overall survival improvement, but still disease has exacerbations (relapses) and remissions. All patients with multiple myeloma have relapses within different interval of time. The duration of achieved remission in patients with a relapse of multiple myeloma becomes shorter with each subsequent case. The choice of regimen for relapse of multiple myeloma is very difficult. It depends on a number of factors, including the previous induction regimen, the number of lines of the previous therapy, and the degree of aggression of relapse. The article is dedicated to the peculiarities of drug resistance development to the first line therapy in patients with multiple myeloma by assessing of genetic markers (deletion variants of GSTT1, GSTM1 genes, GSTP1 (А313G), MDR1 (C3435T)) and clinical-hematological, laboratory characteristics.

The objective: to develop the predictive algorithm for the effectiveness of treatment in patients multiple myeloma by assessing of clinical genetic and laboratory parameters.

Materials and methods. 68 clinical and laboratory indexes and genetic markers (deletion polymorphism of genes GSTT1, GSTM1, polymorphism А313G, C3435T genes GSTP1, MDR1) was studied in 130 patients with multiple myeloma.

Results. It was determined that important predictors of development of refractory forms of multiple myeloma is allelic polymorphism of gene GSTM1, higher level α2-globulin and calcium in blood serum at the disease beginning.

Conclusions. Implementation of predicative algorithm based on assessment of GSTM1-polymorphism, level of α2-globulin and calcium in blood serum before the beginning of treatment raises efficacy of evaluation of individual prognosis for response on treatment.

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How to Cite
Костюкова, Н. І., Россоха, З. І., Горовенко, Н. Г., & Видиборець, С. В. (2019). Clinical and Genetic Aspects of the Refractory Forms of Multiple Myeloma. Family Medicine, (1), 41–45. https://doi.org/10.30841/2307-5112.1.2019.172145
Section
For Practising Physicians
Author Biographies

Н. І. Костюкова, Kyiv Centre of Bone Marrow Transplantology

Nina I. Kostyukova,

Head of Hematology–oncology Department of Preparing for Bone Marrow Transplantation

З. І. Россоха, State Institution «Reference-center for molecular diagnostic of Ministry of Health of Ukraine»

Zoia I. Rossokha,

Director

Н. Г. Горовенко, P.L. Shupyk National Medical Academy of Postgraduate Education

Nataliia G. Gorovenko,

Head of Department of Medical and Laboratory Genetics

С. В. Видиборець, P.L. Shupyk National Medical Academy of Postgraduate Education

Stanislav V. Vydyborets,

Head of Department of Haematology and Transfusiology

References

Gorovenko N., Kostyukova N., Vydyborets S., Kyryachenko S., Gorenko L., Mazurik M., Popova O., Rossokha Z. The association of MDR1 gene C3435T polymorphism with CMV reactivation in patients with multiple myeloma. 27th International Congress of Chemotherapy (ESMID): Milan, Italy, 2011, abstract, p. 1908. https://doi.org/10.1111/j.1469-0691.2011.03558.x

Iskrov I., Lendina I., Suvorov D., Gerasimovich O. Terapija rezidivov i resistentnych form mnozhestvennoj mielomy: klinicheskij opyt [Treatment of relapses and resistant forms of multiple myeloma: case report]. Hematology. Transfusiology. Eastern Europe, 2018, vol.4, no.3, pp. 411–418.

Multiple myeloma: ESMO Clinical practice Guidelines for diagnosis, treatment and follow-up. Leukaemia & Myeloma 2018. ESMO Pocket Guidelines. European Society by Medical Oncology, 123 p.

Rossokha Z., Kostyukova N., Kiryachenko S., Vydyborets S., Gorovenko N. The predictive model of chemotherapy response in multiple myeloma patients. Experimental oncology. 2013, vol. 35, no. 2, p. 145.

Andreeva N.E., Iliashenko E.Yu., Saridi E.Yu. Retrospective analysis of cytostatic therapy of patients with multiple myeloma. Problems of hematology and blood transfusion, 2002, vol. 3, pp. 7–11.

Votiakova O.М. Modern therapy of multiple myeloma. Fundamental and applied researches in oncohematology. Bulletin of Siberian medicine. Supplement 3. 2008, pp. 33–41. PDF

Kriachok І.А. Clinically-laboratory markers of prognosis of disease progression and response on combined treatment including high-dosage chemotherapy and transplantation of stem cells of patients with multiple myeloma. Ukrainian Medical Journal, 2005, no.4, pp. 132–138.

Кriachok І.А. Modern standards of diagnosis and treatment of patients with multiple myeloma. Ukrainian Medical Journal. 2010, no. 2, pp. 91–97. Full text

Мanziuk L.V. Anti RANKL homogeneous antibody and its usage in oncology. Practical oncology. 2011, vol. 12, no. 3, pp. 132–135.

Novosad О.І., Kriachok І.А., Kadnikova Т.V., Тytorenko І.B., Sychova Т.V, Кostiukova N.І. Experience of implementation of thalidomide in treatment multiple myeloma. Likars’ka sprava, 2010, no. 3-4 (1105), pp. 79–86.

Buda G., Maggini V., Galimberti S. at el. MDR1 polymorphism Influences the outcome of multiple myeloma. B. J. Haematol. 2007, no 2, pp. 454–456. https://doi.org/10.1111/j.1365-2141.2007.06605.x

Dumontet C. Landi S., Reimen T. at el. Genetic polymorphisms associated with outcome in multiple myeloma patients receiving high-dose melphalan. Bone Marrow Transplantation. 2010, vol.45, pp. 1316–1324. https://doi.org/10.1038/bmt.2009.335

Lonial Sagar. Relapsed Multiple Myeloma. American Society of Hematology. 2010, pp. 303–309. https://doi.org/10.1182/asheducation-2010.1.303

Richardson P., Mitsiades C., Schlossman R., Ghobrial I., Hideshima T., Chauhan D., Munshi N., Anderson K. Treatment of Relapsed and Refractory Multiple Myeloma. American Society of Hematology. 2007, pp. 317–323. https://doi.org/10.1182/asheducation-2007.1.317