Polymorphism of Interleukins and Tumor Necrosis Factor α Genes in Multiple Myeloma Patients with Autologous Hematopoietic Stem Cell Transplantation

AUTOIMMUNE THROMBOCYTOPENIA cytokines, immune response, multiple myeloma

SP Svitina, ZhYu Sidorova, II Kostroma, AA Zhernyakova, AV Chechetkin, ZhV Chubukina, SV Gritsaev, SI Kapustin, SS Bessmeltsev

Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Svetlana Pavlovna Svitina, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; e-mail: shvetikova@gmail.com

For citation: Svitina SP, Sidorova ZhYu, Kostroma II, et al. Polymorphism of Interleukins and Tumor Necrosis Factor α Genes in Multiple Myeloma Patients with Autologous Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2021;14(3):340–6. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-340-346

ABSTRACT

Aim. To assess polymorphism value of interleukins (IL6, IL1B, IL10) and tumor necrosis factor α (TNF) genes in multiple myeloma (MM) patients who received autologous hematopoietic stem cell transplantation (auto-HSCT).

Materials & Methods. The study enrolled 37 MM patients (15 men and 22 women) aged 38–66 years (mean age 54.5 ± 6.4 years), who received auto-HSCT. After transplantation, partial (PR), very good partial (VGPR), and complete (CR) responses were reported in 11, 7, and 19 patients, respectively. In 23 (62.2 %) patients CD34+ cell collection on the day of the first leukocytapheresis session exceeded the suboptimal level of 2.5 × 10⁶/kg. The control group included 236 healthy subjects. Genotyping by PCR with subsequent analysis of restriction fragment length polymorphism of amplified products was performed. To identify between-group differences in genotype distribution, Fisher’s exact test with measurements of odds ratio (OR) and р–value was used.

Results. The study group of patients was distinguished from the control group by more than twofold increased proportion of homozygous IL1B –31C (OR 2.7; p = 0.029). The proportion of heterozygous –174G/C allelic variant of IL6 gene in the subgroup of patients with CR after auto-HSCT was considerably higher than in patients with VGPR and PR (OR 5.6; p = 0.022). In the subgroup of patients with CD34+ cell collection > 2.5 × 10⁶/kg the proportion of those with IL10 –592C/C genotype was twice as high as in patients with lower CD34+ cell collection (OR 3.9; p = 0.091).

Conclusion. The present study confirms the relationship of –31C/Т polymorphism in IL1B gene in homozygous state with higher MM risk. It proved the association of –174G/C polymorphism in IL6 gene and –592C/A polymorphism in IL10 gene with the chosen criteria for auto-HSCT efficacy. To precisely clarify the value of variants in the above genes for predicting chemotherapy effect in MM, further studies involving more patients are required.

Keywords: multiple myeloma, genes polymorphism, immune response, cytokines, autologous hematopoietic stem cell transplantation.

Received: March 4, 2021

Accepted: June 10, 2021

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Prognostic Value of Genetic Markers for Efficacy Estimation of Induction Treatment Including Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients

LYMPHOID TUMORS autologous hematopoietic stem cell transplantation, cytokine, gene polymorphisms, high-dose chemotherapy, immune response, multiple myeloma, Toll-like receptor

EL Nazarova, NV Minaeva, MN Khorobrykh, EE Sukhorukova, VI Shardakov, IV Paramonov, NA Zorina

Kirov Research Institute of Hematology and Blood Transfusion, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027

For correspondence: Elena L’vovna Nazarova, PhD, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; e-mail: nazarova@niigpk.ru

For citation: Nazarova EL, Minaeva NV, Khorobrykh MN, et al. Prognostic Value of Genetic Markers for Efficacy Estimation of Induction Treatment Including Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients. Clinical oncohematology. 2018;11(1):54-69.

DOI: 10.21320/2500-2139-2018-11-1-54-69

ABSTRACT

Aim. To determine the value of polymorphisms of the immune response genes for the treatment efficacy in MM patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (autoHSCT).

Methods. The overall of 20 ММ patients (8 men and 12 women) were included in the study. The median age was 51.5 years (range 32–67). Clinical laboratory tests had been performed before melphalan high-dose (200 mg/m²) conditioning therapy. In accordance with the achieved anticancer response to induction treatment the patients were divided into 3 groups: patients with partial remission (group 1; n = 7); patients with very good partial remission (group 2; n = 9); patients with complete remission (group 3; n = 4). Genotyping of 20 polymorphic loci of 14 immune response genes was performed using PCR.

Results. The study showed that group 2 had no AA mutant homozygotes of IL10 in the G-1082A polymorphic locus compared to group 3 and no TT mutant homozygotes of TLR6 (Ser249Pro) compared to group 1. The patients with more pronounced mucositis (grade 2/3) compared to patients with minor mucositis (grade 0/1) had no CC mutant homozygotes of IL1β in the G-1473C position and a smaller number of (CT+TT) heterozygous and homozygous haplotype carriers of IL10 with the T mutant allele in the C-819T mutation point. The multivariate analysis showed that the genetic marker statistically effecting the progression-free survival rates in MM patients after high-dose chemotherapy and autoHSCT was the polymorphous status of the IL10 (G-1082A), TNF (G-308A), TLR4 (Thr399Ile), and TLR9 in the T-1237C and A2848 polymorphic loci. Progression-free survival rates correlated with the mutation status of IL1β (T-511C), IL2 (T-330G), IL6 (C-174G), CD14 (C-159T), TLR3 (Phe421Leu), and TLR4 (Asp299Gly).

Conclusion. The obtained data show the correlation of 14 polymorphisms of 10 immune response genes with the immediate results of the induction treatment, and also with the severity of mucositis during the early post-transplant period, as well as overall and progression-free survival rates in MM patients. Due to a small sample volume further studies will be planned with the aim to verify the identified trends. The suggested hypothesis for immune response gene polymorphism effecting a disease prognosis can substantially contribute to developing of individualized approach to MM treatment.

Keywords: multiple myeloma, gene polymorphisms, immune response, cytokine, Toll-like receptor, high-dose chemotherapy, autologous hematopoietic stem cell transplantation.

Received: August 18, 2017

Accepted: November 7, 2017

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Clinico-immunological features of invasive aspergillosis in patients with Hodgkin’s disease

INFECTIONS IN ONCOHEMATOLOGY Hodgkin’s lymphoma, immune response, invasive aspergillosis

O.V. Shadrivova¹, Ye.V. Frolova¹, L.V. Filippova¹, A.Ye. Uchevatkina¹, S.N. Khostelidi¹, R.M. Chernopyatova¹, Ye.A. Desyatik¹, A.G. Volkova², Ye.V. Shagdileyeva¹, L.S. Zubarovskaya², A.V.Rysev¹, S.M. Ignatyeva¹, T.S. Bogomolova¹, Yu.N. Vinogradova³, N.V. Vasilyeva¹, and N.N. Klimko¹

¹I.I. Metchnikov Northwest State Medical University, Saint Petersburg, Russian Federation

²R.M. Gorbacheva Institute of Pediatric Oncology, Hematology and Transplantology, I.P. Pavlov Saint Petersburg State Medical University, Saint Petersburg, Russian Federation

³Russian Research Centre for Radiology and Surgical Technologies, RF Ministry of Health, Saint Petersburg, Russian Federation

ABSTRACT

Invasive aspergillosis is a serious mycotic infection with high mortality that mostly occurs in patients with hematological malignancies and severe immunodeficiency. Immunological defects in the various groups of hematological patients with invasive aspergillosis are not well understood. We are the first to present the results of studying clinico-immunological features of invasive aspergillosis in the patients with Hodgkin’s lymphoma.

Keywords: invasive aspergillosis, Hodgkin’s lymphoma, immune response.

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