Aim. To conduct an interim outcome analysis of conditioning regimens with carfilzomib or thiotepa compared to standard melphalan 200 mg/m2 regimen in multiple myeloma (MM) patients with single autologous hematopoietic stem cell transplantation (auto-HSCT). Materials & Methods. The retrospective analysis focused on outcomes of 67 single auto-HSCTs performed from 2017 to 2021. Responses as well as progression-free (PFS) and overall survival (OS) rates were compared in MM patients per IWMG criteria in pre- and post-transplant periods. Three conditioning regimens were assigned: melphalan 200 mg/m2 (Mel200), melphalan/carfilzomib combination (Mel/Karfil), and melphalan/thiotepa combination (Mel/Thio). In an additional cohort of 12 MM patients, next-generation sequencing assay was used to detect inherited and somatic mutations associated with proteasome inhibitor efficacy. For this purpose, DNA of peripheral blood lymphocytes and bone marrow plasma cells were examined. Results. PFS medians were comparable in MM patients treated with Mel200 (n = 40) and Mel/Karfil (n = 10) conditioning regimens, they were 32 and 23 months, respectively (p = 0.241). In these cohorts, OS median was not reached, and the curves showed no significant differences (p = 0.050). Out of 10 MM patients treated with Mel/Karfil, six received melphalan 140 mg/m2, the remaining 4 patients received 200 mg/m2. Complete response (CR) rate in the Mel200 and Mel/Karfil groups increased two-fold after auto-HSCT: from 35.5 % to 74.2 % and from 25.0 % to 50.0 %, respectively. The worst PFS and OS medians were in the Mel/Thio group, i.e., 12 and 17 months, respectively, and CR rate after auto-HSCT remained unchanged. The best PFS was associated with CR rather than very good partial or partial response after auto-HSCT, they were 48, 21, and 23 months, respectively (p = 0.001). Exome sequencing of DNA of peripheral blood lymphocytes and bone marrow plasma cells revealed polymorphic variants in the genes associated with chemotherapy response. Conclusion. The outcomes of Mel/Karfil, the regimen containing the reduced dose of melphalan 140 mg/m2, and the statistical comparability with the Mel200 regimen suggest that this combination can be effective in the treatment of MM patients with impaired renal function, which still needs to be further confirmed. No advantage of the combined conditioning regimen over the standard one can be accounted for by the loss of plasma cell sensitivity to proteasome inhibitors. The obtained data provide ground for modifying the study protocol with a particular focus on evaluating the efficacy and safety of conditioning regimen Mel/Karfil with melphalan 200 mg/m2 depending on biologic phenotype of plasma cell.

Aim. To compare toxicity and efficacy of high-dose melphalan chemotherapy with subsequent autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients aged under and over 60 years. Materials & Methods. The retrospective analysis was conducted on the data of 107 MM patients, 78 of them were aged under 60 years (median 54 years), and 29 of them were aged 61 years and older (median 63 years). All patients received auto-HSCT in the period of 2017–2022. Single and tandem auto-HSCT were performed in 92 and 15 patients, respectively. Patients with tandem auto-HSCT (n = 15), lost to follow-up patients (n = 8), and patients who died during early post-transplant period (n = 4) were excluded from survival analysis. Survival rates were calculated based on the date of auto-HSCT. Results. A comparative evaluation of the results in two age groups showed a significant difference in the number of patients treated with ixazomib during the induction period (р = 0.019) and cyclophosphamide 3 g/m2 as part of auto-HSC mobilization (р = 0.014), as well as 200 or 140 mg/m2 melphalan as part of conditioning regimen (р = 0.039 and р = 0.009, respectively). With a follow-up median of 13 months (range 1–57 months), the median progression-free survival in the groups ≤ 60 years vs. > 60 years was 32 and 47 months, respectively (hazard ratio [HR] 0.688; 95% confidence interval [95% CI] 0.270–1.754; p = 0.704). The median overall survival in patients aged under 60 years appeared to be 57 months, it was not reached in patients aged 61 years and older (HR 0.689; 95% CI 0.169–2.803; р = 0.577). Conclusion. The results of the study suggest that all newly diagnosed MM patients aged under 70 years should be regarded as being eligible for auto-HSCT.

Aplastic anemia (AA) is a non-neoplastic hematological disease closely associated with bone marrow failure which is typical of paroxysmal nocturnal hemoglobinuria (PNH) and myelodysplastic syndrome (MDS). The PNH clones can be detected in more than a half of AA patients at onset of the disease, and there is a probability for AA/PNH co-variants to progress to classic hemolytic PNH. At the same time, the AA patients treated by immunosuppressive therapy undergo the risk of disease transformation to MDS and acute myeloid leukemia. Currently known risk factors and possible precursors of such transformation are considered in the brief literature review. In addition to that, the paper provides a case report of AA/PNH transformation to MDS during complete AA remission after immunosuppressive therapy combined with a successful haploidentical transplantation of hematopoietic stem cells.

Апластическая анемия (АА) — неопухолевое заболевание системы крови, имеющее тесную связь с заболеваниями, характеризующимися костномозговой недостаточностью, такими как пароксизмальная ночная гемоглобинурия (ПНГ) и миелодиспластический синдром (МДС). Клоны ПНГ могут быть выявлены более чем у половины больных АА в дебюте заболевания, и существует вероятность перехода сочетанных вариантов АА/ПНГ в классическую гемолитическую ПНГ. В то же время у пациентов с АА, получавших курсы иммуносупрессивной терапии, имеется риск трансформации болезни в МДС и острый миелоидный лейкоз. Известные к настоящему времени факторы риска и возможные предвестники такой трансформации рассматриваются в кратком обзоре литературы. Кроме того, представлено клиническое наблюдение трансформации АА/ПНГ в МДС на фоне полной ремиссии АА после проведения комбинированной иммуносупрессивной терапии с успешной гаплоидентичной трансплантацией гемопоэтических стволовых клеток.

Aim. To assess the rate of cases without antitumor response quality improvement after high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM). To assess the rate of allelic variants of IL1B, IL6, IL10, TNF genes and the status of hematopoietic niche cells as potential predictors of au-to-HSCT efficacy. Materials & Methods. A retrospective analysis was based on the data of 84 MM patients who received 112 auto-HSCTs, including 84 first and 28 repeated courses. Response variants were estimated according to IWG criteria. Molecular profiling of IL1B, IL6, IL10, and TNF genes was performed using polymerase chain reaction (PCR) with subsequent analysis of restriction fragment length polymorphism of PCR products. To analyze the status of hematopoietic niche cells histological, immunohistochemical, and morphometric methods were applied. Results. The first auto-HSCT yielded response quality improvement in 29 (54.7 %) out of 84 patients. The rate of complete response was significantly higher in patients who showed very good partial response before HDCT with au-to-HSCT, than in patients with partial response (PR), i.e., 57.9 % and 18.2 %, respectively (p = 0.005). No differences were identified in the groups of patients with other clinical and hematological parameters. After the second auto-HSCT in 4 out of 6 patients with PR the response variant did not change. A significant decrease of MM activity was associated with IL6 (-174С) mutant allele carrier status of 81.3 % vs. 41.6 % in the group with the unchanged response variant (р = 0.05). Response quality improvement was also related to a large number of cells on the endosteum in histological specimens of bone marrow (p = 0.038). Conclusion. The carrier status of IL6 (-174С) pathologic allele as well as the number of cells on the endosteum in histological specimens of bone marrow can be regarded as predictors of response quality improvement or lack thereof in MM patients after auto-HSCT.

Цель. Определить частоту случаев без улучшения качества противоопухолевого ответа после высокодозной химиотерапии (ВДХТ) с трансплантацией аутологичных гемопоэтических стволовых клеток (аутоТГСК) при множественной миеломе (ММ). Оценить частоту аллельных вариантов в генах IL1B, IL6, IL10, TNF и статус клеток гемопоэтической ниши как возможных предикторов эффективности аутоТГСК. Материалы и методы. Проведен ретроспективный анализ данных 84 больных ММ, которым выполнено 112 аутоТГСК, в т. ч. 84 первых и 28 повторных. Вариант ответа оценивали по критериям IWG. Молекулярное профилирование генов IL1B, IL6, IL10 и TNF проводили методом полимеразной цепной реакции (ПЦР) с последующим анализом полиморфизма длин рестрикционных фрагментов продуктов ПЦР. Для анализа статуса клеток гемопоэтической ниши использовались гистологические, иммуногистохимические и морфометрические методы. Результаты. После первой аутоТГСК улучшение качества ответа было зафиксировано у 29 (54,7 %) из 84 больных. Частота полного ответа была значимо выше у пациентов с предшествующим ВДХТ с аутоТГСК очень хорошим частичным ответом, чем с частичным ответом (ЧО), — 57,9 и 18,2 % соответственно (р = 0,005). Различия в группах пациентов с другими клинико-гематологическими показателями не выявлены. После повторной аутоТГСК у 4 из 6 больных с ЧО вариант ответа не изменился. Значимое снижение активности ММ было связано с носительством мутантного аллеля –174С гена IL6 — 81,3 vs 41,6 % в группе без изменения варианта ответа (р = 0,05). Улучшение качества ответа было также сопряжено с большим количеством клеток на эндосте в гистологических препаратах костного мозга (р = 0,038). Заключение. Носительство патологического аллеля –174С гена IL6, а также количество клеток на эндосте в гистологических препаратах костного мозга могут рассматриваться как предикторы возможного улучшения качества ответа или отсутствия такового у больных ММ после выполнения аутоТГСК.