Актуальность. Трансплантация аутологичных гемопоэтических стволовых клеток (аутоТГСК) — обязательный этап лечения больных с впервые диагностированной множественной миеломой (ММ), которым по возрасту и соматическому статусу может быть проведена высокодозная химиотерапия с последующей аутоТГСК. Тем не менее вопрос о целесообразности выполнения двойной (тандемной) аутоТГСК остается нерешенным. Цель. Сравнительный анализ общей (ОВ) и выживаемости без прогрессирования (ВБП) у больных ММ после одной и двойной (тандемной) аутоТГСК в условиях реальной клинической практики. Материалы и методы. Проведен ретроспективный анализ данных 83 пациентов с ММ, распределенных в две группы: с одной (n = 41) и двойной (n = 42) аутоТГСК. Медиана возраста больных в 1-й и 2-й группах составила 58 (диапазон 42–68 лет) и 54 года (диапазон 40–65 лет) соответственно. Больных в возрасте 60 лет и старше было 16 (39 %) и 11 (26,2 %) в этих группах соответственно. Точкой отсчета при построении кривых выживаемости была дата выполнения первой (в группе 1) и повторной (в группе 2) аутоТГСК. Законченным событием при расчете ВБП была дата констатации прогрессирования или рецидива заболевания, включая биохимический в случае начала специфического лечения. Результаты. Общее число больных с очень хорошим частичным ответом и выше перед выполнением аутоТГСК в 1-й группе было 23 (56,1 %), во 2-й группе перед выполнением повторной аутоТГСК — 30 (71,4 %). Режим кондиционирования Mel200 использовался у 53,7 % больных 1-й группы. Во 2-й группе данный режим был приоритетным при проведении первой аутоТГСК (83,3 % больных) и реже назначался при повторной трансплантации (40,5 %). При медиане наблюдения 11 и 40,5 мес. в 1-й и 2-й группах не выявлено значимого различия в медиане ВБП (21 и 40 мес.; р = 0,154) и ОВ (медиана не достигнута в обеих группах; р = 0,882). Не обнаружено различий между группами по времени до развития рецидивов/прогрессирования заболевания и частоте ранних рецидивов. Заключение. Дополнительного противоопухолевого эффекта повторной аутоТГСК не выявлено. Возможные причины — отсутствие информации о хромосомных аберрациях в дебюте заболевания у основной части пациентов и немногочисленный состав групп. Тем не менее принято решение ограничить число тандемных аутоТГСК, оставляя повторную трансплантацию преимущественно на случаи поздних рецидивов/прогрессирования. Инициированы исследования по поиску предикторов, связанных с улучшением выживаемости больных ММ при проведении повторной (тандемной) аутоТГСК.

Background. Autologous hematopoietic stem cell transplantation (auto-HSCT) is an indispensable treatment stage in patients with newly diagnosed multiple myeloma (MM) who are, based on age and health status, eligible for high-dose chemotherapy with subsequent auto-HSCT. However, the issue of double (tandem) auto-HSCT feasibility remains unresolved. Aim. To compare overall survival (OS) and progression-free survival (PFS) in MM patients after single and double (tandem) auto-HSCTs in clinical practice. Materials & Methods. Retrospective analysis enrolled 83 MM patients divided into two groups: with single (n = 41) and double (n = 42) auto-HSCTs. Median age in groups 1 and 2 was 58 years (range 42-68) and 54 years (range 40-65), respectively. In these groups there were 16 (39 %) and 11 (26.2 %) patients > 60 years old. The reference point of survival curve was the date of first (in group 1) and 2nd (in group 2) auto-HSCTs. In PFS assessment, completed event was the date of disease progression or relapse detection, including the biochemical one in case of specific therapy onset. Results. Total number of patients with > very good partial response before receiving auto-HSCT in group 1 was 23 (56.1 %), and in group 2 before receiving 2nd auto-HSCT it was 30 (71.4 %). Mel200 conditioning was administered to 53.7 % of patients in group 1. In group 2 this conditioning regimen was a priority in performing first auto-HSCT (83.3 % of patients) and was more rarely used in case of repeated transplantation (40.5 %). With median follow-up of 11 and 40.5 months in groups 1 and 2 no significant differences were identified either in median PFS (21 and 40 months; p = 0.154) or in median OS (not reached in both groups; p = 0.882). No differences between groups with respect to the time before relapse/progression or early relapse rate were observed. Conclusion. Repeated auto-HSCT showed no additional antitumor effect. It can be accounted for by the lack of data on chromosome aberrations at the disease onset in most patients and by a small number of patients in the groups. Nevertheless, it was decided to limit the number of tandem auto-HSCTs and to perform 2nd transplantation mostly in case of late relapse/progression. New studies were initiated which will focus on the search of predictors associated with survival improvement in MM patients while performing double (tandem) auto-HSCTs.

Background. There exist different data on how the administration of granulocyte colony-stimulating factor (G-CSF) after autologous hematopoietic stem cell transplantation (auto-HSCT) affects the duration of post-transplantation agranulocytosis in multiple myeloma (MM) patients. Aim. To study the effect of G-CSF, administered after auto-HSCT to MM patients, on the duration of neutrophil engraft-ment, febrile neutropenia rate, and hospitalization duration. Materials & Methods. The trial included 36 MM patients aged 42-69 years (median 59 years), 16 of which were not treated with G-CSF (1st group), and 20 patients received a single injection of 6 mg pegylated G-CSF on Day +4 or Day +5 (2nd group). Results. Patients of the 1st group were significantly younger than patients of the 2nd group: median 55.5 and 61 years, respectively (p = 0.006). There were no differences with respect to the number of patients who previously received lenalidomide, the overall and very good partial response rate, the number of the first and repeated auto-HSCTs, and the number of melphalan conditioning regimens. The patients who received G-CSF engrafted neutrophils on day 11 (median) after auto-HSCT, i.e. earlier than patients without G-CSF administration who engrafted neutrophils on day 13 (p = 0.006). In the 1st group intravenous antibiotics were administered for a longer time than in the group with G-CSF: median 13 and 11 days, respectively (p = 0.04). In 2 patients from the group without G-CSF sepsis was diagnosed. G-CSF administration led to a shorter hospital stay: median 16 and 18 days in the 1st and 2nd groups, respectively (p = 0.08). There were no differences in the number of patients with febrile neutropenia. Conclusion. G-CSF administration improves the course of the post-transplantation period in MM patients. The final decision on the feasibility of G-CSF administration after auto-HSCT can be made after more clinical observations are available.

Актуальность. Данные о влиянии гранулоцитарного колониестимулирующего фактора (Г-КСФ), вводимого после трансплантации аутологичных гемопоэтических стволовых клеток (аутоТГСК), на длительность посттрансплантационного агранулоцитоза у больных множественной миеломой (ММ) различаются. Цель. Изучить влияние Г-КСФ, назначаемого после выполнения аутоТГСК больным ММ, на сроки приживления нейтрофилов, частоту эпизодов фебрильной нейтропении и длительность госпитализации. Материалы и методы. Проведен анализ данных 36 больных ММ в возрасте 42–69 лет (медиана 59 лет), из которых 16 не получали Г-КСФ (1-я группа) и 20 получали однократную инъекцию пегилированного Г-КСФ в дозе 6 мг в Д+4 или Д+5 (2-я группа). Результаты. Пациенты 1-й группы были статистически значимо моложе больных 2-й группы: медиана 55,5 и 61 год соответственно (p = 0,006). Различий по числу больных, ранее принимавших леналидомид, частоте полного и очень хорошего частичного ответов, количеству первой и повторной аутоТГСК и числу режимов кондиционирования с мелфаланом в монорежиме не было. Приживление нейтрофильного ростка наступало раньше при назначении Г-КСФ — на 11-й день (медиана) после аутоТГСК, а в группе без Г-КСФ — на 13-й день (p = 0,006). В 1-й группе период назначения внутривенных антибиотиков был длиннее, чем в группе с Г-КСФ: медиана 13 и 11 дней соответственно (p = 0,04). У 2 больных из группы без Г-КСФ был диагностирован сепсис. Назначение Г-КСФ способствовало укорочению сроков пребывания больного в стационаре: медиана 16 и 18 дней в 1-й и 2-й группах соответственно (p = 0,08). Различий в числе больных с эпизодами фебрильной нейтропении не было. Заключение. Назначение Г-КСФ улучшает течение посттрансплантационного периода у больных ММ. Окончательное решение вопроса о целесообразности введения Г-КСФ после аутоТГСК возможно при увеличении количества клинических наблюдений.

Background. In multiple myeloma (MM) treatment a single autologous hematopoietic stem cell transplantation (auto-HSCT) is preceded by conditioning regimens aimed at intensifying cytoreductive effect. In the course of ongoing search for combined conditioning regimens an attractive option proved to be thiotepa/melphalan combination. Aim. Data analysis of a pilot study of the efficacy of conditioning regimens including administration of two alkylating agents (thiotepa and melphalan) with subsequent auto-HSCT. Materials & Methods. 9 patients received 10 auto-HSCTs with conditioning regimen including administration of 250 mg/m2 of thiotepa on Day -5 and 140 mg/m2 of melphalan on Day -2. After auto-HSCT pegylated filgrastim was administered in 8 patients. Engraftment period was calculated on the basis of absolute neutrophil count ≥ 0,5 x 109/L and thrombocyte level ≥ 20 x 109/L. Regimen toxicity was assessed according to CTCAE v5.0. Survival rates were estimated by Kaplan-Meier curves. Results. The use of thiotepa did not require administration of any additional drugs. The incidence of mucositis and enteropathy of grade 1-2 was 100 % and 70 %, respectively. Pyrexia was reported in 7 auto-HSCTs. Pneumonia occurred in 1 patient. The infusion of 1-3 doses of platelet concentrate (median of 2 doses) was required in all patients except for one. Donor erythrocytes were transfused to 3 patients. Engraftment was reported in all patients within the period of 10-14 days. Median hospitalization duration from Day 0 to hospital discharge was 16 patient-days. After auto-HSCT the quality of response improved in 6 out of 9 patients. MM progression was reported in one patient with complex karyotype. Further follow-up showed progression in 2 patients. By December 2018 median follow-up of 9 patients from the date of auto-HSCT was 9 months (range 3-20 months), me dian progression-free survival was 17 months, median overall survival was not reached. Conclusion. Acceptable toxicity, improvement of response quality, and maintenance of it for up to 20 months allow to consider combined conditioning regimen Thio/Mel to be a possible alternative to the standard Mel200 regimen.

Background. The success of autologous hematopoietic stem cell transplantation (auto-HSCT) depends on the speed of transplant engraftment which in turn is affected by the count of harvested and infused hematopoietic stem cells (HSC). Aim. To identify predictors of auto-HSCT efficacy in multiple myeloma (MM) patients under introduction of new drugs at the phase of HSC induction and mobilization. Materials & Methods. The results of auto-transplant harvesting and engraftment were retrospectively analyzed in 75 MM patients during 112 auto-HSCTs. Auto-transplants were harvested using cyclophosphamide and vinorelbine combined with granulocyte colony-stimulating factor (G-CSF) without plerixafor. Conditioning regimen included melphalan 200 mg/m2 or 140 mg/m2, and combination of tiothepa with melphalan. All patients received subcutaneous injections of G-CSF in post-transplantation period. Transplant engraftment was assessed according to absolute neutrophil count of ≥ 0.5 x 109/L, and thrombocyte count of ≥ 20 x 109/L. Results. It is established that the predictors of a high CD34+ cell count in auto-transplant are a single previous induction regimen (p = 0.0315) and administration of cyclophosphamide in mobilization regimen (p = 0.0001). Transplant engraftment period is determined by auto-HSCT serial number and amount of infused CD34+ cells. Hematopoiesis regeneration after the second auto-HSCT was accelerated by more frequent use of Mel140 (p = 0.001). Conclusion. Auto-transplant quality and engraftment period in MM patients primarily depend on the efficacy of induction therapy and the intensity of HSC mobilization regimen. Therefore, induction therapy and mobilization regimen need to be tailored to an individual patient, MM prognostic variant, probability of response to standard induction regimens, and the number of planned auto-HSCTs.

Background. A prompt graft acceptance is essential for positive autologous hematopoietic stem cell transplantation (auto-HSCT) outcome in multiple myeloma patients (MM). Prompt and favourable hematopoietic regeneration is associated with CD34+ cell count in a transplant. Although the indicators of low autotransplant cellularity have been defined, the practical application of new drug products and HSC mobilization regimens strengthens the relevance of determining their influence on the transplant quality. Aim. To determine the factors that are associated with low efficacy of auto-HSCT in MM patients and to evaluate the impact of lenalidomide during induction period and of vinorelbine as a mobilization regimen on the prognosis. Materials & Methods. The authors performed a retrospective analysis of autotransplant collection results in 68 MM patients treated with two mobilization regimens: 3 g/m2 cyclophosphamide with granulocyte colony-stimulating factor (G-CSF) and 30 mg/m2 vinorelbine with G-CSF. Mobilization was aimed at collecting not less than 2-4 х 106 CD34+ cells per kg body mass. CD34+ cell count was determined by four-color analysis on the Cytomics FC 500 laser flow cytometer. Results. The analysis showed that age or MM immunochemical specificity were not associated with CD34+ cell count in the transplant. Prior lenalidomide treatment compared to therapy without immunomodulators (4.1 х 106/kg vs. 7.76 х 106/kg) tends to decrease CD34+ count (р = 0.066). Cyclophosphamide included into mobilization regimen compared to vinorelbine (3.96 х 106/kg vs. 6.8 х 106/kg) significantly increased CD34+ cell count (р = 0.022). Conclusion. The decrease of CD34+ cell count in the autotransplant of the MM patients treated with lenalidomide prior to auto-HSC collection, and a lower mobilization activity of vinorelbine provide a basis for a differentiated selection of mobilization regimens. Vinorelbine may be administered to patients with a single auto-HSCT, i.e. elderly people and patients with complete response. In case of substantial lena-lidomide treatment prior to auto-HSCT, intermediate-dose cyclophosphamide is preferred.

Aim. To establish correlation between CD34+ autologous hematopoietic stem cell (HSC) count and colony-forming units (CFU) in the same peripheral blood apheresis product samples before and after cryopreservation in multiple myeloma and lymphoma patients, and to assess clinical value of these parameters. Materials & Methods. Cell samples of peripheral blood cytapheresis product and cell cultures were studied before and after cryopreservation in 32 multiple myeloma and 25 lymphoma patients who underwent autologous HSC transplantation. The material was analyzed using culture technique and flow cytometry. Results. The paper provides information on the relationship between CD34+ HSC count obtained by flow cytometry, and CFU in cell culture obtained by cytapheresis of the same peripheral blood samples. A direct correlation was confirmed between CD34+ count and all the CFUs before and after cryopreservation in lymphoma patients. Correlation between CD34+ count and granulocyte-macrophage CFUs was revealed in multiple myeloma and lymphoma patients before cryopreservation. Conclusion. The parameter of colony-forming capacity used for the assessment of the functional HSC was shown to be equally reliable criterion for condition evaluation of autotransplant proliferative pool than CD34+ cells. Both methods should be applied for qualitative and quantitative evaluation of an autotransplant for multiple myeloma and lymphoma patients.

Aim. The aim of this paper is to evaluate the effectiveness of low dose cytarabine (Ara-C) combined with cladribine for the treatment of relapsed or refractory acute myeloid leukemia (AML) and to determine clinical and lab factors associated with response to the therapy. Methods. Data of 10 patients aged 26–58 years (median 48 years) were analyzed. The diagnoses were de novo AML (7 patients), secondary AML (sAML) (2 patients) and refractory anemia with excess of blasts (RAEB-2) (1 patient). Four patients had primary refractory AML. Relapse was diagnosed in 3 patients. The induction scheme 7+3 was ineffective in patient with RAEB-2. There was no response to any kind of therapy in sAML patients. The treatment scheme under trial consisted of Ara-C 10–15 mg/m2 subcutaneously twice a day for 1–14 days and cladribine 5 mg/m2 intravenously once a day for 1–5 days. The course was repeated in case of at least two-fold decrease in bone marrow blasts level in a punctate versus baseline. Medical examination and maintenance therapy were performed in accordance with protocols approved by the clinic. Results. According to the protocol, the patients received 1–2 courses. Response was achieved in 5 patients: 2 patients achieved complete response (CR) and 3 achieved partial response (PR). The most common complication was hematologic toxicity. All patients received transfusions of blood components. No lethal outcomes were observed within 8 weeks. The duration of the response was 2 to 3 months. During this period of time, allogeneic stem cell transplantation was performed in 2 patients with CR; however, in one patient, the conditioning regimen began at the same time with the increase in blast cell count in the bone marrow. The search for unrelated donors of hematopoietic stem cells for 2 patients with CR was begun. The distinct features of all