Мантийноклеточная лимфома (МКЛ) – агрессивная и тяжело поддающаяся терапии лимфома из зрелых В-лимфоцитов, характеризующаяся транслокацией t(11;14) (q13;q32) и гиперэкспрессией циклина D1. У большинства пациентов заболевание отличается прогрессирующим клиническим течением, требующим незамедлительного начала противоопухолевой терапии, однако наряду с агрессивными вариантами выявляются индолентные МКЛ с длительной выживаемостью и возможностью применения тактики «наблюдай и жди». Такое различие обусловливается наличием вторичных цито- и молекулярно-цитогенетических аберраций, выявляющихся в дополнение к высокоспецифической t(11;14)(q13;q32), которые усиливают онкогенный потенциал циклина D1, вовлекают в лимфомогенез гены, регулирующие клеточный цикл, апоптоз, репарацию поврежденной ДНК, таким образом способствуя увеличению нестабильности генома и дальнейшей злокачественной трансформации опухолевого клона. В настоящее время особое внимание уделяется изучению прогностического влияния изменений кариотипа и аберраций отдельных генов, таких как MYC/8q24 и ТР53/17р13, на выживаемость пациентов с МКЛ. В нашем исследовании мы оценили генетический профиль 117 пациентов с МКЛ для выявления прогностически значимых цитогенетических и молекулярно-генетических маркеров и их взаимосвязи с продолжительностью общей и безрецидивной выживаемости пациентов. Mantle cell lymphoma (MCL) is an aggressive and difficult to treat lymphoma of mature B-lymphocytes characterized by t(11;14)(q13;q32) translocation and overexpression of cyclin D1. In most cases, the disease is manifested by progressive use of therapy, requiring the expense of starting anticancer therapy, however, in combination with aggressive variants, indolent MCL with long-term survival and the possibility of "watch and wait" tactics are detected. This difference is due to the presence of secondary cytogenetic and molecular cytogenetic aberrations, which are revealed in addition to the highly specific translocation t(11;14)(q13;q32), which enhance the oncogenic potential of cyclin D1, involve genes that regulate the cell cycle, apoptosis, and repair in lymphomagenesis. damaged DNA, thus contributing to an increase in genome instability and further malignant transformation of the tumor clone. Currently, special attention is paid to the study of the prognostic impact of changes in the karyotype and aberrations of individual genes, such as MYC/8q24 and TP53/17p13, on the survival of patients with MCL. In our study, we assessed the genetic profile of 117 patients with MCL to identify prognostic cytogenetic and molecular genetic markers and their relationship with the duration of overall and disease-free survival of patients.

Mantle cell lymphoma (MCL) is a type of peripheral B-cell non-Hodgkin’s lymphoma characterized by constitutive cyclin D1 overexpression leading to cell-cycle dysregulation and disruption of DNA damage repair. Apart from the typical translocation t(11;14)(q13;q32) and more rare variants, such as t(2;11)(p11;q13) and t(11;22)(q13;q11), a considerable number of patients quite often show secondary molecular and chromosomal aberrations underlying heterogeneity of the clinical course of MCL. Among a wide range of molecular genetic abnormalities, particular attention during the last years has been concentrated on studying the so-called double-hit MCL within a subgroup of patients with translocations involving CCND1 and MYC genes. Double-hit MCL is distinguished with rapid progression and tumor generalization at the time of diagnosis. Poor prognosis and low survival rates in most MCL patients call for the fastest possible diagnosis. Morphological and immunohistochemical as well as genetic methods (standard cytogenetic technique and fluorescence in situ hybridization) contribute to improving the quality of evidence-based diagnosis. The results of comprehensive diagnostic studies optimize prognosis assessment and treatment decision making in clinic.

The method of storage of PBSCs without cryopreservation is equal to traditional method controlled freezing and can be used in hospitals which have no Cryobank.

Assessment of the role of genetic abnormalities and minimal residual disease (MRD) is an active developing area in hematology. The use of genetic methods makes it possible to predict the course of the disease and apply an individualized approach to antimyeloma therapy. At the same time, the identification of MRD after therapy determines possibility of relapse. Aim. To identify the prognostic potential of MRD in patients in the standard and high molecular risk groups. Materials and methods. We analyzed 72 patients with MM (median age was 59 years (range 37-80), male/female - 1.3:1). All patients received initial therapy with proteasome inhibitors and / or immunomodulators. High dose therapy (MEL200) and autologous stem cell transplantation (ASCT) was carried out 50 (69%) patients. Standard cytogenetic and FISH methods were used to stratify patients in risk groups of mSMART 3.0. The standard risk (SR) was established in 52 (72%) patients, the high risk (HR) - in 20 (28%) patients. The MFC MRD status of bone marrow was evaluated after 4-6 cycles of induction therapy or after ASCT with use of 5-colors flow cytometry. MRD-negative status (MRD-) was based on level of clonal plasma cells <10-4 in bone marrow sample. Results. The MRD- was reached in 36% (26/72) patients. The median of OS in MRD+ group was 104 months, in MRD- was 146 months (p=.01). The median of PFS in MRD+ group was 26 months, in MRD- was 70 months (p=.00021). 2-years PFS in MRD+ group was 56%, in MRD- group was 100% (p=.00021). We divided patients into the following groups for evaluation the effect of MRD on survival in risk groups: SR МRD+ 34/72 (47%), SR МRD- 18/72 (25%), HR МRD+ 12/72 (17%) and HR MFC МRD- 8/72 (11%). The median of OS in HR MRD+ group was 72 months, in SR MRD+ - 104 months, in HR MRD- - 146 months, in SR MRD- was not achieved (p=.02). The median of PFS in HR MRD+ group was 24 months, in SR MRD+ - 26 months, in HR MRD- - 68 months, in SR MRD- - 70 months (p=.003). The 2-years PFS in HR MRD+ group was 44%, in SR MRD+ group was 50% and in SR MRD- and HR MRD- groups were 100% (p=.003). Conclusion. The absence of MRD is the most important prognostic factor. The leveling of negative effect of genetic abnormalities become possible when the MRD-negative response status is achieved. Presumably, this is due to the elimination of clonal plasma cells owing to the use of optimal antimyeloma therapy which is based on the risk stratification. Disclosures Martynkevich: Pfizer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Shuvaev:Novartis: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau.

Background: Bone marrow (peripheral blood stem cells (PBSCs)) autologous transplantation is the standard care for transplant-eligible patients with multiple myeloma. This treatment option is somewhat limited due to the high consumption of economic resources and the access to Cryobank. We performed a retrospective analysis of multiple myeloma patients who underwent autologous transplantation using non-cryopreserved and сryopreserved grafts at our institution from March 2016 to April 2020. Aim: Compare the results of autologous transplantation using non-cryopreserved and cryopreserved hematopoietic stem cells (HSC). Methods: 78 patients with MM were included in the study (male/female ratio 1.3:1). All patients got the standard immunochemotherapy programs. They had remission (≥partial response) till the auto-HSCT. Patients were divided in two groups depending on the technique of HSC storage: non-CRYO (n=35) and CRYO (n=43). Cryopreservation is a standard method of storage of HSC suspension. In our work we used the native HSC suspension which was saved from +4 °C to +6 °C during 72 - 120 hours. An effectivity and safety were evaluated in such parameters as the number of CD34+ and 7AAD- cells, colony-forming ability (CFA). All of these were made after apheresis and before reinfusion of HSC. Also, we compared the duration of hematopoiesis's recovery, the number of platelet transfusions, the length of hospitalization after auto-HSCT. Additionally, the effectiveness of therapy was assessed according to the IMWG response criteria and the level of residual tumor load before SCT and on day +100. Results : There were no differences in the total number of CD34 + cells x 106/kg, or in the level of 7AAD- cells, or in the total CFA. However, there was a significant difference in the percentage of loss of CD34+ cells from the moment of apheresis to the moment of reinfusion. We suppose it was caused adverse effects by temperature changes in CRYO group. In both groups, there were no severe infusion reactions on day 0. The adverse events (nausea, vomiting, tachycardia, increased total bilirubin and indicator liver enzymes) were absent in the non-CRYO group. But 29/43 (67.4%) patients had such symptoms in the CRYO group on day 0. The results are presented in the comparison table (image 1) of the evaluated parameters. All patients had full recovery of hematopoiesis till discharge from the hospital. Neutrophil recovery was achieved at 11th day (range 9-14) and platelets at 12th day (range 8-19) in the non-CRYO group, and 10th day (range 8-14) and 12th day (range 8 -20) in the CRYO group, respectively. The frequency of achieving a partial response before autoHSCT was 37% (13/35), a very good partial response - 40% (14/35), a complete response - 23% (8/35) in the non-CRYO group and 72% (31/43), 14% (6/43) and 14% (6/43) in the CRIO group, respectively. HSCT was improved the efficiency of treatment as well as the frequency of complete and MRD-negative responses in both groups. Partial response after autoHSCT was achieved in 23% (8/35) patients, very good partial response in 40% (14/35), complete response in 37% (13/35) in the non-CRYO group compared to the CRYO group (47% (20/43), 21% (9/43) and 32% (14/43), respectively). The MRD status was assessed before and after autoHSCT in 48 patients. The frequency of MRD-negative response before autoHSCT was 8.7% (2/23), after transplantation - 21.7% (5/23) in the non-CRYO group and 4% (1/25) and 12% (3/25) in the CRYO group, respectively. AutoHSCT was increased the "depth" of the response in 25 patients. However, there were no significant differences between the same-type categories in the non-CRYO and CRYO groups (p>.05). AutoHSCT led to decrease of tumor load (TL). The average TL value was 0.55% before HSCT and 0.018% after HSCT (p=.036) in the non-CRYO group and 2.05 and 0.37 (p=.003) in the CRYO group, respectively. The mean TL after HSCT in the non-CRYO (0.018%) was smaller than mean TL in the CRYO (0.37%) groups (p <.05). Conclusion: The method of storage of PBSCs without cryopreserved is equal to traditional method controlled freezing with Dimethyl sulfoxide and can be used in hospitals which have no a Cryobank in their composition. Table Disclosures Shuvaev: Novartis: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau.

Abstract Introduction. Most patients with multiple myeloma (MM) are considered to be incurable, and relapse owing to minimal residual disease (MRD) is the main cause of death among these patients, the optimal methodology to assess MRD is not clear. The results of previous studies demonstrated the potential of multiparameter flow cytometry (MFC) and (PET-CT) in evaluation of MRD in MM. MRD monitoring should be applied in prospective clinical trials to compare and evaluate the efficacy of different treatment strategies, particularly in the consolidation and maintenance settings. The impact of MRD negativity is important, but further studies are needed to quantify the pharmacoeconomic and quality-of-life differences between early and delayed transplant strategies. Therefore, with the currently available evidence, upfront autologous stem cell transplantation (ASCT) is standard of care regardless of MRD status. Aim. We are aiming to determine the role of MRD and role of autologous stem cells transplantation in MM. Materials and methods. We`ve recently started a prospective one-center pilot study in subjects with MM. We analyzed 18 transplant-eligible patients with MM (the median age is 57 years, a male/female ratio is 3.5:1).The induction therapy Bortezomib-based only regimens was used in 12/18 (67%) patients, combination of Bortezomib-Immunomodulator-based regimens - in 6/18 (33%). High dose therapy (Mel200) and ASCT is carried out on 100% patients. The standard risk was established on 15 patients, 1 patient has an intermediate risk and 2 patients have high risk according to mSMART 2.0 stratification. The MFC MRD status of bone marrow was evaluated after 4-6 cycles of induction therapy and after ASCT on 5-color flow cytometry with use anti- CD38, CD138, CD45, CD19, CD20, CD27, CD56 and CD117 antibodies. We were based on two levels: MFC MRD- (<10-4) and MFC MRD- (<10-5) for assessing the significance of factors that affect MRD and for identifying the prognostic potential of MRD-negative status. The evaluation of MRD was carried out by genetic (cytogenetic and FISH) analysis of bone marrow plasma cells and PET-CT with 18-FDG before ASCT and on 100 day post ASCT. The results. The MFC MRD- (<10-4) before carrying out an ASCT reached 22.2% (4/18), the MFC MRD- (<10-5) - 0% and was not depended on the variant of pre-transplantation regimen. After the ASCT had been carried out there was a tendency to decrease the tumor burden in bone marrow from 0.65% to 0.1% and to increase the frequency of MFC MRD- (<10-4) status to 44.4% (8/18), of which MFC MRD- (<10-5) was 16.7% (3/18). MRD status was determined before ASCT and after ASCT by MFC and FISH in patients with high risk. The use of maintenance therapy with bortezomib (n = 5) or lenalidomide (n = 13) did not increase the frequency of MRD status. The PFS median in MFC MRD+ (>10-4) group was 23 months, in the MFC MRD- (<10-4) was not achieved; 2-year PFS was 43% and 100%, respectively (p=.04) We compared PFC between MFC MRD+ (>10-4) before ASCT (n = 4) and MFC MRD- (<10-4) after ASCT (n = 6) to assess the effect of ASCT in MM. The median PFS was not reached in both groups; 2-year PFS was 67% and 100%, respectively. The reliable difference between PFS in MFC MRD- (10-4-10-5) group and MFC MRD- (<10-5) was absent: the median of PFS was not achieved in both groups. PET-CT has been tested on 15 patients, PET-CT- response was achieved in 53% (8/15) patients. The PFS median in PET-CT+ group and PET-CT- group was not achieved. The 2-year PFS was higher in PET-CT+ group then PET-CT- probably due to patients with MFC MRD-. The 2-year PFS in «MFC MRD-PET-CT-» group was 100% to 55% in other patients. Conclusion. Carrying out ASCT demonstrated a tendency to increase the percentage of MFC MRD negative responses and improvement of PFS. The use of MFC in evaluation of MRD should be complemented with PET-CT and genetic methods for further analysis of the MFC MRD role status on MM patients. Disclosures No relevant conflicts of interest to declare.