Background. Mantle cell lymphoma (MCL) accounts for 3–10 % of all cases of non-Hodgkin lymphoma and is known for its aggressive course with frequent relapses and the presence of extranodal lesions. With the introduction of more effective systemic therapy and increasing patient life expectancy, the frequency of relapses with central nervous system (CNS) involvement has increased to 4–20 %. Despite the use of targeted drugs, the prognosis for patients with CNS involvement remains inadequate.

Aim. To identify the incidence rate and evaluate the effectiveness of possible therapeutic approaches in the treatment of CNS lesions in patients with mantle cell lymphoma.

Materials & methods. The study included 67 patients with MCL, with a median age of 63. The therapy efficacy was assessed depending on the initial treatment option, including immunochemotherapy, high-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT), and Bruton's tyrosine kinase (BTK) inhibitors. This article describes a series of clinical cases of CNS-relapsed MCL that achieved a complete response to ibrutinib treatment, even after auto-HSCT, and a literature review of the options of using targeted drugs in MCL relapsing at the CNS.

Results. The median follow-up was 40 months. The frequency of t(11;14) was 74 %, and aberrations of chromosome 17 – 9 %. The best objective response rate was noted in the subgroups of auto-HSCT and BTK inhibitors, which reached 100 %. Disease progression was observed in 57 % of patients, with the lowest frequency in patients who received auto-HSCT (25 %). In second-line treatment, BTK inhibitors demonstrated high efficacy, with a 3-year overall survival rate of 100 %. The incidence of CNS involvement in relapsed MCL was 8 % (3/37). Relapse with CNS involvement was an adverse prognostic factor, HR = 47.3 (95 % CI 4.1–543.3), p = 0.002.

Conclusion. BTK inhibitors demonstrated high efficacy in treating MCL, especially in elderly patients. Despite the lack of statistically significant differences, BTK inhibitors (mainly ibrutinib) have shown excellent results in first- and second-line treatment lines. Due to its ability to penetrate the blood-brain barrier, ibrutinib can be used in patients with CNS involvement.

Background. Renal failure is a common complication of MM, and it is often associated with a poor prognosis. AutoSCT is a standard therapy for young patients, but it is usually avoided in a group of patients with dialysis-dependent nephropathy because of possible higher toxicity, associated with required high dose chemotherapy.

Aim. to evaluate the efficacy and safety of autoSCT in patients with dialysis-dependent nephropathy by analyzing our own experience

Methods. During 2015-2022 14 patients with dialysis-dependent MM underwent AutoSCT in MCH №52: 8 male and 6 female; median age was 53 years (43-66). 2 of them got tandem transplant procedure. According to ISS criteria, 11 (78%) patients had stage III, 1 – stage II. Cytogenetic bone marrow investigation has been conducted in 9 patients, 2 of them had high-risk cytogenetic abnormalities.
Induction therapy was performed with standard protocols: 8 patients were treated by 1 line therapy courses (6 – VCD, 2 – VRD), 6 patients got 2 line therapy. By the end if induction chemotherapy 5 patients reached CR, 5 –VGPR, 4 – PR. Hematopoietic stem cell mobilization was performed by Cyclophosphamide 3 g/m2   followed by G-CSF 5 mkg/kg. All SC apheresis were effective, 1 patient got additional chemomobilization by high-dose etoposide. Melphalan 140 mg/m2  was used as pre-transplant conditioning in 10 pts (78%), in 3 cases Bendamustine 200mg/m2 was added to Melphalan (-1 day). Mean account of transfused CD34+ cells was 3,61х10^6.

Results.  Mean engraftment period was comparable to patients without renal failure.  AutoSCTs were accompanied with following infectious complications: febrile neutropenia (100%), mucositis 3-4 st (71%), necrotic enteropathy - (64%), pneumonia (21%), bacteremia (50%). HSV 1,2; HV 6 and CMV reactivation was proved in 4 pts (29%). The patients also had following non-infectious complications: gastrointestinal bleeding – 1 pt, toxic cardiomyopathy – 1 pt. 100 day TRM was 0%.
According to the results of control investigation on +100 day after autoSCT all the patients had deeper response: 11 (79%) reached CR, 2 (14%) – VGPR, 1(7%) – PR.  8 pts (57%) showed renal response and became independent of dialysis. Long –term outcome (median follow up was 41 months (6-76): 7 (50%) pts remain CR, 3 pts (21%) relapsed early, 2 of them died on progression. 1 patient died because of hemorrhagic stroke after 12 months after autoSCT. 3 pts (21%) had late relapse. 8 (57%) remain dialysis-independency (1 of them underwent kidney transplantation). Median overall survival has not been reached. Three-year OS was 78%. Three-year progressive-free survival was 50%.

Conclusion.  AutoSCT (including tandem) could be performed as consolidation therapy in patients with MM and dialysis-dependent nephropathy. AutoSCT is a chance to improve renal response and become dialysis independent, even if it has not reached during induction therapy.

Диффузная В-крупноклеточная лимфома является биологически крайне гетерогенной группой опухолей лимфоидной природы. Рекомендованный стандарт первой линии терапии R-CHOP сохраняет лидирующую позицию при лечении впервые диагностированной ДВКЛ. При этом результаты унифицированного подхода к терапии, не учитывающего высокую степень молекулярно-генетической гетерогенности данного типа лимфомы, признаются неудовлетворительными.
Нами впервые в Российской Федерации представлено клиническое наблюдение, в котором описывается опыт применения комбинации базисной терапии и противоопухолевого агента акалабрутиниба на основании результатов таргетного секвенирования.