Oncohematology

Aim. To evaluate and compare the efficacy of daratumumab as monotherapy and in combination with other drugs in patients with relapsed / refractory multiple myeloma depending on the previous therapy lines number.

Materials and methods. The study included 97 patients with relapsed / refractory multiple myeloma with a median age of 63 (33–79) years. Daratumumab monotherapy was administered to 71 patients, 11 patients received Dara-Rd (daratumumab + lenalidomide + dexamethasone), 10 – Dara-Pd (daratumumab + pomalidomide + dexamethasone). Dara-Kd (daratumumab + carfilzomib + dexamethasone) therapy was administered to 5 patients. Daratumumab as monotherapy was received by 21 patients in the 2^nd line of therapy, 28 in the 3^rd line, 12 in the 4^th line, and 10 in the 5^th line or more.

Results. The 2-year overall survival of 71 patients receiving daratumumab monotherapy was 71.7 %; 2-year progression-free survival was 59.5 %. Objective response, including complete, very good partial and partial response, was observed in 45.0 % of patients. An objective response with the Dara-Rd regimen was observed in 54.6 % of patients. Median progression-free survival was not achieved with a median follow-up of 26 months. The use of Dara-Pd allowed to achieve an objective response in 70 % of patients. The median progression-free survival was not achieved, the median follow-up was 17 months. An objective response during Dara-Kd therapy was obtained in 20 % of patients, the median follow-up was 18 months.

Ten (47.6 %) patients out of 21 who received daratumumab monotherapy in the 2^nd therapy line achieved an objective response. The median progression-free survival was not achieved, the median follow-up was 13 months. Of the 28 patients who received daratumumab in the 3^rd therapy line, an objective response was achieved in 10 (35.7 %); the median follow-up was 17 months. Patients who received daratumumab in the 4^th therapy line achieved an objective response in 66.7 % of cases. The median progression-free survival was 18 months, the median overall survival was not achieved, and the median follow-up was 21 months. In patients who received daratumumab in the 5^th or more therapy lines, an objective response was achieved in 40.0 % of cases. The median progression-free survival was not achieved, the median follow-up was 21 months.

Conclusion. The use of daratumumab in combination with other antitumor drugs and as monotherapy is one of the optimal treatment options for patients who have received two or more therapy lines.

Background. Current approaches to the treating BCR::ABL1-negative B-cell lymphoblastic leukemia (B-ALL) patients are aimed at incorporating targeted agents into chemotherapy regimens to improve the efficacy of the first-line therapy. Rituximab was one of the first such drugs to be used and shown to improve survival in B-cell lymphoproliferative disorders. Its inclusion in treatment regimens for BCR::ABL1-negative B-ALL remains controversial.

Aim. To determine the prognostic value of CD20 expression on tumor cells in adult patients with BCR::ABL1-negative B-ALL treated according to the ALL-2016 protocol.

Materials and methods. The study included 143 patients with BCR::ABL1-negative B-ALL who received treatment from December 2016 to February 2024 as part of the multicenter RALL-2016 trial (ClinicalTrials.gov, NCT03462095). The median patient age was 30 (18–55) years, with a male: female ratio of 71 (50 %):72 (50 %). Immunophenotyping of bone marrow blast cells using flow cytometry was performed in all patients at the disease onset. The presence of the CD20 marker on tumor cells was considered positive if its expression was ≥20 %. From September 2024 to September 2025, four patients received treatment according to the R-RALL-2016m protocol (ALL-2016m including rituximab).

Results. In the RALL-2016 study, the frequency of CD20 expression in BCR::ABL1-negative B-ALL was 37 % (53 of 143). Five-year overall survival in BCR::ABL1-negative B-ALL with CD20 expression was 73 %, compared to 68 % in patients negative for this marker (p = 0.9405). Three-year relapse-free survival was 73 and 70 % in the presence and absence of CD20 expression, respectively (p = 0.7944). All patients (4 of 4) achieved bone marrow remission after phase I induction therapy according to the R-RALL-2016m protocol, and 75 % achieved negative minimal residual disease status at the end of induction therapy.

Conclusion. In adult patients with BCR::ABL1-negative B-ALL, the inclusion of rituximab may improve long-term survival outcomes by more rapidly achieving clinical and hematological remission and increasing the rate of minimal residual disease negativity after induction therapy. Continued follow-up of patients receiving the new protocol is needed to assess the likelihood of late complications and long-term outcomes.

Background. Therapeutic options for patients with relapsed multiple myeloma (MM) after primary autologous hematopoietic stem cell transplantation (auto-HSCT) may include not only modern targeted therapies but also second auto-HSCT.

Aim. To evaluate the efficacy of second auto-HSCT in the treatment of the first MM relapse, to identify prognostic factors influencing progression-free survival (PFS) and overall survival (OS), and to compare the early post-transplantation period following primary and second auto-HSCT.

Materials and methods. This retrospective study included 23 patients (13 men and 10 women, median age 52 years) with MM who underwent primary auto-HSCT as consolidation after induction therapy and second auto-HSCT during the treatment of their first disease relapse. The effect of second auto-HSCT was assessed based on PFS and OS. In addition, the analysis of results also considered the PFS from primary auto-HSCT to the first relapse / disease progression.

Results. The median PFS after second auto-HSCT was 26 months. Survival outcomes were significantly better in patients with a PFS of more than 18 months after primary auto-HSCT compared to those with a PFS of less than 18 months (median 32 months vs 9 months).

Overall survival outcomes after second auto-HSCT were highly encouraging: the median OS was 75 months, with 3-year survival reaching 82 % and 6-year survival – 70 %.

Second auto-HSCT was not associated with a higher risk of infectious complications in the early post-transplant period or a prolonged recovery of blood count parameters compared to primary auto-HSCT.

Conclusion. Based on our results and literature data, second auto-HSCT can be safely performed in most MM patients who have relapsed after primary auto-HSCT.

Acute lymphoblastic leukemia (ALL) in children and adolescents is one of high curable malignancy with long-term survival rate 91 %. Nevertheless, patients with high risk of relapse / refractory ALL have event-free survival not exceed 55 %. For therapeutic efficacy improvement in patients with high risk ALL, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is used.

Improvement of ALL therapy by targeted and molecular oriented drugs (imatinib mesylate, dasatinib, blinatumomab, inotuzumab ozogamycin), extension of therapeutic options for patient care in the post-transplant period are changed indications for allo-HSCT.

In the current issue a modern indications for allo-HSCT in patients with primary diagnosed ALL, based on cytogenetic, molecular biologic, and clinical characteristics by the leading research groups AIEOP / BFM (Italy / Germany), St. Jude (USA), COG (USA) are presented. In spite of presented differences, common indications for allo-HSCT are minimal residual disease persistence in postinduction period in combination with cytogenetic, molecular and biologic factors of unfavorable prognosis.

Background. Multiple myeloma (MM) is a genetically complex disease in which different aberrations can be determined in tumors of different localizations. The impact of mutations in the RAS-ERK pathway genes on the MM course, despite numerous publications, is unclear.

Aim. To evaluate mutations in the KRAS, NRAS, BRAF genes in plasma free circulating tumor DNA and CD138⁺ bone marrow cells and to analyze therapy results of MM patients at different stages depending on MAP kinase genes mutational status.

Materials and methods. A prospective single-center study from September 2021 to December 2024 included 100 patients (45 men and 55 women) with newly diagnosed MM aged 29 to 83 years (median 55 years), 41 patients without plasmacytomas and 59 with plasmacytomas. The diagnosis was established in accordance with International Myeloma Working Group – 2014 criteria. Induction therapy was performed according to bortezomib-containing programs; the antitumor response was assessed according to International Myeloma Working Group – 2016 criteria. Analysis of KRAS, NRAS, BRAF genes mutations on DNA samples of CD138⁺ bone marrow cells was performed in all patients, in free circulating tumor DNA – in 81 patients. Statistical analysis was performed using the MedCalc program, and the Fisher criterion was also used. Survival analysis was performed using the Kaplan–Meier method, with statistical significance assessed using the log-rank test.

Results. The frequency of KRAS, NRAS, BRAF genes mutations in free circulating tumor DNA and / or bone marrow in the total group was 50 %. The detection frequency of MAP kinase genes mutations in patients with and without plasmacytomas was comparable. No differences in detection frequency of high-risk cytogenetic aberrations were found in groups of patients with RAS-ERK pathway genes mutations and without them. A tendency towards a lower frequency of achieving complete remission after induction therapy was noted in patients with mutated gene status compared to patients without MAP kinase genes mutations (17 % versus 41 %; p = 0.07). At control time points after auto-transplantation, the trend remained: patients with MAP kinase genes mutations achieved a deep antitumor response 2 times less often compared to patients without mutations (30 % versus 59.5 %; p = 0.051). The probability of two-year progression-free survival of patients with MAP kinase genes mutations was significantly lower (p <0.05) – 62 % versus 92 % for patients without KRAS, NRAS, BRAF genes mutations.

Conclusion. Due to the complex genetic structure and spatial anatomical heterogeneity of MM, the study of various localization tumors is extremely relevant. When mutations in the MAP kinase genes are detected, the antitumor response at various therapy stages is worse, and the probability of progression-free survival is significantly lower than in patients without mutations in these genes.

Background. Kidney dysfunction is a common manifestation of multiple myeloma (MM). Kidney damage in MM is most often associated with cast nephropathy; however, rarer forms such as light chain deposition disease (LCDD) and C3 glomerulopathy (C3 GP) also occur. According to several studies, patients with these forms of kidney damage more frequently develop end-stage renal disease and have a worse prognosis for kidney function recovery.

Aim. To evaluate the efficacy of induction therapy with targeted drugs followed by consolidation with high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with MM and nephropathy associated with LCDD and C3 GP.

Materials and methods. Medical data from 3 patients with MM and nephropathy caused by LCDD (2 cases) and C3 GP (1 case) who received induction therapy followed by auto-HSCT were retrospectively analyzed.

Results. At disease onset, impaired kidney function with reduced glomerular filtration rate was detected in all 3 patients; 1 case presented with anuria. All patients received renal replacement therapy. After induction, complete hematologic response was achieved in 2 patients and very good partial response in 1 patient with MM and C3 GP. Renal replacement therapy was discontinued in 2 out of 3 cases. On the 100^th day after auto-HSCT, hematologic complete response persisted in 2 patients with LCDD; in the C3 GP case, the response deepened to stringent complete response. All patients achieved renal response, with no need for renal replacement therapy. During long-term follow-up (23–82 months), 1 patient maintained the achieved response, while 2 patients relapsed at 2.5 and 2 years post-auto-HSCT, respectively.

Conclusion. Multiple myeloma patients with LCDD- or C3 GP-associated nephropathy exhibit severe kidney dysfunction, often requiring renal replacement therapy, necessitating thorough evaluation in the absence of typical cast nephropathy features. Comprehensive therapy including auto-HSCT in young, fit MM patients with LCDD- or C3 GP-associated nephropathy enables deep hematologic response and improves renal function.

Nikolay Konstantinovich Goryaev (1875–1943) is recognized as an accomplished clinician and scientist who established fundamental principles in the field of hematology. His research focused on hematological disorders, in particular acute lymphoblastic leukemia, polycythemia, and splenopathies, as well as detailed investigations into the microanatomy and innervation of the spleen. He created the Goryaev chamber, a specialized device designed to facilitate the standardized counting of blood cells using a defined grid. Moreover, professor Goryaev founded a significant clinical school, mentoring numerous prominent specialists including V. I. Katerov, R. M. Akhrem-Akhremovich, I. I. Tsvetkov, P. S. Poptsova, S. I. Sherman, K. A. Dryagin, and others. Professor Goryaev was known for his attributes of integrity, diligence, empathy, and ethical conduct. He was consistently remembered with respect by his peers and former students.

This article will explore professor Goryaev’s personal attributes, emphasizing their contribution to his professional achievements and his enduring influence within the medical community.