Introduction. The advent of tyrosine kinase inhibitors (TKIs) in clinical practice drastically improved prognosis in patients with chronic myeloid leukaemia (CML). Adverse events of the TKI therapy and its high financial burden warrant the trend to gradually abandon this treatment.

Aim. To assess the results of CML patient monitoring after the withdrawal of TKI therapy.

Patients and methods. This prospective study included 98 chronic phase CML patients satisfying the criteria: any receiving of TKI therapy for ≥3 years; deep molecular response (DMR, BCR-ABL ≤ 0.01 % IS) during ≥ 2 years. The withdrawal was followed by quantitative BCR-ABL estimation performed monthly for the first 6 months of the survey, bimonthly for 1 year and every 3 months from the second year onwards. Therapy was resumed at a loss of major molecular response (MMR, BCR-ABL ≥ 0.1 % IS).

Results. The MMR loss upon the TKI withdrawal was observed in 48 (49 %) patients. Survival without MMR loss was 52 % past 24 months since withdrawal, with a median of 35 months (23–52). The duration of therapy, MR and the MR depth at the time of withdrawal significantly correlated with a conserved post-therapy MMR. Gender, age, a Sokal risk group, type and line of TKI therapy at withdrawal, and imatinib resistance in history were not observed to significantly impact molecular relapse-free remission. MMR was recovered in all 48 patients with TKI therapy resumed in molecular relapse. In 65 % of the patients, adverse therapy events observed during treatment completely resolved by 6 months of post-therapy monitoring. Musculoskeletal pain (withdrawal syndrome, WS) was reported in 42 % patients in the post-therapeutic period, which did not lead to TKI resumption. The WS development correlated with an elder age and longer therapy prior to withdrawal.

Conclusion. Molecular relapse-free survival in CML patients with treatment-free remission (TFR) is comparable to other published evidence. Monitoring safety during TFR is attested by the lack of disease progression and MMR recovery upon TKI resumption in all patients.

Introduction. Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for chronic myeloid leukaemia (CML).

Aim. Analysis of allo-HSCT outcomes in CML patients following reduced-intensity conditioning (RIC) regimens.

Materials and methods. This retrospective study included 110 CML patients who underwent allo-HSCT in 1995–2019. RIC regimens included busulfan (8–12 mg/kg), fludarabine (180 mg/m²) or melphalan (140 mg/m²), fludarabine (180 mg/m²). The median onset time for treatment with tyrosine kinase inhibitors (TKIs) was 60 days after allo-HSCT (30–835). Post-transplant graft-versus-host-disease (GVHD) prevention with cyclophosphamide (Cy) at high doses (PTCy) of 50 mg/kg in 3–4 days after allo-HSCT (D+3, D+4) was ordered in 61 % (n = 67), with antithymocyte globulin (ATGAM) 60 mg/kg — in 17 % (n = 19), with thymoglobulin 5 mg/kg — in 3 % (n = 3) of the patients.

Results. In the study cohort, 50 % (n = 55) of the patients had chronic phase 2 and higher (CP ≥ 2), 25 % (n = 27) — accelerated phase (AP), 9 % (n = 10) — blast crisis (BC) phase of the disease. Among CP ≥ 2 patients, 63 % (n = 58) had a BC in history, and 25 % (n = 23) — 2 or more BCs. One-year non-relapse mortality (NRM) was 21 % (95 % CI 15–31). PTCy prevention of GVHD significantly reduced the NRM risk relative to other schemes: 11 % (95 % CI 5–20) vs. 38 % (95 % CI 23–53) (p = 0.001). Acute GVHD II–IV had a rate of 23 % (95 % CI 15–31), chronic GVHD of moderate to severe degree 15 % (95 % CI 9–22). TKIs were used in 49 % (n = 29) cases for relapse prevention, in 40 % (n = 24) — due to the lack of response to allo-HSCT, in 10 % (n = 6) — in relapse. Donor lymphocyte infusion (DLI) was performed in 37 patients mainly in BCR-ABL positive cases (24 %, n = 9) and relapse (49 %, n = 18). Three-year relapse rate was 36 % (95 % CI 26–46), and five-year relapse-free survival (RFS) was 40 % (95 % CI 29–51). Transplantation in AP or BC phase significantly increased the relapse rate (odds ratio 2.4800 (1.2180–5.050), p = 0.012). Five-year overall survival was 52 % (95 % CI 40–62), a clean BC history and PTCy correlated with a higher 5-year overall survival (odds ratios 1.9990 (1.0700–3.7350), p = 0.029, and 0.3126 (0.1670–0.5851), p = 0.0002, respectively).

Conclusion. Reduced-intensity conditioning is advantageous in patients with long-term CML and several lines of TKI therapy in history. Post-transplant complication relief is associated with PTCy prevention. Relapse instances, however, complicate the outcomes of allo-HSCT with RIC. Post-transplant TKI and DLI facilitate response in 54 % of the patients. Success of allo-HSCT largely depends on the disease phase (CP, AP, BC) at the time of transplantation.

Background. In the superior vena cava syndrome, vein catheterisation provides an alternative for vascular access. Few reports describe the usage of femoral ports.

Aim. Description of pros and contras for femoral port installation in patients with haematological malignancies and the superior vena cava syndrome.

Materials and methods. This prospective non-randomised, single-centre study included 163 haematological patients implanted 72 ports in superior vena cava, 35 — in inferior vena cava and inserted with 156 non-tunnelled femoral catheters. Catheterisation properties, complications, duration of use and reasons for port and catheter removal were registered.

Results. No significant differences were observed between ports in superior and inferior vena cava as per the frequency of urokinase use in catheter dysfunction, catheter dislocation, catheter-associated bloodstream and pocket infections. Differences were revealed in the catheter-associated thrombosis rate, which was higher with femoral access (17.0 % or 0.9/1000 catheter days vs. 8.3 % or 0.2/1000 catheter days, p = 0.017). Ports in inferior vena cava had a lesser duration of use than in superior vena cava (p = 0.0001). Unlike femoral ports, non-tunnelled femoral catheters had higher rates of catheter-associated thrombosis (9/1000 vs. 0.9/1000 catheter days, p = 0.002) and infection (4.9/1000 vs. 0.3/1000 catheter days, p = 0.002). One lymphoma therapy course required one femoral port or 1 to 14 (median 3) non-tunnelled femoral catheters.

Conclusion. Femoral port implantation is a necessary measure in patients with the superior vena cava syndrome. It has advantages in terms of catheterisation frequency, lower infectious and thrombotic complication rates compared to non-tunnelled femoral catheters.

Introduction. The main pathogenetic mechanism of the development of aplastic anemia (AA) is a violation of the immune regulation of hematopoiesis.

Aim: to study of the subpopulation composition of T-cells and the repertoire of the T-cell receptor in AA patients.

Patients and Methods. The study included AA patients (n = 40) without prior immunosuppressive therapy in 2018–2020. The T-cell subpopulation structure and T-cell receptor Vβ-family (TCR-Vβ) oligoclonality were studied in samples of bone marrow using flow cytometry.

Results. We report characteristic properties of T-cell subpopulations of bone marrow in all AA patients: elevated counts of cytotoxic T-cells, effector CD4⁺ and CD8⁺ cells, CD4⁺ memory cells, which may suggest a long-term antigenic stimulation with subsequent activation of these cell subpopulations resulting in hyperexpression of pro-inflammatory cytokines. Diminishing of naive CD4⁺ and CD8⁺ cells, regulatory and double negative T-cells may indicate a relaxing control of cytokine-producing T-cells. A relationship has been established between the AA severity and counts of effector, regulatory, double negative and PD-1 positive T-cells. A highest count of potentially cytokine-producing T-cells and lowest count of cells involved in T-cell activity regulation were observed in very severe AA patients. Studies of the TCR-Vβ repertoire revealed oligoclonal expansion in the cytotoxic T-cell subpopulation.

Conclusion. Enrichment in selected Vβ families suggests autoreactive T-cell clonality and attests to the immune nature of AA. A dynamic TCR-Vβ repertoire assay may be recommended in the disease monitoring. Flow cytometry helps identify valuable biomarkers for T-cell clone monitoring in AA and a better assessment of the disease progression.

Introduction. Whole-body diffusion-weighted magnetic resonance imaging (MRI) is an informative method for bone marrow infiltration diagnosis in patients with multiple myeloma (MM) and post-monitoring in autologous haematopoietic stem cell transplantation (auto-HSCT).

Aim: to study bone marrow lesions in MM patients using whole-body MRI prior to and after chemotherapy with subsequent auto-HSCT.

Materials and methods. Forty patients with MM were included in a prospective study of whole-body MRI before and after high-dose chemotherapy with auto-HSCT. All patients had whole-body MRI prior to and at +100 day of auto-HSCT. Antitumour response was assessed after induction and at +100 day. The number and volume of bone marrow lesions prior to and at +100 day of auto-HSCT were determined, along with apparent diffusion coefficient (ADC) in the lesions.

Results. We observed a significant reduction of 29 % in the number of lesions, 40 % — in their volume and 33 % — in ADC. A significant correlation was revealed between relative reduction in the number and volume of foci (r = 0.52, p = 0.0017). A correlation was found between relative reduction in the foci number and ADC (r = 0.47, p = 0.016). Patients with lesions > 7 cm³ in MRI data exhibited a lesser reduction in the foci number and volume and ADC values after auto-HSCT compared to patients with lesions < 7 cm³.

Conclusion. Whole-body MRI with diffusion-weighted imaging and subsequent estimation of the number and volume of lesions and their ADC values prior to and after auto-HSCT add power to assessing antitumour response in MM patients with auto-HSCT.

Introduction. Acute myeloid leukaemia (AML) is associated with multiple driver mutations, which prognostic value remains understudied.

Aim. Assessment of the frequency of mutations in various genes and their impact on acute myeloid leukaemia outcome in adults.

Materials and methods. The study included 90 adult patients with newly diagnosed AML; 76 were aged under 60, 14 were 60 and more years old. Patients under 60 had chemotherapy (CT) “7+3” as induction, the elder cohort had variant low-dose CT with hypomethylating agents. The molecular genetic status of patients was determined using next-generation sequencing; the in-house gene panel included ASXL1, BCOR, DNMT3, FLT3, IDH1, IDH2, PIGA, RUNX1, SETBP1, SF3B1, SRSF2, TET2, TP53 and U2AF2.

Results. Nucleotide substitutions were identified in genes DNMT3, TET2, TP53, SETBP1, BCOR, RUNX1, IDH2, IDH1, FLT3, U2AF2, SF3B1 in 57.8 % of the patients (n = 52), with 17.8 % (n = 16) having compound mutations in two or three genes. Treatment efficacy and long-term outcomes were assessed against age, ELN-2017 risk groups and mutations in genes TP53, RUNX1, IDH1, IDH2 and DNMT3. In the long term, a reliable variation was revealed in the overall survival (OS) rate with respect to mutations in genes TP53 and RUNX1. Patients with mutant TP53 had 30 % OS, those with the intact gene — 53.4 % (p = 0.0037). Similar results were obtained with RUNX1: mutations marked 20 % OS, intact patients had 54% OS (p = 0.0466).

Conclusion. Mutations in genes FLT3-ITD, NPM1 and CEBPA are proxy to AML. However, a more accurate prognosis and optimal choice of therapy require detailed molecular profiling due to genetic heterogeneity of AML patients.

Introduction. Measurable residual disease (MRD) is a residual amount of malignant cells able to invoke relapse after complete haematological remission.

Aim. Analysis of the MRD prognostic value in various treatment protocols for acute leukaemia.

Main findings. MRD is a good prognostic indicator in lymphoblastic and myeloid leukaemia. Quantification of residual tumour cells is used for patient risk stratification according to the relapse prognosis. Stratification data, including MRD estimates at check points, may impact therapy choice, such as transplantation of allogeneic haematopoietic stem cells. Therefore, MRD estimation in acute leukaemia has become mandatory in clinical trial and research.

Introduction. Thrombosis and thromboembolism are frequent complications in chronic glomerulonephritis (CGN) with nephrotic syndrome (NS), despite the use of anticoagulant therapy. Therefore, the questions of thrombosis risk assessment and thrombotic complication prevention in NS are still relevant.

Aim. Description of the frequency and localisation of thromboembolic complications in CGN-NS patients and a review of approaches to their risk assessment and prevention.

Main findings. The main risk predictors of venous thrombosis in NS are considered, including low serum albumin, high plasma D-dimer, age over 60 and hypovolemic conditions. The risk of arterial thrombosis is determined by general population factors: age, gender, smoking, diabetes mellitus and arterial hypertension. Venous thrombosis may be asymptomatic and mainly occurs in deep lower limb veins, renal veins and branches of pulmonary artery. Among the NS-associated CGN morphotypes of high risk are membranous nephropathy and membranoproliferative CGN. Issues in the thrombotic complication risk assessment, prevention and treatment are highlighted.

Introduction. Mutations in the TP53 gene in patients with mantle cell lymphoma (MCL TP53+) are associated with a low response to intensive chemotherapy (CT) and adverse outcomes. Allogeneic haematopoietic stem cells transplantation (allo-HSCT) is a curative approach in MCL-TP53+ patients.

Aim. Efficacy and safety assessment of allo-HSCT in MCL-TP53+ patients.

Main findings. During 2016–2020, allo-HSCT in MCL TP53+ was performed in three patients. Two of them were grafted from HLA-identical unrelated donors, and one — from a haploidentical donor. Pre-transplant conditioning was “fludarabine + treosulfan + melphalan” in one case, and “fludarabine + busulfan” — in the other two. In three patients, leukocyte and platelet counts were recovered at days +18 and +20, +17 and +21, +19 and +16 after allo-HSCT, respectively. Acute graft-versushost disease (aGVHD) was observed in all patients (grade I — in 2 patients, grade IV — in 1 patient). One patient developed chronic GVHD (cGVHD) of moderate grade. All three patients exhibited complete remission and 100% donor chimerism in allo-HSCT follow-up of 6, 15 and 40 months, respectively.

Intoduction. Multiple myeloma (MM) and chronic myelogenous leukaemia (CML) are two haematological malignancies developing through tumour transformation of lymphoid and myeloid progenitor cells, respectively, not sharing a common ancestry. Coexistence of the two diseases is extremely rare.

Aim. Clinical description of a patient diagnosed with CML in a few months after start of MM therapy.

Main findings. We report a clinical case of MM and CML in a 62 years-old female patient. MM was diagnosed newly and followed by 5 VD chemotherapy cycles. Treatment discontinued due to severe polyneuropathy. The patient was transferred to thalidomide maintenance therapy. CML was diagnosed 12 months after initiation of thalidomide therapy: BCR-ABL (p190), BCR-ABL (p210). Since imatinib produced short-term effect, dasatinib therapy was started. Following 16 months after the onset of dasatinib therapy, MM relapse and CML progression were diagnosed.

Introduction. Anaemia is a complication of primary hyperparathyroidism (PHPT). Pathogenesis of PHPT-induced anaemia involves inhibited erythroid cell proliferation associated with the underlying disease and non-specific factors (blood loss, chronic kidney disease). However, its specific mechanisms remain unclear.

Aim. Clinical description of a PHPT case with multifactorial complicating anaemia.

Main findings. With putative evidence existing on relationships between PHPT and anaemia, no large clinical trials substantiated suitable algorithms for such patients’ management. The genesis of anaemia reported in this case was multifactorial and not decisively excluding PHPT from putative causes.