Certain Aspects of Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma

The review dwells on certain problems of mobilization and conditioning regimens, as well as autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma. The aim of the review is to determine new approaches to improve the effectiveness of the auto-HSCT

Correction of Anemia and Evaluation of Efficacy of Red Blood Cell Transfusion in Patients with Oncohematological Diseases

Aim. To study the quality of life (QL) of patients with oncohematological diseases and anemia with respect to hemoglobin level and to evaluate the efficacy of red blood cell transfusion (RBCT). Materials & Methods. QL of patients (n = 326) was studied using FACT-An questionnaire. RBCT efficacy was evaluated in two groups. The first group included patients (n = 28; 13 men and 15 women) with oncohematological diseases and chronic anemia aged 23–80 (median 65) years, the second (control) group included patients (n = 12; 11 men and 1 woman) after severe blood loss after injury (acute anemia) aged 25–43 (median 36) years. The baseline levels of hemoglobin (Hb) and hematocrit (Ht) were 80 g/L and > 25 %, respectively. Results. The association between the severity of anemia and QL was shown. The lowest QL was observed in patients with grade III–IV anemia (Hb 60 % only in 67.9 % of patients in the first group and in all the patients (100 %) in the second group. In 32.1 % of patients with various forms of hematologic cancer and chronic anemia tissue hypoxia was still observed after RBCT despite increased Hb > 80 g/L and Ht > 25 %. Therefore, it was proposed to raise the target Hb and Ht threshold levels for patients with low SvO2. Conclusion. The effect of the severity of anemia on QL was demonstrated. The patients with Hb < 80 g/L were shown to have low quality of life. SvO2 determination in anemia patients proved to be of great importance for RBCT efficacy evaluation. In patients with low SvO2 (< 60 %) RBCT should be continued until the target levels of Hb 100 g/L and Ht 33 % are reached

Hematopoietic Stem Cell Collection in Multiple Myeloma Patients: Influence of the Lenalidomide-Based Therapy and Mobilization Regimen Prior to Auto-HSCT

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 × 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 × 106/kg vs. 7.76 × 106/kg) tends to decrease CD34+ count (р = 0.066). Cyclophosphamide included into mobilization regimen compared to vinorelbine (3.96 × 106/kg vs. 6.8 × 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 lenalidomide treatment prior to auto-HSCT, intermediate-dose cyclophosphamide is preferred

Molecular Genetic Markers and Clinical Characteristics of Essential Thrombocythemia

Background & Aims. The presence of different molecular genetic markers of clonality (mutations in JAK2, MPL, CALR) or their absence (triple negative status, TN) in essential thrombocythemia (ET) indicates a biological heterogeneity of the disease and can determine its clinical forms. The aim was to evaluate the association of molecular genetic markers with the clinical form and the prognosis of ET. Materials & Methods. We analyzed the data of 240 patients with ET at the age of 20–91 years (median age 58.7 years), who were observed in the Russian Research Institute of Hematology and Transfusiology from 1999 to 2016 (median observation period 37.2 months). Results. The JAK2V617F (JAK2+) mutation was found in 182 (75.9 %) of 240 patients. CALR (CALR+) mutations were found in 30 (12.5 %): type 1 (CALR1+) mutations in 13/30 (43.3 %) and type 2 (CALR2+) in 17/30 (56.7 %). MPL (MPL+) mutations were found in only 2 (0.8 %) of 240 patients. None of the mutations were detected in 26 (10.8 %) of 240 patients (TN status). Significantly higher platelet counts were observed in CALR1+ and CALR2+ subgroups during the primary diagnosis of ET compared with JAK2+ and TN groups. The mean platelet counts were 1252 × 109/L for CALR2+ and 1079 × 109/L for CALR1+ vs 841 × 109/L (p < 0.001; p = 0.06) and 775 × 109/L (p < 0.001; p = 0.04) for JAK2+ and TN, respectively. Thrombosis was diagnosed in 50 (27.4 %) of 182 patients of the JAK2+ subgroup, in 8 (30.7 %) of the 26 patients of the TN subgroup, and in 2 (18.2 %) of 11 patients of the CALR1+ subgroup. No thrombosis was found in the CALR2+ and MPL+ subgroups (p < 0.001). In general, the CALR1+ status was characterized as the most favorable in terms of prognosis (5-year overall survival rate of 100 %), compared to the least favorable TN status (5-year overall survival rate of 85 %). Conclusion. Mutations in the CALR gene were characterized by a more favorable prognosis in comparison with JAK2+ and TN, as well as a decrease in the risk and frequency of thrombosis, despite higher platelet counts. TN-status of ET was associated with unfavorable prognosis

Correlation of CD34+ Hematopoietic Stem Cells and CFU in Peripheral Blood Apheresis Products in Patients with Malignant Lymphoproliferative Diseases Before and After Cryopreservation Prior to auto-HSCT

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

Genetic Markers of Hereditary Thrombophilia and Risk of Thrombotic Complications in Patients with Polycythemia Vera

Background. Thrombotic complications are one of the main problems of polycythemia vera (PV) treatment. They significantly impair the quality of life of these patients and may lead to the lethal outcome. A thrombotic event often precedes the diagnosis of this hematological disease. The pathogenesis of thrombosis in myeloproliferative neoplasms, PV, in particular, is a complex one. Prescription of antiaggregants in the absence of thrombosis and anticoagulants after a thrombotic event requires special attention and development of corresponding recommendations. The prescription of anticoagulants is impossible without taking into account the risks of hemorrhagic complications, which are also typical for myeloproliferative neoplasms. Aim. Assessment of the impact of hereditary thrombophilia genetic markers on the risk of thrombotic complications in patients with PV. Methods. The study examined 116 patients with PV, who were screened for markers of hereditary thrombophilia: factor V (G1691A, FV Leiden), prothrombin, methylenetetrahydrofolate reductase (MTHFR), fibrinogen (FI), plasminogen activator inhibitor (PAI-1), and platelet fibrinogen receptor type IIIA (GPIIIA). The incidence of these markers and their role in thrombosis in such patients was investigated. Results. The study provided data on the incidence of hereditary thrombophilia markers in patients with PV. Statistically significant differences in the incidence of these markers and homocysteine level were found between patients with thrombosis and without them. Conclusion. The information about the hereditary thrombophilia markers presence may be useful for the prescription of adequate antiaggregant and anticoagulant therapy for PV patients. Further research in this field is justified and it will probably demonstrate the relevance of hereditary thrombophilia markers as prognostic factors for thrombotic complications risk assessment

Role of Defects of Hematopoietic and Lymphoid Niches in Genesis of Chronic Lymphocytic Leukemia

Background & Aims. Niche-forming elements of the bone marrow and lymphoid organs play an important role in the pathogenesis of chronic lymphocytic leukemias. The aim is to determine multifunctional characteristics of stromal elements of the hematopoietic and lymphoid microenvironment involved in formation of a niche of hematopoietic stem cells and lymphoid precursor cells. Methods. Histological specimens of the bone marrow and lymph nodes of 112 CLL patients (64 men and 48 women) were investigated. 45 patients were included in the combined analysis group. The age median was 60 years. 50 volunteers were included in the control group: trepanobiopsy of the iliac area was performed in 30 healthy subjects, and lymph node biopsy was performed in 20 patients with reactive lymphadenopathy. Standard staining (hematoxylin-eosin, azure-II-eosin, silver impregnation, Masson stain) was used for histological studies. The immunohistochemical analysis was performed using the primary antibody panel and the polymer visualization system Dako according to staining protocol. Results. While analyzing 96 trepanobioptates, we isolated three types of bone marrow infiltration: nodular (18.8 %, n = 18), interstitial (27 %, n = 26) and diffuse (54.2 %, n = 52). Nodular and interstitial bone marrow infiltrations reflect a more favorable course of CLL as compared to the diffuse type. The morphological characteristics of the bone marrow stroma of CLL patients may be caused by both primary impairment of the hematopoietic microenvironment, and cytokine disbalance resulting from the effect on the stroma of the leukemic clone. The morphological examination of lymph node bioptate of CLL patients demonstrated impairment of histoarchitectonics of lymphoid tissue elements in all cases. In lymph nodes of CLL patients, we demonstrated the increased number of small vessels on the background of decreased expression of extracellular matrix protein expression: IV type collagen, laminin, and desmin. Disintegration of lymph node follicular dendritic cells network was demonstrated. Conclusion. Examination of the nature of the effect of stroma on hematopoiesis remains an urgent hematological problem. In order to solve the problem of regulatory influence, the use of morphological methods is recommended, including the immunohistochemical analysis