Preview

Oncohematology

Advanced search
Vol 13, No 2 (2018)
View or download the full issue PDF (Russian)
https://doi.org/10.17650/1818-8346-2018-13-2

HEMATOLOGIC MALIGNANCIES: DIAGNOSIS, TREATMENT, SUPPORTIVE CARE

9-20 9847
Abstract

Objective. To define the epidemiology of venous thrombosis (VT) in children, adolescents and young adults with lymphomas, to identify the thrombotic risk factors and VT’s prognostic value.

Materials and methods. We reviewed the medical records of 513 lymphoma patients (284 with Hodgkin's lymphoma (HL) and 229 with non-Hodgkin lymphoma (NHL)) aged from 0,6 to 26 years (median – 14 years), diagnosed with lymphomas in 2005–2017. Risk thrombotic factors were assessed using binary Cox regression in univariate and multivariate models with calculation of the odds ratio (OR) with 95 % CIs.

 Results. Twenty-eight of 513 patients (5.5 %, 95 % CI, 4.5–6.5 %) were diagnosed as having VT with a total of 32 thrombotic events. The incidence of VT in NHL patients (23/229, 10.5 %, 95 % CI, 8.5–12.5 %) was higher than in HL patients (5/284, 1.8 %, 95 % CI, 1.0–2.6 %, p <0.0001). VT was associated with venous catheterization (VC) in 53.6 % and with local compressive effect in 32.1 % cases. VT occurred during the first 6 weeks after lymphoma diagnosis in 57.1 % patients. Genetic predisposition to thrombosis (FV Leiden и FII G20210A mutations) was revealed in 3 (10.7 %) patients. The recurrence rate of VT was 14.3 %. Age older than 13 years (ОR 2.5, 95 % CI, 1.1–6.0, p <0.05) and lymphoblastic lymphoma (LL) subtype (ОR 5.5, 95 % CI; 2.3–13.6, p <0.01) independently associated with the occurrence of VT in NHL patients. In HL group all cases of VT were detected in patients older than 15 years. The only risk factor predisposing patients with HL to VT was significant mediastinal lymphadenopathy (bulky disease) (ОR 7.0, 95 %; 1.2–42.3, p<0.05). The presence of VT did not influence OS of NHL patients (73.7 %, SE 9.2 % (n = 23) versus 83.4 %, SE 9.2 % (n = 206), p >0.05), but had a negative impact on the OS of HL patients (60.0 %, SE 21.9 % (n = 5) versus 94.8 %, SE 1.5 % (n = 279), p <0.001). HL patients older than 15 years with bulky disease (38/284, 13.4 %), had a high thrombotic risk with lower OS of 78.8 ± 8.3 %, p <0.001.

Conclusion. Cumulative incidence of VT in NHL patients was higher than in HL patients. Age older than 13 years and LL were independent thrombotic risk factors for NHL patients. Age older than 15 years and bulky disease increased risk of VT in HL patients. VT occurrence decreased OS of young HL patients. It may be necessary to delay the central VC of vena cava superior in children with massive mediastinal tumor. Prophylactic anticoagulation for high thrombotic risk patients might be warranted.

21-31 9851
Abstract

Despite the development and active use of modern high-effective therapeutic protocols for pediatric non-Hodgkin’s lymphomas (NHL), treatment results of relapses and refractory disease are unsatisfactory. In the current issue international practices and own experience in relapsed/refractory pediatric NHL are presented: lymphoblastic lymphomas, anaplastic large cell lymphoma, and heterogeneous group of mature B-cell lymphomas. Chemotherapy protocols, results of nelarabine, rituximab, crizotinib, brentuximab vedotin, stem cell transplantation use for relapsed/refractory pediatric NHL treatment are presented. In 27 relapsed NHL patients treated inN.N.BlokhinNationalMedicalResearchCenterof Oncology, overall survival was 29.1 ± 7.9% (median follow-up 56.3 ± 14.4 months). Primary refractory NHL cases were fatal. Own and literature data make it necessary further study of new therapeutic approaches aimed at improvement of results in relapsed/refractory NHL.

32-38 10105
Abstract

In recent years, great progress has been made in understanding biology and pathogenesis of chronic lymphocytic leukemia. The key thing in disease pathogenesis is the apoptosis resistance of tumor cells. One of the main regulators of programmed cell death is the Bcl-2 family proteins. Important role of Bcl-2 protein in carcinogenesis made it an attractive target for therapeutic intervention. This review focuses on venetoclax (a selective inhibitor of the anti-apoptotic Bcl-2 protein) in the treatment of chronic lymphocytic leukemia.

39-47 9965
Abstract

In the retrospective multicenter study during 2007–2017 we included 59 oncohematological patients with mucormycosis and 541 patients with invasive aspergillosis. Our study showed that mucomorhycosis more often developed in children and adolescents (p = 0.001), and after «graft versus host» disease development (p = 0.0001). Patients with mucormycosis were more immunosuppressed: severe neutropenia was in 88 % vs. 82 %, median duration of neutropenia ‒ 30 days vs. 14 days, p = 0.0001, lymphocytopenia – 77 % vs. 65 %, median duration of lymphocytopenia – 25 days vs. 14 days, p = 0.001. The main sites of infection were lungs, nevertheless in patients with mucormycosis it was less frequent (73 % vs. 97 %, p = 0.02), but more frequent were ≥2 organs involvement (42 % vs. 8 %, p = 0.001) and paranasal sinuses involvement (15 % vs. 6 %, p = 0.04). Typical clinical features of mucomorhycosis were localized pain syndrome (53 % vs. 5 %, p = 0.0001), hemoptysis (32 % vs. 6 %, p = 0.001), on lung computed tomography scan – pleural effusion (53 % vs. 7 %, p = 0.003), lesions with destruction (38 % vs. 8 %, p = 0.0001) and “a reverse halo” symptom (17 % vs. 3 %). The overall 12-week survival was significantly lower in patients with mucormycosis (49 % vs. 81 %, p = 0.0001). In both groups unfavorable prognosis factors were: ≥2 organs involvement (p = 0.0009) and concomitant bacterial or viral infection (p = 0.001 and p = 0.008 respectively). In mucormycosis patients favorable prognosis factor was remission of underlying disease (p = 0.006), in invasive aspergillosis patients – early bronchoscopy (p = 0.003), voriconazole use (p = 0.0007) and secondary antifungal prophylaxis (p = 0.0001).

48-61 10373
Abstract

Modern anticancer therapy due to its intensity and molecular biology orientation allows achieving higher efficiency and theoretically reducing the incidence of complications. However, the increase in efficacy in the modern oncology really exists, but reducing complication frequency, unfortunately, is far from being solved. In many respects the problems of diagnosis, treatment and complications monitoring are associated with the impact on the complex physiological processes occurring in oncological patient. Timely implementation of modern and adequate programs for the prevention and treatment of these complications defines the concept of “supportive therapy”, which provides at least half the effectiveness of antitumor treatment.

To date, according to most studies, the most frequent complications of antitumor therapy are hematologic, in particular – anemia. In clinical practice, blood transfusions, recombinant human erythropoietins, hemopoiesis stimulating cofactors are used to correct this type of complications. The need for anemia treatment is determined by its negative impact on quality of life, as well as a negative prognostic impact on the life expectancy of cancer patients, because hypoxia of tumor tissue can be associated with resistance to chemoand radiation therapy, the stimulation of genetic mutations and neoangiogenesis, which make it difficult to control of tumor growth. In numerous studies using multivariate analysis confirmed the association of low hemoglobin levels and/or tumor tissue hypoxia with worsening prognosis and overall survival in many types of tumors. The modern anemia treatment should not be determined only by increased in hemoglobin level, but should be considered as an active prophylaxis for its reducing. Recombinant forms of human erythropoietin and intravenous forms of iron preparations should be the most popular correction methods in everyday practice.

The high cost of complex anemia therapy and the social significance of oncological diseases necessitate a pharmaco-economic analysis of registered in Russia erythropoietin preparations and the optimization of existing anemia treatment regimens in cancer patients in order to reduce the expenditures of the health budget. At present, an active import substitution program is underway in the Russian Federation to support the development of the Russian pharmaceutical industry and provide the population with more affordable medicines while maintaining its quality and efficiency. The need to address these issues, and the effective use of the domestic biological analogue epoetin alfa, served as an excuse for performing a comparative clinical and economic analysis. They were selected drugs that differ in pharmacokinetic properties: Eralfon® – analogue of epoetin alfa and Aranesp® – darbepoetin alfa.

The treatment model of adults oncological patients with anemia receiving chemotherapy was created, which takes into account various therapies using erythropoietin preparations. The total therapy cost for an oncological patient with anemia is less when using short-acting erythropoietin – epoetin alfa – 131 609 rubles in comparison with the long-acting erythropoietin – darbepoetin alfa – 245 159.2 rubles, the difference was 113 550.2 rubles (–46 %) in favor of the epoetin alfa.

According to pharmaco-economic analysis, the treatment of anemia with a Russian-produced drug epoetin alfa (Eralfon®) is preferred in comparison to darbepoetin alfa (Aranesp) in adult cancer patients with nonmyeloid malignancies in the Russian Federation, as it allows increasing the number of treated patients at a cost reduction.

62-72 10550
Abstract

Refractoriness to transfusions of platelet concentrates (PC) adversely affects the conduct of complex therapy in hematological patients. Individual selection of platelets is recommended for such patients. In cases of high degree of alloimmunization with the formation of polyspecific antibodies, when individual selection is difficult, procedures plasmapheresis (PPs) is included in the treatment program.

Aims: to evaluate the effectiveness of PC transfusions by individual selection in patients refractory to transfusions and the use of PPs as a second line therapy in combination with individual platelet selection.

Materials and methods: from September 2015 to December 2017, 91 patients with refractory to PC transfusions from 1263 patients who received PC transfusion were observed in the center’s clinics. The median age was 43 (18–71) years. M/F – 38/53. Patients: 20 – aplastic anemia (AA), 17 – myelodysplastic syndrome (MDS), 45 – acute myeloid leukemia (AML), 9 – acute lymphoblastic leukemia (ALL). All patients underwent PC transfusion by individual selection (HLA/HPA) Immucor’s Capture-P solid phase technology. In 28 (30 %) of 91 patients, due to the inability to select, there was a need for PP as a second line therapy. Patients: AA – 4 (20 %); MDS – 8 (47 %); AML – 12 (26 %); ALL– 4 (44 %). The median age was 48 (23–71) years. M/F – 8/20. From 2 to 15 procedures were performed (on average – 6) for each patient. All patients received PC transfusions by individual selection by cross-matching immediately after the PP procedure. The efficacy of PC transfusions was assessed by Absolute Platelet Increment (API) and Corrected Count Increment (CCI), relief of hemorrhagic syndrome.

Results: in 26 of 28 refractory to PC transfusions patients, in the absence of compatible donor platelets, carrying out PPs in combination with subsequent individual platelet selection promoted relief of hemorrhagic syndrome, increase in API from 3.3 × 109/L at 29.5 × 109/L and CCI from 1.3 to 10.7. Against the background of PPs, combined with individual selection, the degree of alloimmunization (the percentage of incompatible pairs) decreased on average: AA (n = 4) – from 91.7 to 50.2 %; MDS (n = 8) – from 89.6 to 31.6 %; AML (n = 12) – 86.0 to 40.5 % and ALL (n = 4) – from 91.7 to 37.7 %. In 2 patients with a high degree of alloimmunization and after carrying out PPs, it was not possible to select compatible platelets, PC transfusions were ineffective (API = 5 × 109/L, CCI = 1), and hemorrhagic syndrome was not completely managed, but its severity was reduced.

Conclusions. With the development of refractoriness to PC transfusions and the ineffectiveness of individual platelet selection, PPs should be used as the second line of therapy, which, combined with individual selection, increases the likelihood of compatible donor-recipient pairs and increases the clinical efficacy of PC transfusions. When PPs is ineffective in combination with individual selection, it is necessary to exclude the syndrome of increased consumption and other mechanisms of refractoriness.

73-81 10542
Abstract

Objective. To study the histological structure of bone marrow (BM) and plasmacytoma tumor substrate in patients with multiple myeloma (MM). Materials and methods. The study included 35 patients (19 men and 16 women) aged 23 to 73 years with newly diagnosed MM. At the first onset of the disease plasmacytoma was diagnosed in 21 patients: bone plasmacytoma, associated with skeletal bones – in 14 patients; extramedullary plasmacytoma, emerging in various organs not connected with bone tissue – in 7 patients. All patients underwent BM trephine biopsy and plasmacytoma biopsy with subsequent histological examination. BM and plasmacytoma histological specimens were studied using LEICA DM4000B microscope. Frequency domain analysis (cross tables, Fisher–Freeman test) was used for data statistical analysis.

Results. The analysis showed that the histological features of BM in MM patients with extramedullary plasmacytoma statistically significantly differed from that in MM patients with bone plasmacytoma and without plasmacytoma. As a result of the analysis, the relationship between BM morphological variant and tumor advancement became apparent. When comparing the morphological pattern of the bone and extramedullary plasmacytomas, no significant differences were found, however, the substrate of the extramedullary plasmacytoma was more often represented by tumor cells with immature morphology as compared to the substrate of the bone plasmacytoma.

Conclusion. The established differences in the histological structure of the BM in MM patients with extramedullary plasmacytoma suggest that this type of the disease stands apart and requires further detailed pathomorphological study.

HEMATOPOIETIC STEM CELL TRANSPLANTATION

82-92 10139
Abstract

Allogeneic stem cell transplantation (alloHSCT) is effective curative option for a broad range of primary immunodeficiencies (PIDs). Hematopoietic chimerism monitoring in patients with various PIDs and its connection with the outcome of alloHSCT is of great interest. In this study 16 alloHSCT in patients with PIDs were included. Three-year overall survival was 72.2 ± 12.0 %. Full donor chimerism (FDC) was achieved in 13 (81.25 %) patients. Prolonged persistence of mixed chimerism (MC) was observed in 3 (18.75 %) patients. In patients with MC in the peripheral blood, circulating T-cells are completely or predominantly of donor origin, whereas granulocytes are predominantly or completely recipient cells, and chimerism in B-cells differs significantly from 0 % chimerism to FDC. In patients with PIDs, engraftment of individual cell lines (split chimerism) could be observed. In some patients chimerism decreased during the first year after alloHSCT with its subsequent stabilization. Increasing MC is not associated with transplant rejection in PIDs. FDC in patients with PIDs provides restoration of all cell lines participating in the immune response regardless of the diagnosis, but it is associated with more frequent development of «graft-versus-host» disease (GVHD), which is a serious complication of alloHSCT and can lead to treatment-related mortality (TRM). MC/split chimerism, in which the frequency of development of GVHD is less, can also provide the formation of a full immune response and correction of other disease manifestations, but only when replacing defective cell lines according to the diagnosis.

BASIC RESEARCH

93-99 9698
Abstract

Russian Scientific Research Institute of Hematology and Transfusiology under the Federal Medico-Biological Agency; 16 Vtoraya Sovetskaya St., 191024 Saint Petersburg, Russia

Polymorphism of platelet glycoproteins GPIIIa (T1565C), GPIba (T434C), GPIIb (T2622G) and GPIa (A1648G) genes, responsible for the formation of alloantigenic platelet systems HPA-1, -2, -3 and -5, in patients with chronic immune thrombocytopenia (ITP) and in control group (CG) was investigated. Among ITP patients, the proportion of homozygotes of the GPIIb 2622 GG (HPA-3b/3b) gene was more than 2 times higher than in CG: 23.9 % versus 11.4 % (odds ratio (OR) = 2.4, 95 % confidence interval (CI): 1.0–5.8, p = 0.05). The frequency of HPA-3a/3a (GPIIb 2622TT,843Ile/Ile) genotype was higher in ITP patients with 2–3rd degrees of hemorrhagic syndrome (HS): 55.6% versus 25.0% in the group with 0–1st degree of HS (OR = 3.8, 95 % CI: 1.3–10.7, p = 0.02). The obtained data suggest the effect of T2622G polymorphism GPIIb gene both on development of disease (2622 GG genotype), and on serious manifestations of HS (2622 TT genotype), which allows considering this polymorphism as unfavorable prognostic criterion in ITP patients.

RARE DISEASES

100-104 10117
Abstract

Storage diseases (thesaurismosis, storage reticuloses) are the complex and extensive group of diseases in which differential diagnosis of pathological changes from the internal organs is difficult. For diagnosis and dynamic observation of liver and spleen lesions, ultrasound and X-ray computed tomography are used among imaging techniques. Among the imaging techniques for diffuse liver diseases, ultrasonography and X-ray computed tomography are most commonly used for their diagnosis and follow-up. Magnetic resonance imaging (MRI) has the highest sensitivity and specificity in diagnosing liver diseases.

The article considers the current MRI procedures that are used to diagnose storage diseases and to quantify found changes. For Gaucher disease, the potentials of such novel technique as magnetic resonance spectroscopy are described. Incorporation of MRI into the examination algorithm for patients with storage diseases will be able to improve the detection of these rare diseases and to monitor the efficiency of performed therapy.

PRESS RELEASE



Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1818-8346 (Print)
ISSN 2413-4023 (Online)