HEMATOLOGIC MALIGNANCIES: DIAGNOSIS, TREATMENT, SUPPORTIVE CARE
From 2001 to 2013 eleven patients with relapsed acute promyelocytic leukemia (APL) (median age – 30 years) received arsenicum trioxide (ATO). ATO was administered as a 2nd line relapse therapy in 9 patients, as 1st line relapse therapy in 2 patients. ATO was administered in a dose of 0.1 mg/kg in 7 patients, 0.15 mg/kg – in 4 patients. The induction duration was 14 days in 3 patients, 24–35 days in 2 patients, 60 days in 6 patients. From the 1st day of ATO patients received 45 mg/m2 all trans retinoic acid (ATRA) (1 patient – from day 29 of ATO therapy). Maintenance therapy ATO + ATRA (10–14 days courses, every four weeks) patients were receiving during 10–15 months. 2 from 3 patients with molecular relapses achieved remission lasting 57 and 89 months after the 14-day ATO courses. 1 from 2 patients with bone marrow relapse achieved remission lasting 27 months after the 24–35-day ATO courses. 60-day courses were effective in 5 of 6 patients: in 4 of which remission are retained during 16, 19, 27, 57 months; 1 patient was relapsed after 12 months; 1 patient did not achieve molecular remission. 3 patients received allogeneic hematopoietic stem cell transplantation (alloHSCT), 2 of which alive in remission. 1 patient received autologous hematopoietic stem cell transplantation in the 2nd molecular remission (alive in remission). 4 patients died: 1 – in the 3rd relapse (duration of 2nd remission – 9 months), 1 – in remission from complications after alloHSCT, 1 – from APL progression, 1 – sudden death in 2nd remission lasting 72 months. ATO + ATRA for 60 days with supportive therapy are more effective than chemotherapy in the treatment of APL relapse. Interferon α + ATRA are inappropriate treatment of APL molecular and cytogenetic relapse. Using autologous HSCT in 2nd molecular remission will improve the results of APL relapse treatment.
Introduction. Based on clinical studies data voriconazole is recommended as the drug of choice for treatment of invasive aspergillosis (IA) – a widespread infectious complications occurring in immunocompromised patients and is characterized by severe clinical course and high mortality.
The aim of this study was to assess the cost-effectiveness of voriconazole compared to other preparations recommended in the Russian practice for the treatment of IA in adult patients.
Materials and methods. The authors constructed a «decision tree» type of model, which compared the three treatment alternatives for the IA in adult patients, depending on the drug in first-line therapy: 1) voriconazole, 2), caspofungin, or 3) amphotericin B lipid complex (LC). Efficacy was assessed as the probability of patient survival within 14 weeks of starting treatment. We took into account the drugs cost and an increase in the hospitalization duration due to the development of serious adverse events. The model parameters were determined on the basis of the published results of clinical studies, the costs were calculated on the basis of medicines prices in the public procurement and the average bed-day cost in system of obligatory health insurance. Probabilistic sensitivity analysis was performed.
Results. It has been shown that the use of voriconazole for treatment of IA is the dominant strategy compared to the use of caspofungin and amphotericin B LC, providing cost reduction while achieving maximum effect. Probabilistic sensitivity analysis (1000 simulations) showed stability of the revealed pattern.
Conclusion. The use of voriconazole in the treatment of IA allows to save the greatest number of lives at minimal cost compared to other preparations recommended in the Russian practice.
The newest advances in primary myelofibrosis (PMF) pathogenesis study, diagnostic and treatment approaches are presented in this article. The JAK-STAT signal pathway activation now recognized as main pathogenesis mechanism of PMF, it caused by JAK2, CALR, MPL genes mutations. Authors demonstrate their own data about epidemiology, clinical signs, diagnostic and treatment results of 315 PMF patients. The most frequent clinical symptoms are: anemia, leukocytosis, thrombocytosis, splenomegaly, constitutional symptoms. Diagnostic criteria, prognostic scales (including cytogenetic and molecular features) issues are reviewed. Intermediate-1 risk grade is in the most proportion of patients. The
recommended PMF treatment algorithm is listed. The treatment methods, target drugs (Janus kinases inhibitors) trials results are discussed.
Neutropenia and associated infection, resulting in hospitalization and use of antibiotics, has a negative effect on chemotherapy. The need to reduce the dose of cytotoxic drugs during neutropenia leads to lower survival rates in patients with hematological malignancies and solid tumors. Since 1990s myelocytokines – proteins that accelerate neutrophil recovery after cytostatic chemotherapy and reduce the risk of infection – is widely used in the clinical practice. The use of these drugs can support the planned dose intensity of chemotherapy and improves the treatment efficacy. The disadvantages of these drugs include the need for their daily parenteral administration for 7–10 days. The development of long-acting forms (pegfilgrastim and lipegfilgrastim) has solved this problem. Self-regulating clearance of prolonged forms allowed to use them only once on a chemotherapy course. Results of pegfilgrastim administration in 25 patients with hematological malignancies (8 patients) and solid tumors (17 patients) included in our analysis. Prolonged preparation showed high efficacy in secondary prophylaxis of neutropenia and infection decreasing the risk by 82 %. The single administration of pegfilgrastim allowed safe dose intensity chemotherapy with shorter intervals between courses (AC-14) in 8 patients with breast cancer. Tolerability was good; cases of hyperleukocytosis have notbeen reported. Recently in Europe and the Russian Federation a new drug from prolonged myelocytokine group – lipegfilgrastim – has been
registered. The results of two controlled trials in patients with breast cancer (n = 410) receiving doxorubicin/docetaxel showed high efficacy of the drug as the pegfilgrastim with comparable tolerability.
The paper presents the laboratory values by which modern differential diagnosis of anemias can be performed. This takes into account a wide
range of laboratory tests, including: serum ferritin, erythrocyte ferritin, serum iron, total serum iron binding capacity, iron transferrin saturation,transferrin, transferrin receptor, serum vitamin B12, erythrocyte vitamin B12, serum folate, erythrocyte folate, hepsidin, HIF-1 (hypoxiainducible factor-1), immunoglobulins on erythrocytes end others. The combination of these studies helps to accurate diagnosis and appropriate therapy.
BASIC RESEARCH
The goal was a comprehensive study of oral microflora in healthy children and those with hematologic malignancies, based on the analysis of mixed microbial biofilms composition, isolation and identification of new previously unknown microorganisms. The material was obtained in children with hematological diseases in remission, 2–10 years aged, and for the control group from St. Petersburg schoolchildren and in kindergartens. We used microbiological, biochemical and molecular genetic methods, including electron microscopy, proteomic analysis, sequencing and complete genome annotation. Microorganisms of 23 genera isolated as pure cultures and identified by biochemical activity from mixed microbial biofilm derived from saliva of healthy and sick children. In microflora of children with hematologic malignancies a previously unknown type of streptococci with a large number of antibiotic resistance genes was revealed. Differences in oral microbiota composition of healthy children and children with hematological diseases in remission were revealed. The microbiota of children with hematologic malignancies contains more genes controlling antibiotic resistance. Also, it was observed previously unknown bacterium of the genus Streptococcus.
Total RNA isolated from peripheral blood lymphocytes of donor and patient with polycythemia, stimulates hematopoiesis in rats with toxic
aplastic anemia due to benzene administration. Total RNA of lymphocytes from polycythemia patient has a more pronounced effect on the erythroid, myeloid and megakaryocytic hematopoiesis comparing to total RNA from donor lymphocytes. The greatest stimulatory effect
of RNA observed after 21 days from the start of experiment. Total RNA of lymphocytes from polycythemia patient largely activates erythropoiesis promoting restoration of reticulocyte count in animals with aplastic anemia.
Platelet concentrates (PC) are used worldwide in the fields of oncology, oncohaematology and bone marrow transplantation. One of the main tasks of clinical transfusiology is the development and improvement of technologies aimed to increase quality and safety of PC. In particular, such technologies are represented by using of platelet additive solutions (PAS). The main advantages of this approach are: a reduction of immune and non-immune transfusion reactions risk, an improvement of pathogen inactivation quality and enhancing a clinical effect of PC transfusions after storage. Numerous different PAS and methodologies of their application are suggested to date. In this review we have described and classified recent data on different PAS and the benefits of their clinical application.
ISSN 2413-4023 (Online)