HEMATOLOGIC MALIGNANCIES: DIAGNOSIS, TREATMENT, SUPPORTIVE CARE
Use of tyrosine kinase inhibitor imatinib has led to significant progress in chronic myeloid leukemia (CML) treatment. To date, genetic monitoring is a mandatory attribute of therapy with tyrosine kinase inhibitors. The purpose of this study was to access the imatinib therapy efficacy in CML patients using complete molecular genetic monitoring by standard cytogenetics, realtime polymerase chain reaction and mutational analysis. Correlation between cytogenetic and molecular response was shown. Heterogeneity of molecular response in each patient group was revealed by expression of BCR-ABL. Kinase domain mutations were detected in 32 % of CML patients resistant to imatinib.
We performed clinical and laboratory characterization of patients with rare translocation t(1;11)(p32;q23) leading to MLL-EPS15 fusion gene formation. Study cohort consisted of 33 primary acute leukemia (AL) cases including 6 newly diagnosed and 27 patients previously described in literature. Among study group patients t(1;11)(p32;q23) was found most frequently in infant AL cases (median age 8 months). In acute lymphoblastic leukemia (ALL) male/female ratio was 1:3, in acute myeloid leukemia (AML) it was 1:1. Additional cytogenetic aberrations in 38 % of patients were revealed. The most frequent breakpoint position in EPS15 gene was intron 1. Four different types of MLLEPS15 fusion gene transcripts were detected. Primers-probe-plasmid combination for MLL-EPS15 fusion gene transcript monitoring by realtime quantitative polymerase chain reaction (RQ-PCR) was developed and successfully applied. In 3 patients RQ-PCR was done on genomic DNA for absolute quantification of MLL-EPS15 fusion gene. High qualitative concordance rate (92 %) was noted between minimal residual disease data obtained in cDNA and genomic DNA for MLL-EPS15 fusion detection.
Aim of the study – characterization of immunophenotype in infant acute myeloid leukemia (AML). 90 patients (40 boys and 50 girls) with acute leukemia (AL) aged up to 365 days were included in the current study. AML was found more frequently in infants than in older children (26.67 % and 10.83 % respectively; p = 0.0002). Significant immunophenotypic differences were observed in patients with and without MLL gene rearrangements. Number of cases in those tumor cells expressed CD99, CD61, CD133, CD15, NG2 varied between MLL-positive and MLL-negative groups. CD61-negativity, high CD99, CD15, CD133 and NG2 expression were immunophenotypic signatures of MLLrearranged infant AML, although CD99 and NG2 had the highest diagnostic efficacy. Thus infants’ AML immunophenotype differs significantly due to the presence of MLL gene rearrangements. Diagnostic immunophenotyping of infants’ AML allows predicting presence of MLL rearrangements by either CD99 or NG2 expression.
The estimation of immediate and long-term results after splenectomy depending on indications and contra-indications for 18 primary myelofibrosis (PMF) patients was shown. The reduction of intra- and postoperative complications in PMF patients was noted if the operation was
performed under strict indications and also with prophylactic heparin therapy. Life expectancy is extended after splenectomy during subsequent
relevant specific treatment.
Cytomegalovirus (CMV)-related complications remain an extremely serious and urgent problem in immunocompromised patients. Ganciclovir (GCV) is efficient for the treatment of CMV-infection, but myelotoxicity limits the possibilities of their application. In addition, prolonged or intermittent courses of antiviral drugs predispose to the development of CMV drug-resistant strains. Valganciclovir is a safe and effective alternative to intravenous GCV. Despite the well-spread application of effective methods of early detection and pre-emptive treatment, the issue of the control of CMV-infection is not resolved. High intensive immunoablative therapy (alemtuzumab, ATG, еtс.) and hematopoietic stem cell transplantation (HSCT) from alternative donors greatly increase the risk of life-threatening visceral CMV-infections in patients. Thereby, studies of new therapeutic approaches (for example, transfusion of CMV-specific T-cells) are actually in process.
Mucormycosis (zygomycosis) is a frequently fatal fungal infection in immunocompromized patients. We describe a case of a successfull treatment of pulmonary mucormycosis in 11-year-child with a very severe aplastic anemia. The diagnosis of invasive mycosis has been proved according to EORTC 2008 criteria. Computed tomography showed bilobar right-sided pulmonary infiltration. Lichtheimia corymbifera cultured from BAL. The child achieved complete clinical, laboratory and instrumental response on long-term amphotericin B lipid-formulated therapy combined with posaconazole.
PHARMACOTHERAPY
Biologics are large protein or polypeptide molecules produced by living organisms, which largely determine the efficiency of modern anticancer
therapy. Biological products that destroy cancer cells and protect normal patient tissue led to progress in the treatment of breast cancer, colon cancer, kidney cancer, malignant lymphomas and other diseases. But the high cost and complexity of production limit their use. The expiration of patent protection for a number of biological products resulting to the possibility of reduces their costs when issuing an alternative manufacturer. At the same time, biosimilars are produced by living cells (as the original protein molecules), which led to serious difficulties in reaching their identity. The European Union has developed special registration rules for these preparations in order to avoid lack of efficacy or increased toxicity. They include regulations to determine the quality of biological products, requirements for pre-clinical and clinical studies, according to its specific characteristics, as well as the requirements for pharmacovigilance. Implementation of such a strategy has to register in the EU several biosimilars of granulocyte colonytimulating factor. For one of them – Zarzio – in several clinical studies fully comparable efficacy and tolerability with the original preparation was shown, thus providing a significant reduction of treatment cost with equal efficacy and toxicity.
NEW TRENDS IN MEDICAL SCIENCE
Fullerene derivatives superfamily attracts a serious attention as antiviral and anticancer agents and drug delivery carriers as well. A large number of such fullerene С60 derivatives obtained to date. However, there is an obvious deficit of information about causes and mechanisms of immediately and long-term consequences of their effects in vivo which is a true obstacle on the way leading to practical medical use of them. First, this concerns their impact on the proliferation, apoptosis and necrosis regulation. Fullerene nanoparticle functionalization type, their sizes and surface nanopathology are of great importance to further promoting of either cytoprotective or cytotoxic effects. This lecture provides modern concept analysis regarding fullerenes effects on apoptosis pathway in normal and tumor cells.
ISSN 2413-4023 (Online)