HEMATOLOGIC MALIGNANCIES: DIAGNOSIS, TREATMENT, SUPPORTIVE CARE
Despite significant advances in the treatment of lymphomas in children remain a small proportion of patients with refractory or recurrent disease. An effective approach to the treatment of such patients – not only is the second line chemotherapy, but the use of the new targeted therapies. An example of this approach is the use of brentuximab vedotin (antibody-drug conjugate directed to the CD30) in relapsed Hodgkin’s lymphoma and anaplastic large cell lymphoma. Literature review and own experience of using this drug in children are describes in this article.
In this review we present current state of cytogenetic and molecular genetic diagnostics of various aberrations in infant acute leukemias together with our own experience in this field. A complex characteristic of acute leukemias was performed for both MLL-positive and MLL-negative patients. Genetic heterogeneity was shown. Common and rare cytogenetic and molecular genetic aberrations were presented.
The article contains results of meta-analysis of experience in use of second-generation tyrosine kinase inhibitors – dasatinib. The results of clinical trials dasatinib therapy in chronic myelogenous leukemia imatinib-resistant or intolerant patients are presented. The dasatinib and imatinib comparative analysis in first-line therapy in newly diagnosed chronic myelogenous leukemia patients are demonstrated. The range and frequency of dasatinib therapy adverse events are analyzed. Toxicities management recommendations are listed. Perspectives of dasatinib therapy cessation in patients with long lasting deep molecular responses – treatment free chronic myelogenous leukemia remissions are descripted. Also, there is an information about dasatinib usage in treatment of Philadelphia-positive acute lymphoblastic leukemia.
DNA samples from patients with hairy cell leukemia (HCL) and splenic marginal zone B-cell lymphoma (MZBCL) for BRAF and MAP2K1 activating mutations were analyzed. V600E mutation of BRAF was detected in 39 (98 %) of 40 patients with hairy cell leukemia, and no patient with MZBCL. In none of the patients in this study any other activating mutations than V600E in exons 11 and 15 of BRAF gene were revealed. MAP2K1 Q56P mutation characterized by IGHV4-34 expression was detected in 1 (2 %) of 40 patients with HCL. In none of the patients with MZBCL activating mutations in the 2, 3 or 11 exons of MAR2K1 gene have been identified, including those with IGHV4-34 expression.
The review contains data about new important aspects of pathogenesis, and treatment of anemia of chronic diseases. The treatment of patients with anemia of chronic diseases by erythropoiesis-stimulating agents and iron is analyzed.
HEMATOPOIETIC STEM CELL TRANSPLANTATION
Extracorporeal photopheresis has proved efficacy in the treatment of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation and is an alternative to other treatments. This method is characterized by good tolerability, the lack of age restrictions, minimum of infectious complications compared to increasing immunosuppression. This therapy gives a real improvement
in the quality of life.
Introduction. The role of autologous hematopoietic stem cell transplantation (autoHSCT) in adult patients with acute myeloid leukemia (AML) with poor prognosis factors is not completely defined.
Purpose: to present the results of a multicenter prospective study of autoHSCT efficacy in AML patients with initially unfavorable prognostic factors.
Materials and methods. From 2007 to 2014, 42 patients with primary AML with one or more poor prognosis factors were included in the study. AutoHSCT was performed in 16 patients (9 women) aged 20–57 years (median 38 years) without available compatible allogeneic (related or unrelated) donor. In order to identify the role of different prognostic factors the long-term results were analyzed.
Results. With a median follow up of 49 months (range 5–86 months) 5-years overall survival, event-free survival and relapse-free survival were 47, 47 and 51 %, respectively. Rate of mortality associated with transplantation in 100 days and 2 years after autoHSCT reached 0 and 6 %, respectively. AML relapse was observed in 44 % of patients. Favorable prognostic influence of total body irradiation in conditioning regimens on the overall survival has been identified (р = 0.045).
Conclusion. AutoHSCT in AML patients with initially poor prognosis factors has a long-term anti-tumor effect. In the absence of a fully compatible allogeneic donor, autoHSCT may be considered as an alternative treatment.
BASIC RESEARCH
Hereby we present methodological aspects and prognostic significance of minimal residual disease (MRD) monitoring in infant acute leukemias. Based on our own experience we made algorithm for detection of MRD in this group of patients. We conclude that general concordance between MRD detection by flow cytometry and real-time polymerase chain reaction (PCR) for fusion gene transcripts achieved 87.0 %. Concordance was significantly lower during induction in comparison to consolidation/intensification and relapse treatment (78.6; 90.4 and 93.4 %, correspondingly; p = 0.002). It was not dependent on presence of normal B-cell precursors. Concordance between MRD results obtained by qualitative real-time PCR in bone marrow and peripheral blood samples was 84.5 %. Interestingly, all discrepant results (22 samples 15.5 %) were MRD-positive in bone marrow, but negative in peripheral blood. Despite high qualitative concordance rate between MRD detection in bone marrow and peripheral blood samples we could not show prognostic value of MRD monitoring in peripheral blood by fusion gene transcripts. Multivariate analysis revealed that MRD-positivity at time-point 4 in bone marrow was the only significant and independent prognostic factor of unfavorable outcome in the observed group of patients (hazard ratio 7.326; 95 % confidence interval 2.378–22.565).
The article reviewed literature data relating to the methods used for detection of single tumor cells in bone marrow, lymph nodes, and peripheral blood. Sensitivity of modern detection methods is analyzed. Despite advances in the development of molecular biology and cytology, until now there is no universal approach to the micrometastases identification, and existing methods optimization are recommended.
JUBILEE
ISSN 2413-4023 (Online)