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Introduction of tyrosine kinase inhibitors into the treatment of chronic myeloid leukaemia (CML) over the past 25 years has resulted in a revolutionary change and has had a crucial impact on global treatment strategies in oncology. CML has been transformed from a deadly malignancy into a chronic disorder with patients today dying more frequently from other illnesses and patient overall survival equalling that of the general population. As treatment efficacy rises, prevention and management of side effects is of growing importance. The logical next step is an attempt to stop treatment in optimally responding patients with the aim of maintaining treatment-free remission. On the other hand, a small fraction of high-risk patients can still profit from bone marrow transplantation and these patients may profit prospectively from the introduction of new classes of inhibitors acting outside the ABL kinase domain. Cure of CML with targeted conservative treatment has become the long-term aim. This review discusses the developments in CML treatment over the past 25 years with emphasis on the Czech contribution. [ABSTRACT FROM AUTHOR]

Primary myelofibrosis belongs to the group of Ph1-negative myeloproliferative neoplasms, along with essential thrombocythemia and polycythemia vera, which may also progress to a fibrotic stage. Risk stratification of patients is especially important for proper therapeutic decision making and selection of high risk patients suitable for allogeneic stem cell transplantation, the only curative option for myelofibrosis. Transplantation carries a significant risk of mortality and morbidity, therefore it is recommended in patients with a median survival of less than 5 years. The recently introduced Dynamic International Prognostic Scoring System-plus prognostic model uses eight independent predictors of inferior survival. Janus 2 kinase inhibitors present a new targeted therapy affecting pathogenetic signal pathways. The results of on-going studies will show their long-term efficacy, safety and impact on overall survival. [ABSTRACT FROM AUTHOR]

Regulation of gene expression, especially in hematopoietic stem cells, plays an essential role in differentiation and other important processes of haematopoiesis. Pathogenesis of different malignant diseases is characterised by disruption of epigenetic regulation. Certain somatic mutations, including genes such as DNMT3A, TET2, IDH1, IDH2, ASXL1, MLL or EZH2, have been found in acute myeloid leukaemia, especially in patients with normal karyotype AML. These mutations are considered to be pre-leukemic events and are stable indicators of clinical course. In combination with driver mutations, they are suitable markers for monitoring minimal residual disease. Specific mutational profiles of individual patients could provide essential information about disease progression, relapse or achievement of complete remission. The aim of this article is to review current knowledge regarding the clinical and therapeutical value of mutations in selected genes involved in epigenetic regulation of gene expression in acute myeloid leukaemia. [ABSTRACT FROM AUTHOR]

Chronic myelomonocytic leukemia (CMML) is a clonal disorder of hematopoietic stem cell characterized by features of a myelodysplastic syndrome (MDS) and a myeloproliferative neoplasm (MPN). It occurs mainly in older people, mostly in men, and often transforms into acute myeloid leukemia (AML). The most common symptoms of CMML reflect hypercatabolism, the present bicytopenia, (hepato)splenomegaly and organ infiltration with monocytes. It is characterized by absolute monocytosis (> 1 x 109/l) in the peripheral blood that persists longer than 3 months. Cytogenetic examination confirmed the presence of chromosomal aberrations in approximately 40% of cases, but they are not specific for this disease. Nowadays, significant attention is focused on the TET2 gene mutation -- its prognostic significance is not fully understood. JAK2 (V617F) mutation is present mainly in myeloproliferative variant of MP-CMML. The disease has variable clinical course and a very poor prognosis. Although new information from molecular biology of CMML are implemented to the treatment strategy, the results are still unsatisfactory. The objective of this review is to summarize recent information about the disease pathogenesis and the proposal for a treatment algorithm. [ABSTRACT FROM AUTHOR]

We present three cases of patients with myeloproliferative neoplasm that were because of anorexia and weight reduction given megestrol acetate to improve their alimentation and so their life quality. Clinically important reduction of splenomegaly and reduction or loss of transfusion dependence after administration of gestagen were observed as side effect in all patients. After discontinuation the spleen started to grow again, but administration of megestrol has led to its repeated diminution. This is the first description of the important ,,side effect" of megestrol in patients with myeloproliferative neoplasms and prominent splenomegaly. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Classification and diagnosis of myeloproliferative neoplasms: The 2008 World Health Organization criteria and point-of-care diagnostic algorithms" that was published in a previous issue.

We describe case of 34-year old man after autologous stem cell transplantation. He was examined because of fever, progression of right tonsil size, cervical lymphadenopathy, cough, neck pain, dyspnoea about 4 months after transfer of stem cells. Progressively movement dysfunction of right upper limb, urine retention, organic brain syndrome with attacks of somnolence alternate with attacks of anxiety were developed. On whole body PET/CT scan was accumulation of FDG in irregular condensations in both lung sides. Results of cultivation from peripheral blood and BAL were negative repetitively. Two demyelinating lesions were described on MRI of brain. PCR positivity of Toxoplasma was proved in cerebrospinal fluid. Extinction of aliments and health of the patient was improving during targeted antitoxoplasmic therapy. Nowadays, almost 6 years after stem cell transplantation, patient is still in complete remission of lymphoma without any consequence of toxoplasmic infection. [ABSTRACT FROM AUTHOR]

Introduction. Current curative treatment of acute myeloid leukemia is based on intensive chemotherapy and hematopoietic stem cell transplantation with a significant risk of severe adverse effects, including leukemogenic and cancerogenic ones. Objectives. The study is aimed at assessing of incidence and types of malignant tumours in successfully treated acute myeloid leukemia patients. Methods. A retrospective analysis consists of 256 patients diagnosed with acute myeloid leukemia at the Department of Hemato-Oncology in Olomouc in 1996-2008 who were treated with intensive chemotherapy and achieved complete remission of the disease. Results. Second malignancy occurred in 11 individuals (4.3%) after successful treatment of acute myeloid leukemia. Observed age-standardized incidence of these tumours, 8.29/1,000 person-years, 95% Cl = (2.99; 13.58), was not significantly different from the incidence in population. Five patients died of the second malignancy. [ABSTRACT FROM AUTHOR]

Retrospective analysis of 54 adult patients with chronic myeloid leukemia in chronic phase treated with imatinib mesylate (IM) in first line is focused on evaluation of prognostic value of early molecular response after 3 months therapy as a predictive landmark of rate achievement optimal IM response. Treatment response was evaluated in cytogenetic and molecular analysis with application of European LeukemiaNet (ELN) 2009 criteria. The follow-up was 12 to 95 months (median 37 months). Estimated progression-free survival (PFS), event-free survival (EFS) and overall survival (OS) at 5 years were 80%, 71% a 89%. At 18 months, cumulative incidence of complete cytogenetic response (CCyR) and major molecular response (MMR) were 81% and 56%, respectively. According to ELN criteria; 32 patients (59%) achieved an optimal and 13 patients (24%) had a suboptimal response while 9 patients (17%) failed IM. Patients were divided into 3 categories according to the results of BCR-ABL transcript levels after 3 months IM therapy: ≤ 1,0% (12 patients), > 1,0 to ≤ 10% (26 patients) and > 10% (16 patients). Comparing these groups of patients it was revealed that patients with lower BCR-ABL (IS) levels after 3 months IM therapy had a significantly higher probability of subsequently obtaining a CCyR (p<0.0001) and MMR (p<0.0001) than patients with higher transcript levels. When we evaluated IM response according to the ELN criteria it was demonstrated that the degree of molecular response after 3 months determined patients quickly achieved optimal treatment response. Early evaluation of molecular response after 3 months of IM therapy in patients with CML can identify patients who early achieve CCyR and MMR. [ABSTRACT FROM AUTHOR]

The studied group comprises 80 young patients with AIM on dual antiplatelet therapy with acetylsalicylic acid (ASA) and thienopyridines. Antiplatelet therapy was monitored by platelet-rich plasma light transmittance aggregometry using the APACT 4004 analyser (Helena Laboratories, Austria) and by whole blood impedance aggregometry using the Multiplate analyser (Dynabyte, Germany). Platelet aggregation was detected after stimulation with arachidonic acid for the detection of aspirin resistance and with ADP and prostaglandin E1 for the detection of thienopyridine resistance. To determine the frequencies of P2Y12 (i-744T>C; rs2046934), P2Y12 (34C>T; rs6785930) and COX-1 (- 842A>G; rs10306114) polymorphisms, DNA of patients with AIM was tested by RT-PCR and melting curve analysis using the LightCycler 480 analyser (Roche Diagnostics, Germany).The cut-offs for patients with effective ASA therapy are 25% of aggregated platelets and 220 AUC/min respectively if LTA or MEA is used. The cut-offs for effective thienopyridine therapy are 45% of aggregated platelets or 298 AUC/min, respectively.The aim of our work was to use the two aforementioned functional laboratory methods to assess both aspirin and thienopyridine resistance and to determine the contribution of platelet receptor genetic polymorphisms to resistance to antiplatelet therapy in AIM. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of non-Hodgkin lymphomas in Western countries. Implementation of immunotherapy using monoclonal antibodies to therapeutic protocols has led to dramatic improvements in overall survival. DLBCL became a model of a successful immunochemotherapy concept. Despite this fact, there is still a proportion of patients who do not respond to or relapse early after treatment. Growing evidence suggests that host antitumor immunity is suppressed by lymphoma cells in many ways. First, host cytotoxic T cells are directly suppressed by interaction with programmed cell death (PD) ligand on lymphoma cell surface and a similar mechanism enhances the activity of suppressive regulatory T cells (Tregs). Second, tumor cells escape host cytotoxic cells due to lower immunogenicity caused by reduced expression of HLA antigens. Both mechanisms have an origin in primary genetic events in lymphomagenesis. Rearrangement of MHC class II transcriptional activator (CIITA) gene and amplification of Janus kinase (JAK2) gene lead to enhanced expression of PD ligands 1 and 2, higher proliferation activity, and lower expression of HLA. This paper summarizes current knowledge about clinically relevant immune escape mechanisms in DLBCL. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is characterized by distinct clinical and genetic heterogeneity. Chromosomal aberrations are present in about 55% of patients at the time of diagnosis however a large group of AML (about 45%) comprise patients with normal karyotype (NK-AML). In the latter group, gene mutations and changes in expression profiles enable us to allocate subsets with different prognosis. In NK-AML specific mutation profiles are associated with worse prognosis (FLT3-ITD, MLL-PTD mutations) or mark for better prognosis (isolated NPM1 and CEBPA mutations, NPM1mutated AML without FLT3-ITD). Treatment decisions based on molecular stratification however, remain controversial. This review assesses the current insight on the prognostic and therapeutic significance of gene mutations in NK-AML. [ABSTRACT FROM AUTHOR]

The bone marrow transplantation is a curative method in leukemia, lymphomas, immunodeficient states and solid tumors. Graft versus host disease (GVHD) is a significant complication in patients after bone marrow transplantion, most frequently affected of intestine, liver, skin and oral mucosa. Oral mucosa damage is presented by chronic and acute form of GVHD. The acute form is presented by painful ulcers, lichenoid lesions affecting practically whole oral cavity, while the chronic GVHD is compared to autoimmune diseases such as Sjogren syndrome. GVHD is a major complication of bone marrow transplantation with risk to health a therapeutic result. The treatment is long-term and involve interdisciplinary cooperation. [ABSTRACT FROM AUTHOR]

Comparative genomic hybridization (CGH) was carried out in 30 mantle cell lymphoma (MCL) patients at the time of diagnosis. CGH results were supported by conventional cytogenetics (CC), FISH, molecular genetic PCR methods and 2 patients were examined by array CGH. Using all cytogenetic, molecular cytogenetic and PCR methods, chromosomal changes were detected in 28 (93%) patients. Using CGH, unbalanced chromosomal changes were detected in 24 (80%) cases. The most frequent aberrations were losses of 1p (8 cases), 8p (10 cases), 9q (6 cases), 11q (11 cases), 13q (10 cases) and 17p (9 cases), and gains of chromosome 3 and 3q (12 cases) and 8q (7 cases). Total number of 60 gains and 116 losses were detected. The primary chromosomal change t(11;14) was detected using FISH and/or PCR in 20 (66.6%) patients, and in 9 of them, the breakpoint was determined using PCR in the major translocation cluster (MTC). The evaluation of the frequencies of CGH changes in groups of patients with and without t(11;14) revealed the differences only in losses 6q and 9q, which were only found in patient with t(11;14). An important result was obtained using array CGH method. In a patient without the primary t(11;14), the gain of CCND1 gene was found. Our results show high heterogeneity of the additional chromosomal changes in MCL cases, which involved specific chromosomal subregions. We did not confirm the importance of subdividing of MCL cases with and without t(11;14). Also, statistical significance in survival rates between both subgroups was not confirmed. [ABSTRACT FROM AUTHOR]

Cytogenetic and molecular cytogenetic analysis of 79 childhood acute lymphoblastic leukemias (ALL) revealed chromosomal abnormalities in 76 (96%). Complex karyotypes (a finding of three and more chromosomal aberrations in a karyotype) were identified in 21 (26.6%) out of 79 patients. In 11 patients, complex karyotypes have included common recurrent chromosomal abnormalities, such as translocation t(12;21) in seven cases, t(9;22) in two cases, one case with t(2;1;19) and another one with translocation involving 11q23. In 10 patients, miscellaneous abnormalities were detected. Five patients displayed hyperdiploidy (47∼57 chromosomes), three patients complex karyotypes with deletions of 9p, one patient with two new complex translocations t(2;4;12;13) and t(7;11;20), and the last patient with dic(12;21). The evaluation of the frequency of the chromosomal breaks (>5 per chromosome) showed that chromosomes 2, 4, 5, 7, 9, 12, 13, and 21 were most frequently affected. Survival analysis revealed statistically significant unfavorable event-free survival (EFS) (P = 0.013) and decreased overall survival in the group with complex karyotypes (n = 21) compared with the other cases (n = 58). The evaluation of overexpression profile revealed increased occurrence of double CD13/CD33 positivity in patients with common recurrent chromosomal abnormalities (in 70% of cases); no such cases were registered in the other group (P<0.01). [Copyright &y& Elsevier]

Reports on the detection of double fusion signal BCR/ABL by fluorescence in situ hybridization (FISH) on chromosomes 9 and 22 in a child with acute lymphoblastic leukemia (ALL). Detection of Ph chromosome by classical cytogenetics; Factors that are associated with Ph chromosomes suffering from All; Reasons for using FISH method.