Powikłania infekcyjne i autoimmunologiczne w przewlekłej białaczce limfocytowej

Profound disturbances of different elements of the immune system in chronic lymphocytic leukemia (CLL) lead to impaired elimination of allogeneic antigens, like pathogenic microorganisms, and deficient tolerance of self-antigens, which is responsible for autoimmunological disorders. Susceptibility to infections in CLL patients is due to disease-related immunodeficiency, mainly hypogammaglobulinemia, and aggravated by myelo- and immunosuppressive properties of currently used antileukemic drugs, especially alkylating agents and purine analogues. Severe infections occur in the majority of CLL patients, they may be life-threatening and shortening the patients’ survival. They affect most frequently the respiratory system, and are caused mainly by Gram-positive and Gram-negative bacteria and common viruses like Herpes and Varicella-Zoster. In some patients, especially those treated with purine analogues, opportunistic infections can occur. There are no generally admitted guidelines for the prophylaxis of infections. Vaccinations against influenza and encapsulated bacteria, intravenous immunoglobulins and prophylaxis with cotrimoxazol and antiviral drugs for selected patients under purine analogues or alemtuzumab have been proposed. Autoimmune hemolytic anemia (AIHA) due to the production of anti-erythrocyte autoantibodies is the most common autoimmunological complication of CLL, especially in patients with positive direct antiglobulin test (DAT). It can be also triggered by alkylating agents and purine analogues. The treatment of AIHA includes corticosteroids, rituximab, immunosuppressive agents and splenectomy. Autoimmune thrombocytopenia, pure red cell aplasia, autoimmune neutropenia and non-hematological autoimmune manifestations can also occur.     

Małopłytkowość – wskazania do zastosowania cytokin płytkotwórczych

The most common cause of isolated thrombocytopenia is primary immune thrombocytopenia (ITP). For patients failing initial corticosteroid-based treatment and with refractory ITP post-splenectomy, thrombopoietin receptor agonists are indicated. Two of this thrombopoiesis-stimulating agents have been approved for use in ITP – eltrombopag, formulated for oral administration, once a day and romiplostim, which is administered weekly as a subcutaneous injection.     

Terapia przewlekłej białaczki szpikowej – teraźniejszość i wyzwania na przyszłość

Introduction of imatinib to the treatment of chronic myelogenous leukemia (CML) more than a decade ago may be considered as one of the milestones in the history of cancer treatment and oncology. Small molecule inhibitor, which specifically inhibits BCR/ABL oncogenic tyrosine kinase, responsible for malignant transformation of hematopoietic stem cell proved to be unexpectedly effective in the majority of patients and has revolutionized CML therapy. Unfortunately, a significant group of patients develops resistance or is intolerant to the drug which necessitate search for new better drugs. In the last 5 years 2^nd generation inhibitors have been approved (dasatinib, nilotinib and bosutinib), clinical trials are ongoing with ^3rd generation inhibitors (among them ponatinib, active against BCR/ABL with T315I mutation) and allosteric inhibitors. None of the available drugs eliminates leukemia stem cells, which are the roots of the disease, therefore therapy must be continued indefinitely. Since ultimate goal is to cure the disease there are number of trials to eradicate the disease with combination therapies. We may expect that such like imatinib opened new therapeutic horizons in oncology, complete eradication of CML will help to find cure other cancers.     

Rola monocytów w patogenezie przewlekłej białaczki limfocytowej

Chronic lymphocytic leukemia (CLL) is one of the most common leukemias in adults. CLL is characterized by numerous immune disorders leading to the development of infections which have become the major cause of death in this group of patients. According to recent reports, many of immune alterations observed in the course of CLL could be attributed to dysfunctions of monocytes/macrophages and other cells of myeloid linage. In this article, we summarized the data on the role of monocytes and monocyte-derived cells in the pathogenesis of CLL.     

Cytogenetyczne i molekularne uwarunkowania agresywnej postaci przewlekłej białaczki limfocytowej

Chronic lymphocytic leukemia (CLL) mainly affects people older than 60 years. Accumulation of morphologically mature but dysfunctional B-lymphocytes in the bone marrow, lymph nodes and peripheral blood is a characteristic feature of this disease. Chromosomal aberrations are observed in lymphocytes of most CLL patients. Typical alterations include deletions of 13q14 and 11q, trisomy 12, and deletions of 17p. Altered expression of the genes located within involved regions, i.e. microRNA15/16 (13q14.3), ATM (11q22-q23) or TP53 (17p13) may be associated with the development and progression of the disease. Cryptic mutations may also contribute to leukemogenesis. Among others, they affect TP53, NOTCH1, SF3B1 and BIRC genes.CLL is a disease with heterogeneous course. There are two clinical forms – indolent and aggressive. The former is characterized by long time to first treatment and demise usually occurs because of coexisting diseases or is associated with leukemia-dependent immunodeficiency. Rapid clinical course and short overall survival, sometimes in spite of appropriate treatment implementation, is typical for aggressive form of CLL. For patients with this form, the moment of treatment initiation and the choice of first-line therapy are especially important, and depend inter alia on prognostic and predictive factors.Established poor prognostic factors in CLL include chromosomal aberrations, i.e., deletion of 17p or 11q, high ZAP-70 kinase expression, mutations/deletions of TP53, and lack of mutation of immunoglobulin heavy chain variable region genes (IgVH).In this paper we tried to point out the importance of some of the prognostic and predictive factors used routinely in the diagnostic management of CLL. Prognostic and predictive potential of microRNA expression level and recently described cryptic changes in the TP53, NOTCH1, SF3B1 and BIRC3 have also been presented.     

Ostra białaczka szpikowa u osób w wieku podeszłym

The majority of patients with acute myeloid leukemia are elderly. The introduction of new more aggressive treatment regimens with allogeneic stem cell transplantation have resulted in improvement in clinical outcome of younger AML patients, but analogous improvement in older patients has not been realized. There is evidence that AML in elderly represents a biologically distinct disease that is more aggressive and less responsive to chemotherapy. The important task is to use prognostic factors and predictive modeling to distinguish patients who will benefit from intensive remission-induction approaches and allogeneic transplantation and others who should be managed with less aggressive strategies or novel agents.     

Analiza ekspresji genów odpowiedzialnych za rozwój przewlekłej małopłytkowości immunologicznej u dzieci

BackgroundA complex multifactorial dysregulation of immune system, including cytokines and autoantibodies production, and also proteins modification underlay the primary mechanism of immune thrombocytopenia (ITP). Specific genetic profile of ITP patients is presumed, especially those with a long and complex natural history of the disease.Aim of the studyGene expression analysis of VNN1 and PPARγ in children with immune thrombocytopenia.Materials and methodsCandidate genes were identified with microarray cDNA procedure. For the validation of VNN1 and PPARγ expression changes we used qRT-PCR performed comparatively in samples of newly diagnosed ITP (ndITP, n = 16), chronic ITP (cITP, n = 8) and patients without thrombocytopenia (n = 5).ResultsWe analyzed the data of patients, followed for at least 12 months after ITP diagnosis. No significant differences of VNN1 expression profile were found in between groups (p > 0.05). Lower signatures of mean PPARγ normalized expression values were noticed in chronic ITP patients in contrast to newly diagnosed ITP subjects (p = 0.009). Differences between VNN1/PPARγ ratio values found in ndITP group comparing to subjects with progression to cITP were close to statistical significance (p = 0.054).ConclusionsAnalysis of the VNN1 and PPARγ expression profiles utility in children diagnosed with ITP requires further investigation.     

Transplantacje komórek krwiotwórczych w przewlekłej białaczce limfocytowej

Despite the significant progress that has been made in recent years in the treatment of chronic lymphocytic leukemia (CLL), mainly due to the introduction of monoclonal antibodies, allogeneic hematopoietic cell transplantation remains the only method that could potentially cure CLL. However, because of high peritransplant mortality, this method is reserved only for patients with high-risk CLL. Autologous transplantation is currently not recommended for patients with CLL due to the lack of advantage over the standard first-line FCR immunochemotherapy and the lack of efficacy in high-risk CLL.     

Zastosowanie cytometrii przepływowej oraz analizy proteomicznej w ocenie erytrocytarnych białek błonowych podczas przechowywania koncentratów krwinek czerwonych

For over 100 years the erythrocyte cell membrane attracted interest of transfusiologists mainly due to the antigens localized on their surface and associated risks of patient alloimmunisation and therefore the need of serological selection of donor's and recipient's blood. Presently it is known that RBC antigens and other membrane proteins play important transport and protective functions, and are involved in adhesion, maintenance of cell shape and in the process of aging and phagocytosis. Since the available results of retrospective clinical observations suggest an adverse effect of transfusion on selected groups of patients, it is important to undertake studies on the changes taking place within the cell membrane of erythrocytes stored in blood banks. Flow cytometric analysis of stored leucodepleted or non-leucodepleted erythrocyte concentrates, revealed significant changes in the level of expression of many RBC surface molecules: CD44, CD47, CD55, CD58, CD59, CD235a (GPA). In parallel, a significant development of proteomic analysis of stored RBCs is observed. Stored RBCs offer less variability of biological material, caused by drugs, illnesses, etc. when compared with clinical proteomics studies; however, the complexity of the methodology and the lack of uniform and comparable procedures may cause misinterpretation and even create artifacts. Still, modern research methods offer hope for the elaboration of aging biomarkers of stored RBCs as well as for raising the level of transfusion medicine quality.     

Leczenie zespołów mielodysplastycznych wysokiego ryzyka u dorosłych wg rekomendacji European LeukemiaNet

High-risk myelodysplastic syndromes (MDS) are defined by patients who fall into Intermediate-2 or High-risk group categories in the International Prognostic Scoring System or High/Very high in the revised IPSS (R-IPSS). High-risk MDS carry a major risk of progression to acute myeloid leukemia and short survival. Standard therapies include allogeneic stem cell transplantation, induction therapy (AML-like) and hypomethylating agents. This article presents recent European LeukemiaNet recommendations for treatment of high-risk MDS.     

Białaczkowe komórki macierzyste

Acute myeloid leukaemia (AML) is a neoplasm originating in early haematopoietic progenitor cells. Each AML clone contains a subpopulation of leukaemic stem cells (LSCs). LSCs have the capacity to repopulate AML in NOD/SCID mice and regrow leukaemia in patients after remission period. LSCs are characterized by CD34+CD38-Lin-CD33+/-CD123+ immunophenotype. The currently available data show that LSCs play a pivotal role in drug resistance. Many studies and clinical trials are being conducted to eradicate LSCs using different forms of target therapy.     

Długotrwała odpowiedź na leczenie azacytydyną pacjentki z ostrą białaczką szpikową z niekorzystnym profilem cytogenetycznym – prezentacja przypadku

Acute myeloid leukemia (AML) is the most common type of leukaemia found in adults and the number of disease cases increases with age. Despite the advances in the AML treatment, the results in patients over the age of 60 remain unsatisfactory.In this study we present the case of a 73-year-old female patient with an unfavourable cytogenetic profile, in whom we observe long-term response to azacitidine, after previous failures of classic polychemotherapy.In February 2010, a 70-year-old patient was admitted to the Department of Haematology USK in Bialystok on suspicion of AML. The patient was qualified for intensive chemotherapy regimen of daunorubicin (DNR) and cytarabine (Ara-C).Cytogenetic examination revealed the presence of double minutes – acentric fragments of extrachromosomal DNA, which is associated with resistance to standard chemotherapy. Induction chemotherapy was complicated by febrile neutropenia, pneumonia and episodes of atrial fibrillation. Due to the lack of remission and severe after-induction period, a brief reinduction chemotherapy with DNR and Ara-C was applied to obtain complete remission with incomplete regeneration (CRi).Due to the recurrence in October 2010, reinduction chemotherapy was given followed by two cycles of maintenance chemotherapy. After another relapse in February 2011 (23,6% blasts in the bone marrow), a chemotherapy regimen designed for refractory and relapsed leukaemia was given, without any effect. In April 2011, the patient began azacitidine treatment. By the end of March 2013, the patient received twenty-one treatment cycles. The twelfth cycle of chemotherapy was complicated by pulmonary embolism which was treated successfully. The complete blood count remains at normal values.Recent reports indicate a clear relationship processes such as epigenetic regulation of DNA methylation with leukaemogenesis. The use of hypomethylating drugs in AML is yielding promising results.     

Chłoniak grudkowy: rozpoznawanie i leczenie

Follicular lymphoma (FL) is a B-cell lymphoproliferative neoplasm of transformed follicular center B cells. FL is characterized by lymphadenopathy, bone marrow involvement, splenomegaly, and less commonly other extranodal sites of involvement. Diagnosis of FL is based on histology of biopsy of a lymph node along with immunohistochemical staining. In typical cases of FL, lymphoma cells show positive expression of surface antigens such as CD19, CD20, CD10 and monoclonal immunoglobulin, as well as cytoplasmic expression of BCL-2 protein. The majority (80–90%) of cases have the characteristic t(14;18) translocation involving the IgH/BCL2-2 genes.Decision-making to treat in the frontline is based on the algorithms described by the GELF (Group d’Etude des Lymphomes Folliculaires) or BNL (British National Lymphoma) group. The general approach should be immunochemotherapy based on CHOP or CVP regimens, with more recent evidence for the alternative bendamustine. Therapeutic options for relapsed/refractory FL include the same regimens traditionally used for the first-line therapy. Finally, hematopoietic stem cell transplantation (both autologous and allogeneic) remains a useful treatment strategy, although the optimal timing of such approaches requires further clarification.     

Agresywne chłoniaki z obwodowych limfocytów T

Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of relatively rare lymphoid malignancies. In Europe they account for approximately 15% of all lymphomas. Results of treatment of aggressive PTCL are poor and differ significantly from what has been achieved in recent years in the treatment of B-cell lymphomas. Currently, only patients with anaplastic large cell lymphoma ALK (+) have more than 50% chance of long-term survival. CHOP protocol should not be considered a standard of care, however, in the absence of alternatives it is used in clinical practice. Consolidation therapy with autologous haematopoietic stem cell transplantation (ASCT) improves response rate. This review summarizes treatment options for most common aggressive PTCL: anaplastic large cell lymphoma, angioimmunoblastic lymphoma, peripheral T-cell lymphoma NOS, NK/T-cell lymphoma, enteropathy associated lymphoma and hepatosplenic T-cell lymphoma.