Leczenie zespołów mielodysplastycznych wysokiego ryzyka u dorosłych wg rekomendacji

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

Postępy w leczeniu dorosłych chorych na ostre białaczki

Significant progress has been made within the last years in elucidating and understanding the molecular pathogenesis of acute leukemias and for identifying factors predictive of outcome. Such achievements have thereby provided new opportunities for developing innovative and more effective drugs. There is also evidence that improving the quality of remission can reduce the risk of relapse. New and more effective induction strategies of increasing the daunorubicin dose, introducing antibody-directed chemotherapy and alternative nucleoside analogs may displace the longstanding standard 3 + 7 chemotherapy in patients aged below 60 years suffering acute myeloid leukemia (AML). An unexpected recent finding has been that complete remission in elderly AML patients may not necessarily translate into an overall survival advantage. Hypomethylating agents have demonstrated survival benefit without any improvement in remission rate. The prognosis of adults with acute lymphoblastic leukemia (ALL) is still not satisfactory and adult ALL still remains a challenging disease. Novel methodologies, including new molecular therapeutic targets, immunotherapy with monoclonal antibodies or CAR lymphocytes are very promising for improving ALL patient prognosis. This paper provides a summary review of current insights into new therapeutic strategies for acute leukemias.W ostatnich latach dokonał się istotny postęp w zrozumieniu molekularnych mechanizmów patogenezy ostrych białaczek oraz poznaniu nowych czynników prognostycznych. Wiedza ta stworzyła podstawy do rozwoju nowoczesnych leków i bardziej skutecznych metod leczenia. Istnieją dowody na to, że poprawa jakości remisji wiąże się z obniżeniem ryzyka nawrotu białaczki. Nowe strategie leczenia indukującego związane z eskalacją dawek daunorubicyny, dołączeniem analogów nukleozydowych lub przeciwciał monoklonalnych charakteryzują się wyższą skutecznością niż standardowa chemioterapia 3 + 7 u chorych na ostre białaczki szpikowe (AML) poniżej 60. roku życia. Odmiennie jest u starszych chorych leczonych mniej intensywnie uzyskanie całkowitej remisji nie jest dobrym surogatem całkowitego przeżycia. Wykazano, że leki hipometylujące istotnie wydłużają przeżycie chorych na AML, bez istotnej poprawy odsetka remisji. Rokowanie chorych na ostrą białaczkę limfoblastyczną (ALL) u dorosłych jest nadal niezadowalające, a leczenie tej grupy chorych stanowi wyzwanie dla współczesnej medycyny. Nowe technologie medyczne, w tym terapie celowane i immunoterapia przeciwciałami monoklonalnymi lub limfocytami CAR, są niezwykle obiecujące i dają wielkie nadzieje na poprawę rokowania w ALL u dorosłych. W pracy przedstawiono krótki przegląd nowych strategii leczniczych stosowanych u chorych na ostre białaczki w ostatnich latach

Prophylaxis and treatment of invasive fungal infections in neutropenic patients according to ECIL-3 recommendations

Zmieniająca się epidemiologia inwazyjnych zakażeń grzybiczych (IFI) oraz powszechna dostępność nowych leków przeciwgrzybiczych stwarzają potrzebę opracowania jednorodnych standardów profilaktyki i leczenia zgodnie z zasadami medycyny opartej na faktach. W pracy przedstawiono aktualne wytyczne dla profilaktyki i leczenia IFI u chorych z neutropenią na podstawie zaleceń 3rd European Conference on Infections in Leukemia. Hematologia 2011; 2, 2: 140–148The changes in the epidemiology of invasive fungal infections (IFI) as well as the availability of new antifungal drugs create the need for universal guidelines for IFI prophylaxis and treatment in accordance with principles of evidence based medicine. In this paper we reviewed the updated standards for prophylaxis and treatment of IFI in neutropenic patients according to 3rd European Conference on Infections in Leukemia recommendations. Hematologia 2011; 2, 2: 140–14

Diagnosis recommendation of myelodysplastic syndromes in adults according to European LeukemiaNet

Myelodysplastic syndromes (MDS) according to WHO definition are a group of myeloid neoplasms characterized by peripheral blood cytopenias and increased risk of leukemic transformation. An accurate diagnostic procedure and risk assessment are necessary for choosing an optimal treatment option. The aim of this article is performance of MDS diagnostic standards according to European LeukemiaNet. MDS diagnosis should be based on WHO 2008 criteria with International Prognostic Score System (IPSS) risk assessment. Additionally, in prospective trials WHO based PSS (WPSS) and Revised–IPSS (R-IPSS) should be performed. Immunophentyping and gene mutation assessment are not mandatory. Moreover, individual patient treatment risk according to age, performance status and comorbidities should be evaluated. The treatment decision is made based on MDS prognostic factors and patient status

Współczesne poglądy na leczenie ostrej białaczki promielocytowej

Acute promyelocytic leukemia (APL) deserves a special place among neoplasms. It is the first neo­plasma which the targeted therapy at the molecular level was used in. The addiction of all-trans retinoic acid to the standard, anthracycline-based chemotherapy has hugely improved the complete remission rate. The use of arsenic trioxide (ATO) has further improved the clinical outcome of relapsed and refractory APL. Recently, many studies have been conducted to investigate the use of ATO as a front-line therapy. The article shows the latest recommendations for the management of APL.Ostra białaczka promielocytowa (APL) zajmuje szczególne miejsce wśród nowotworów. Jest to pierwszy nowotwór, w którym zastosowano terapię celowaną na poziomie molekularnym. Dołącze­nie kwasu all-trans retinowego do standardowej chemioterapii opartej na antracyklinach spowo­dowało znaczny wzrost odsetka uzyskiwanych całkowitych remisji. Zastosowanie trójtlenku arsenu (ATO) znacznie poprawiło wyniki leczenia nawrotowych i opornych postaci APL. W ostatnich latach prowadzono wiele badań dotyczących zastosowania ATO jako alternatywnej metody leczenia I linii. W artykule przedstawiono najnowsze zalecenia dotyczące leczenia APL

Znaczenie szlaku SLIT-ROBO w kluczowych dla komórki procesach w warunkach fizjologii i patologii

The SLIT glycoproteins and their roundabout (ROBO) receptors were originally identified as axon guidance molecules that prevent axons from re-crossing the midline. In addition, the SLIT–ROBO interaction is involved in the regulation of cell migration, cell death and angiogenesis. Furthermore, it has a pivotal role during the morphogenesis, controlling the correct development of lung, kidney, liver and breast. The functions which the SLIT–ROBO fulfills during tissue morphogenesis are often dysregulated during cancer development. Therefore inactivation of certain SLITs and ROBOs is associated with advanced tumor formation and progression in disparate tissues. However, some studies revealed that SLIT–ROBO may promote tumor angiogenesis and, consequently, its growth. This review is focused on summarizing the current knowledge about the role of SLIT–ROBO pathway in development of disparate tissues in physiological conditions and in pathogenesis of neoplasms, including hematological malignancies

Acute myeloid leukemia in the elderly people

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

Neuropiliny – budowa, funkcja, rola w powstawaniu nowotworów

Neuropilins are proteins involved in ontogenesis, immunology and cancerogenesis. Neuropilin-1 and its homologue neuropilin-2 are coreceptors that intensify response to different growth factors and other ligands. They are coreceptors for class 3 semaphorines which are involved in axon growth and for a number of proteins belonging to VEGF family. Recently it has been discovered that their activity is much broader. They interact with TGF-β1 and its receptors, hepatocyte growth factor and its receptor, platelet derived growth factor and its receptors, fibroblasts growth factor and integrins. These ligands play a role in angiogenesis and wound healing. In immunology neuropilins are expressed mainly by dendritic cells and regulatory T lymphocytes and they apply mainly inhibitory effect. In neoplasms neuropilins are connected with a poor prognosis which is in accordance with their many interactions with ligands and receptors causing tumor progression