Novosti u liječenju zloćudnih bolesti mijeloidnih stanica

Molecular defects discovered in the recent years could explain the pathogenesis of myeloid malignancies. Moreover these alterations serve as the targets for the therapy. In this article treatment approach of myeloid malignancies is presented, together with the new treatment possibilities specifically acting on the level of molecular defects. Therapy with the combination of several agents which target more than one molecular alterations i.e. gene mutation, signal transduction pathway or antigenic determinant may be the most promising therapy in the future.Nedavno otkrivenim molekularnim oštećenjima moguće je objasniti patogenezu zloćudnih bolesti mijeloidnih stanica. Te su promjene usto i ciljevi prema kojima se usmjerava terapija. U ovom članku prikazan je pristup u liječenju zloćudnih bolesti mijeloidnih stanica te nove mogućnosti liječenja s djelovanjem na razini molekularnih oštećenja. Terapija kombinacijom nekoliko lijekova koji ciljaju više od jedne molekularne promjene, npr. gensku mutaciju, prijenos signala ili antigensku determinantu najviše obećava i mogla bi u budućnosti dati najbolje rezultate

FNA based diagnosis of head and neck nodal lymphoma [Citomorfološka dijagnoza limfoma u području glave i vrata]

Fine-needle aspiration (FNA) biopsy has become a well established technique in the diagnosis, staging, and follow-up of patients with head and neck lesions. As in lymphoma diagnostics, FNA serves as a screening method in evaluating potentially affected lymph node for open or core biopsy. According to the World Health Organization classification of lymphoid neoplasms, today it is important to recognize cell morphology and reveal its phenotype, then combine it with different genotypic information and clinical data to provide appropriate therapy. The aim of this study was to assess the efficacy of FNA and immunocytochemistry based lymphoma diagnostic in head and neck region. We conducted a retrospective study during a period of three years where cases with either FNA diagnosis or clinical suspicion of newly recognized or relapsing lymphoma were reviewed. In the study were included patients that were referred to our laboratory from hematology department, in whom head and neck lymphadenopathia was found and lymph node FNA preceded other procedures. Two hundred eighty-five aspirations from 248 patients fulfilled study criteria. Adequate specimens were diagnosed as lymphoma in 100 cases (36%), in 65 male and 35 female patients, 76 in patients with newly discovered disease and 24 in patients with prior lymphoma diagnosis. Overall sensitivity of FNA specimens in the diagnosis of head and neck lymphomas was 90%, specificity 88%, predictive value of a positive result 97%, and predictive value of negative result 61%. Based on our results FNA corroborated with immunophenotyping by immunocytochemistry can be method of choice in primary lymphoma diagnosis as a method complementary to histopathology in lymphoma diagnostics

Collection and composition of autologous peripheral blood stem cells graft in patients with acute myeloid leukemia: influence on hematopoietic recovery and outcome [Skupljanje i sastav transplantata autolognih krvotvornih matičnih stanica periferne krvi u bolesnika s akutnom mijeloičnom leukemijom: utjecaj na hematološki oporavak i ishod]

Hematopoietic stem cell (HSC) transplantation is a standard approach in the treatment of hematological malignant diseases. For the last 15 years the main source of cells for trasplantation have been peripheral blood stem cells (PBSC). With the availability of hematopoietic growth factors and understanding the advantages of treatment with PBSC, the application of bone marrow (BM) was supplanted. The aim of this survey was to explore the success of PBSC collection, the factors which influence the success of PBSC collection, the composition and the quality of graft and their infuence on hematopoietic recovery and outcome after transplantation in patients with acute myeloid leukemia (AML). PBSC were collected by the method of leukapheresis after applying a combination of chemotherapy and growth factors or only growth factors. The quality of graft was determined with the clonogenic progenitor cell assay and with the flow citometry analysis. Of the total 134 patients with AML, who were submitted to HSC mobilization, the collection was successful in 78 (58.2%) patients. The collection was more successful after the first than after the second attempt of HSC mobilization (49% vs. 11%). The criteria for effective mobilization were the number of leukocytes >3´109/L and the concentration of CD34+ cells >20´103/mL in the peripheral blood on the first day of leukapheresis. The number of CD34+ cells infused had the strongest impact on hematopoietic recovery. We noted significantly faster hematological recovery of neutrophils and platelets, fewer number of transfused units of red blood cells and platelets, shorter duration of the tranfusion support, shorter treatment with intravenous antibiotic therapy and shorter hospitalization after PBSC compared to BM transplantation. These advantages could provide their standard application in the treatment of patients with AML

Molecular Genetics - the Future of Oncology

U radu su prikazane nove spoznaje o mehanizmu nastanka zloćudnih tumora na molekularnoj razini. Raspravlja se o onkogenima koji mogu mijenjati signalni put stimulacije rasta stanice od receptora na membrani preko unutarstaničnoga signalnog puta do transkripcijskih faktora jezgre. Nesvrhoviti tumorski rast može biti posljedica i poremećene funkcije tumorski supresorskih gena i apoptoze. U drugom dijelu rada naglašene su velike mogućnosti molekularnih tehnika u dijagnostici zloćudnih tumora. Posebice se naglašava tehnika genskih čipova koja predočuje gensku ekspresiju. Preliminarni rezultati pokazuju da nove tehnike genske ekspresije mogu značajno unaprijediti klasifikaciju zloćudnih tumora. Molekularna klasifikacija primarno polazi od prognoze bolesti. Jedan od primjera vrijednosti molekularne klasifikacije je podjela difuznih B-velikostaničnih limfoma. Tehnikom genskih čipova ti limfomi pokazuju dvije slike različite prognoze.New insights of molecular mechanisms on the biology of cancer are reported. The possible mechanism and disturbance of signaling pathways for cell growth important for cancer transformation is discussed. Perturbations and oncogene mutations of signal transduction in cancer disturbance might be changed by the cell membrane receptor, intracellular signaling and nuclear transcriptional factors. Mutation of tumor suppressor genes and deregulation of apoptosis are also important in cancerogenesis. In the second part of the text the new molecular techniques important for diagnosis and prognosis of cancer are described. cDNA microarrays are a new tool to analyzy gene expression patterns in human cancer. Molecular classification of tumors into general categories of gene expression can potentially identify previously undetected and clinically significant subtypes of cancer. The first major clinical correlation of gene expression patterns with disease outcome was documented in diffuse large B-cell lymphoma. By gene-chip arrays this lymphoma is divided into two molecularly distinct forms with different survival

New Classification of Hematopoietic Malignancy

U radu je predočena nova podjela krvotvornih zloćudnih bolesti prema Svjetskoj zdravstvenoj organizaciji. Podjela polazi od krvnih loza te uključuje novu skupinu limfoproliferativnih bolesti nakon presađivanja tkiva i organa. Nova podjela uključuje prognostičke čimbenike te relevantne kliničke pokazatelje.A new classification of hematopoietic malignancy according to World Health Organization is reported. In this classification myeloid and lymphoid malignancies as well as malignant tumours of mastocyte and histocyte and dendritic cells are included. A new group of lymphoproliferative diseases following organ and tissue transplantation is recognized. Clinical and prognostic factors are the most relevant factors which determine new WHO classification

High-dose ifosfamide and mitoxantrone (HDIM) in patients with relapsed or refractory Hodgkin's lymphoma

Relapsed/refractory Hodgkin's lymphoma (HL) is treated with salvage chemotherapy and autologous stem cell transplantation (ASCT). Optimal chemotherapy is unknown. We retrospectively analyzed outcomes of 58 patients treated with 2 cycles of high-dose ifosfamide and mitoxantrone (HDIM). HDIM consisted of ifosfamide 5 g/m(2)/day and MESNA 5 g/m(2)/day in continuous 24-h infusion (days 1 and 2), MESNA 2.5 g/m(2) over 12 h (day 3), and mitoxantrone 20 mg/m(2) (day 1) administered every 2 weeks. Stem cells were collected after the first cycle. Responding patients proceeded to ASCT. Toxicity was acceptable. Stem cell mobilization was successful in 96 % of patients. Overall response rate was 74 % (89 % in relapsing and 45 % in refractory patients) with 31 % complete remissions. After a median follow-up of 54 months, 5-year event-free survival was 56 % (69 % for relapsing and 35 % for refractory patients), and 5-year overall survival was 67 % (73 % for relapsing and 55 % for refractory patients). Significant adverse prognostic factors were refractoriness to previous therapy and HDIM failure. No differences in outcomes were noted between patients with early and late relapses or between complete and partial responders. HDIM is a well-tolerated and effective regimen for relapsed and refractory HL with excellent stem cell mobilizing properties. Patients failing HDIM may still benefit from other salvage options

Collection and Composition of Autologous Peripheral Blood Stem Cells Graft in Patients with Acute Myeloid Leukemia: Influence on Hematopoietic Recovery and Outcome

Hematopoietic stem cell (HSC) transplantation is a standard approach in the treatment of hematological malignant diseases. For the last 15 years the main source of cells for trasplantation have been peripheral blood stem cells (PBSC). With the availability of hematopoietic growth factors and understanding the advantages of treatment with PBSC, the application of bone marrow (BM) was supplanted. The aim of this survey was to explore the success of PBSC collection, the factors which influence the success of PBSC collection, the composition and the quality of graft and their infuence on hematopoietic recovery and outcome after transplantation in patients with acute myeloid leukemia (AML). PBSC were collected by the method of leukapheresis after applying a combination of chemotherapy and growth factors or only growth factors. The quality of graft was determined with the clonogenic progenitor cell assay and with the flow citometry analysis. Of the total 134 patients with AML, who were submitted to HSC mobilization, the collection was successful in 78 (58.2%) patients. The collection was more successful after the first than after the second attempt of HSC mobilization (49% vs. 11%). The criteria for effective mobilization were the number of leukocytes >3´109/L and the concentration of CD34+ cells >20´103/mL in the peripheral blood on the first day of leukapheresis. The number of CD34+ cells infused had the strongest impact on hematopoietic recovery. We noted significantly faster hematological recovery of neutrophils and platelets, fewer number of transfused units of red blood cells and platelets, shorter duration of the tranfusion support, shorter treatment with intravenous antibiotic therapy and shorter hospitalization after PBSC compared to BM transplantation. These advantages could provide their standard application in the treatment of patients with AML

FNA Based Diagnosis of Head and Neck Nodal Lymphoma

Fine-needle aspiration (FNA) biopsy has become a well established technique in the diagnosis, staging, and follow-up of patients with head and neck lesions. As in lymphoma diagnostics, FNA serves as a screening method in evaluating potentially affected lymph node for open or core biopsy. According to the World Health Organization classification of lymphoid neoplasms, today it is important to recognize cell morphology and reveal its phenotype, then combine it with different genotypic information and clinical data to provide appropriate therapy. The aim of this study was to assess the efficacy of FNA and immunocytochemistry based lymphoma diagnostic in head and neck region. We conducted a retrospective study during a period of three years where cases with either FNA diagnosis or clinical suspicion of newly recognized or relapsing lymphoma were reviewed. In the study were included patients that were referred to our laboratory from hematology department, in whom head and neck lymphadenopathia was found and lymph node FNA preceded other procedures. Two hundred eighty-five aspirations from 248 patients fulfilled study criteria. Adequate specimens were diagnosed as lymphoma in 100 cases (36%), in 65 male and 35 female patients, 76 in patients with newly discovered disease and 24 in patients with prior lymphoma diagnosis. Overall sensitivity of FNA specimens in the diagnosis of head and neck lymphomas was 90%, specificity 88%, predictive value of a positive result 97%, and predictive value of negative result 61%. Based on our results FNA corroborated with immunophenotyping by immunocytochemistry can be method of choice in primary lymphoma diagnosis as a method complementary to histopathology in lymphoma diagnostics

Adult acute myeloid leukemia: diagnosis and treatment

Akutna mijeloična leukemija (AML) bolest je koja je posljedica heterogenog klonalnog poremećaja hematopoetske matične stanice. AML je bolest starijih ljudi, a medijan godina kada se pojavljuje je 67. U posljednjih nekoliko godina istraživanja u području molekularne biologije bila su krucijalna u razlučivanju patofiziologije bolesti. Genetičke abnormalnosti spadaju među najvažnije čimbenike o kojima ovisi odgovor na terapiju i ishod bolesti, te je njihovo detaljno razumijevanje potrebno za razvijanje novih terapijskih mogućnosti. Iako je značajan napredak postignut u liječenju mladih ljudi, liječenje bolesnika starije životne dobi je i dalje nezadovoljavajuće. Sadašnja klinička istraživanja imaju fokus na razvijanje ciljane terapije.Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hematopoietic progenitor cells. AML is a disease of elderly people with the median age of presentation being 67 years. In the past few years, research in molecular biology has lead to a better understanding of the disease pathophysiology. Genetic abnormalities are one of the most important factors which determine the disease outcome and response to chemotherapy, and their better understanding is needed for development of new treatment approaches. Although significant advances have been made in treatment of younger patients, results of the treatment in the elderly is still unsatisfactory. Current clinical trials are focused on target therapy development