Szpiczak plazmocytowy wysokiego ryzyka

Multiple myeloma is a very heterogeneous disease. Though distinctive, several subgroups of the disease have been identified basing on pathological and clinical features. It is generally accepted that high risk myeloma could be defined as a subtype of disease leading to death within 24 months. Many prognostic parameters help to identify high risk myeloma including age, renal insufficiency, comorbities, proliferation activity and genetic abnormalities. Basing on selective prognostic factors, some risk stratification and risk adapted therapies were proposed by European and American study groups, but the results of therapy are still unsatisfactory. It is suggested that patients with high risk myeloma should probably benefit from dose-dense and prolonged therapy including novel drugs being in the clinical trials

Myeloma multiplex - new targets of treatment

Szpiczak mnogi (plazmocytowy) jest chorobą polegająca na proliferacji atypowych plazmocytów. Bardzo istotną rolę w progresji szpiczaka odgrywa mikrośrodowisko szpiku i kontakt komórek szpiczakowych z komórkami śródbłonka naczyń. Angiogeneza jest objawem patomorfologicznym procesu nowotworowego, a podścielisko szpiku kostnego tworzy warunki sprzyjające proliferacji komórek szpiczakowych, zapobiegając apoptozie oraz utrudniając dostęp leków cytostatycznych.Myeloma multiplex (plazmocytoma) is determinated by proliferation of atypical plasma cells. Microenvironment of bone marrow and contact of myeloma and endothelial cells play an important role in myeloma progression. Angiogenesis is a pathomofphological symptom of cancerogenesis and bone marrow stroma promotes proliferation of myeloma cells, prevents their apoptosis and impedes cytostatics acces

Angiogenesis and antiangiogenic treatment in plazmocytoma

Angiogeneza odgrywa kluczową rolę w karcynogenezie i jest stałym objawem patomorfologicznym szpiczaka mnogiego. W leczeniu szpiczaka znajdują więc zastosowanie leki o działaniu antyangiogennym. Także przeciwciała monoklonalne są istotnym elementem terapii. W ostatnich latach obserwuje się ogromne zainteresowanie terapią antyangiogenną. W badaniach klinicznych różnych faz znajduje się bardzo dużo nowych cząsteczek ukierunkowanych na hamowanie angiogenezy. Wiele wskazuje na to, ze terapia antyangiogenna w przyszłości przyczyni się do poprawy wyników leczenia nowotworów, w tym szpiczaka mnogiego.Angiogenesis plays a key role in carcinogenesis and it is a stabile pathomorphologic symptom of plasmocytoma. Consequently antiangogenic agents are succesfully introduced to plasmocytoma therapy as well as monoclonal antibodies. Recently a great interest has been observed in antiangiogenic therapy. In clinical studies of various phase there are many molecules targeted on angiogenesis inhibition. Numerous facts indicate that antiangiogenic therapy will improve cancer treatment outcomes in future

Postępy w diagnostyce i leczeniu szpiczaka plazmocytowego

Plasmocytoma (multiple myeloma) is characterised by monoclonal proliferation of plasma cells which are producing monoclonal immunoglobulin (M protein). Plasma cell tumor occurrence gives it the second place among hematological tumors. The disease develops in many stages. In the first stage the cells B becomes immortal due to chromosomes translocation in the immunoglobuline heavy chain locus. The time from the first incident to symptomatic disease lasts long and takes 20-30 years, so the average age of multiple myeloma detection is 65. The most important risk factors are the levels of beta2 microglobulines and albumines, on which the prognostic classification is based.Szpiczak plazmocytowy jest wieloetapowo przebiegającą chorobą cechującą się rozrostem monoklonalnych plazmocytów. Celem przedstawionej pracy jest przegląd najnowszych trendów w jego leczeniu. Autorzy przedstawili osiągnięcia terapeutyczne związane z zastosowaniem autologicznego przeszczepu komórek macierzystych, następowej chemioterapii oraz nowych leków o wielokierunkowym działaniu wpływających na procesy apoptozy i angiogenezy, takich jak talidomid i jego analogi oraz inhibitor proteasomu, bortezomib w świetle najnowszych badań klinicznych

Leki immunomodulujące – przełom w leczeniu nowotworów hematologicznych

Introduction of new drugs into therapy of multiple myeloma prolonged significantly progression free survival and overall survival of patients. Taking into account pleiotropic effects of these drugs it was shown that immunomodulatory drugs are very effective in other haematological malignancies such as lymphomas, myelodysplastic syndromes, leukemias or chronic myeloproliferative diseases

Treatment of patients with multiple myeloma not candidates to autologous stem cell transplantation (autoSCT)

Multiple myeloma is still incurable disease, despite significant advances made in therapy during last 10–14 years. The improvement of survival rate is mainly observed in younger patients but not in older. Thus the major problem is to improve survival of older patients

Imatinib therapy of Ph positive acute lymphoblastic leukaemia – 2 case reports

AimThe aim of this works is the presentation of two cases of relapsed Ph positive acute lymphoblastic leukaemia (ALL) to which the tyrosine inhibitor Imatinib (Glivec, Novartis) was applied. This therapy was earlier shown to be very helpful in the treatment of chronic myeloid leukemia.Case discriptionCase 1: A 17 year old patient with Ph positive T-ALL relapsed after allogenic transplantation of marrow and was treated with Imatinib in escalating doses from 200 to 600 mg per day. After 4 weeks of treatment the blastosis in the marrow had fallen from 96% to 7%. Blasts disappeared from the cerebrospinal fluid. At the same time, progression of hepatic and renal failure related to GVHD was observed. Imatinib withdrawal resulted in relapse, uncontrolled proliferation and the death of the patient.ResultsCase 2: Imatinib was used in the case of a 45 year old patient with Ph positive null-ALL and a mediastinal tumour. After autologous bone marrow transplantation, Imatinib therapy was begun for maintenance.. Daily doses of the drug amounted to only 200 mg owing to associated gastric complaints. After two months of therapy, an increase in blast cells in the bone marrow to 18% was noted. FLAM chemotherapy was given and complete haematological remission was achieved.ConclusionsThe cases described illustrate new possibilities in the treatment of Ph positive ALL. It is necessary, however, to conduct clinical trials in larger group of patients for the purposes of establishing optimal dosing, the most suitable phase of the disease in which to begin therapy and possible combinations with chemotherapy

Rola PF4 (chemokiny CXCL4) w powstawaniu skrzepu

Platelet factor 4 (PF4) is released from platelet α granules during activation process. It takes part in clot formation. Physiological concentration of PF4 is essential not only for thrombus formation but also for the anticoagulant potency of heparin. This review is based on experiments performed by one of coauthors.Czynnik płytkowy 4 (PF4) uwalniany jest z ziarnistości α krwinek plytkowych podczas ich aktywacji. Uczestniczy w powstawaniu skrzepu. Prawidłowe stężenie PF4 warunkuje nie tylko efektywność procesów krzepnięcia krwi, ale również skuteczność terapeutycznych dawek heparyny. Praca niniejsza opiera się w dużej mierze na pracach doświadczalnych jednej z współautorek

The activity of human telomerase in the cells of acute leukaemias

Telomeres are the end fragments of chromosomes formed by a number of non-coding double-stranded TTAGGG repeats in vertebrates. During cell division the number of repeats decreases, leading to cell senescence or apoptosis. In immortal cells, including cancer cells, the telomere length is stable and maintained by, among other factors, telomerase. The aim of the study is to compare telomerase activity in normal lymphocytes and in leukaemic cells. Samples of acute leukaemia cells, HL 60 cell line and the lymphocytes of healthy volunteers were examined. Telomerase analysis was performed using TeloTAGGG Telomerase PCR ELISAplus (Roche). The relative telomerase activities (RTA) in leukaemic and normal cells were analysed. A high level of RTA was observed in leukaemic cells

Alterations in TP53, cyclin D2, c-Myc, p21WAF1/CIP1 and p27KIP1 expression associated with progression in B-CLL.

B-cell chronic lymphocytic leukaemia (B-CLL) originates from B lymphocytes that may differ in the activation level, maturation state or cellular subgroups in peripheral blood. Tumour progression in CLL B cells seems to result in gradual accumulation of the clone of resting B lymphocytes in the early phases (G0/G1) of the cell cycle. The G1 phase is impaired in B-CLL. We investigated the gene expression of five key cell cycle regulators: TP 53, c-Myc, cyclin D2, p21WAF1/CIP1 and p27KIP1, which primarily regulate the G1 phase of the cell cycle, or S-phase entry and ultimately control the proliferation and cell growth as well as their role in B-CLL progression. The study was conducted in peripheral blood CLL lymphocytes of 40 previously untreated patients. Statistical analysis of correlations of TP53, cyclin D2, c-Myc, p21WAF1/CIP1 and p27KIP1 expressions in B-CLL patients with different Rai stages demonstrated that the progression of disease was accompanied by increases in p53, cyclin D2 and c-Myc mRNA expression. The expression of p27KIP1 was nearly statistically significant whereas that of p21 WAF1/CIP1 showed no such correlation. Moreover, high expression levels of TP53 and c-Myc genes were found to be closely associated with more aggressive forms of the disease requiring earlier therapy