RAEB II type of myelodysplastic syndrome associated with axillary abscesses - Case Report.

Myelodysplastic syndromes (MDS) are clonal haematopoetic stem cells disorders, characterized by bone marrow dysplasia, ineffecitive haematopoesis and cytopenias. Due to neutropenia, infections are common. A case is presented of a patient with high-risk myelodysplastic syndrome (MDS) complicated by hidradenitis suppurativa that developed in both axillae. Abscesses required multiple incisions and drainage. After five cycles of treatment with azacitidine, the patient underwent allogenic bone marrow transplantation. Unfortunately, six months after the procedure, the patient lost post-transplant chimerism.Treatment with azacitidine was re-started. After the subsequent ten months, blast transformation was observed. Skin lesions in the course of hidradenitis suppurative persisted and were still considerably active.

Safety and Efficacy of Bendamustine Monotherapy in the First-Line Treatment of Patients with Chronic Lymphocytic Leukemia: Polish Lymphoma Research Group Real-Life Analysis.

Bendamustine is a cytostatic drug with a unique structure, combining the features of purine nucleoside analogs and alkylating agents. In patients with chronic lymphocytic leukemia (CLL) it is commonly used in combination with rituximab (BR protocol) both in the first-line as well as subsequent lines of therapy, and in clinical trials it is often combined with new targeted therapies. Therefore, the data on its real-life safety and efficacy are of clinical significance. As the Polish Lymphoma Research Group (PLRG), we retrospectively analyzed the efficacy and tolerability of bendamustine monotherapy in 96 patients with CLL. The median number of bendamustine cycles was 5, and 44 patients did not complete the planned 6 cycles (46%). Among the adverse events associated with the earlier termination of bendamustine treatment, infections were the most common (20.5%), followed by neutropenia (15.9%) and thrombocytopenia (15.9%). Dose reductions and/or delays occurred in 31% of treatment cycles (132 of 425) with neutropenia (17.9%) as the most frequent cause. Efficacy analysis showed an overall response rate of 88.2% with complete remission and partial remission achieved in 43.8 and 41.7% of patients, respectively. At the 24th month of follow-up, progression-free survival was 52% and overall survival was 69.7%. Bendamustine in monotherapy was found to be safe and efficacious, at least in terms of early response. Special attention should be paid to infectious complications, and especially that immune disorders are characteristic in the clinical course of CLL. Our observations suggest efforts must be made to ensure the proper timing and proper dose in the administration of the drug, and to avoid the premature termination of the treatment.

Are myelodysplastic syndromes underdiagnosed in Poland? A report by the Polish Adult Leukaemia Group.

OBJECTIVES: The epidemiology of myelodysplastic syndromes (MDS) differs among countries. Here, we present the first epidemiological indices determined for Poland. METHODS: Twenty-one haematological centres participated in the study. Patients diagnosed with MDS and acute myeloid leukaemia (AML) with 20-29% blasts were enrolled. Data collection was conducted for strictly predefined period. RESULTS: The overall crude incidence rate for all MDS subtypes was 1.95 (95% CI, 1.81-2.09) per 100 000 person-years: 2.46 (95% CI, 2.24-2.69) for males and 1.47 (95% CI, 1.31-1.65) for females; after excluding AML cases, the indices were as follows: 2.35 (95% CI, 2.08-2.66) for males and 1.27 (95% CI, 1.08-1.5) for females. Prevalence rate was 6.2 per 100 000 persons (95% CI, 5.96-6.45), that is 6.86 (95% CI, 6.49-7.24) for males and 5.58 (95% CI, 5.26-5.92) for females. Both incidence and prevalence increased with increasing age. The most frequently diagnosed MDS subtype was refractory cytopenia with multilineage dysplasia (RCMD), responsible for 30.3% of all newly diagnosed MDSs. CONCLUSIONS: RCMD is the most frequent MDS subtype in Poland. Incidence and prevalence indices are lower than those reported for other populations, which probably results from inadequate diagnosis of potential cases of this disease.

New prognostic biomarkers in multiple myeloma.

Multiple myeloma is a malignant neoplastic disease, characterized by uncontrolled proliferation and accumulation of plasma cells in the bone marrow, which is usually connected with production of a monoclonal protein. It is the second most common hematologic malignancy. It constitutes approximately 1% of all cancers and 10% of hematological malignancies. Despite the huge progress that has been made in the treatment of multiple myeloma in the past 30 years including the introduction of new immunomodulatory drugs and proteasome inhibitors, it is still an incurable disease. According to current data, the five-year survival rate is 45%. Multiple myeloma is a very heterogeneous disease with a very diverse clinical course, which is expressed by differences in effectiveness of therapeutic strategies and ability to develop chemoresistance. This diversity implies the need to define risk stratification factors that would help to create personalized and optimized therapy and thereby improve treatment outcomes. Prognostic markers that aim to objectively evaluate the risk of a poor outcome, relapse and the patient's overall outcome are useful for this purpose. The existing, widely used prognostic classifications, such as the Salmon-Durie classification or ISS, do not allow for individualization of treatment. As a result of the development of diagnostic techniques, especially cytogenetics and molecular biology, we were able to discover a lot of new, more sensitive and specific prognostic factors. The paper presents recent reports on the role of molecular, cytogenetic and biochemical alterations in pathogenesis and prognosis of the disease.

Case-adjusted bortezomib-based strategy in routine therapy of relapsed/refractory multiple myeloma shown to be highly effective--a report by Polish Myeloma Study Group.

The observational study was aimed at evaluating response, survival and toxicity of bortezomib-based, case-adjusted regimens in real-life therapy of 708 relapsed/refractory MM patients. Bortezomib was combined with anthracyclines, steroids, thalidomide, alkylators or given in monotherapy. The ORR was 67.9% for refractory and 69.9% for relapsed MM. The median PFS was 14 months and OS 57 months. Patients responding to the therapy had the probability of a 4-year OS at 67.0%. No toxicity was noted in 33.1% of patients. Severe events (grade 3/4) were reported in 35.9% of patients: neurotoxicity (16.7%), neutropenia (9.2%), thrombocytopenia (8.5%), and infections (6.5%). Bortezomib-based, case-adjusted regimens are in real-life practice effective in salvage therapy offering reliable survival with acceptable toxicity for relapsed/refractory MM patients.

Stimulation of erythropoiesis by thalidomide in multiple myeloma patients: its influence on FasL, TRAIL and their receptors on erythroblasts.

The expression of proteins of the tumor necrosis factor (TNF) family on erythroblasts was measured during thalidomide treatment in 29 patients with multiple myeloma (MM). A clinical response was observed in 17 patients (58.6%) and haemoglobin concentration increased in 22 patients (75.9%). The expression of FasL, Fas, TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL-R1 on erythroblasts decreased significantly during thalidomide treatment. Additional in vitro studies revealed that the apoptosis of erythroblasts and the expression of FasL, TRAIL, TRAIL-R1 and TRAIL-R2 was lower in cultures with thalidomide than in control cultures. Altogether our results suggest that thalidomide may stimulate erythropoiesis in MM patients by decreasing the expression of TNF-like ligands/receptors on erythroblasts.

Influence of lovastatin on BCL-2 and BAX expression by plasma cells and T lymphocytes in short-term cultures of multiple myeloma bone marrow mononuclear cells.

Lovastatin (LOV), until now largely used for the treatment of hypercholesterolemia is a new promising drug in multiple myeloma (MM), however, the precise mechanism of its antitumor activity is not clear yet. It is probable that this effect is mediated by down-regulation of BCL-2 expression. In this study, we analyzed BCL-2 and BAX expression in cells of MM patients exposed to LOV in short-term culture. The obtained results indicate an increase in susceptibility to apoptosis both in CD138+ malignant cells and CD8+ T lymphocytes. Interestingly, such a tendency was confirmed in vivo in MM patient subjected to 3 cycles of LOV therapy.

[Hemostatic and fibrinolysis markers in the early phase of acute ischaemic stroke]. / Markery aktywacji wczesnej fazy krzepniecia i fibrynolizy u chorych z zawalem mózgu w najwczesniejszym okresie choroby.

Stroke is the most frequent cause of focal brain damage. It seems that some coagulation and fibrinolysis abnormalities play an important role in this disease. We measured coagulation parameters in 39 patients with acute ischaemic stroke within 1 week of onset of the stroke (1st, 3rd and 7th day), including thrombin-antithrombin complex (TAT), prothrombin fragment F1+2 (F1+2), fibrin degradation products (D-dimer) and fibrinogen (FBG). Marker levels in stroke were compared with controls (n=25). A significant elevation of plasma concentration of TAT, F1+2 and fibrinogen was observed in all days of measurements (p < 0.001). D-dimer level was significantly elevated in 30.7% of patients at the 1st day and in 23.0% of patients at the 3rd day of stroke onset. Marker utility in acute stroke awaits a larger study.

Production of proangiogenic cytokines during thalidomide treatment of multiple myeloma.

Recently a growing number of studies have suggested the efficacy of thalidomide (THAL) in the treatment of relapsed or resistant multiple myeloma. Some of these studies indicate that the thalidomide antimyeloma effect is associated with decreased vessel density. Here we first present our experience with THAL treatment and then focus on the determination of the role of proangiogenic cytokines during THAL therapy. Thirty relapsing or resistant multiple myeloma (MM) patients were treated with THAL at a median dose of 400 mg/daily. Eighteen responded to THAL therapy and 12 were resistant or intolerant to THAL. We determined the plasma level of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) as the main biological parameters associated with tumour angiogenesis. In addition I1-6 and TNFalpha levels were also assayed. Assessment of peripheral blood (PB) and bone marrow (BM) cytokine levels were done before and during THAL treatment at weeks 4 and 8 of therapy. In the responder group VEGF, bFGF I1-6 and TNFalpha concentrations were significantly decreased after four weeks of therapy both in PB and BM. In the non-responder group no significant changes in bFGF and VEGF levels were observed. However, a significant increase in IL-6 and TNF concentrations was evident. We conclude that the significant decrease of VEGF, bFGF, I1-6 and TNFalpha concentrations reflected response to THAL therapy. Also it seems that VEGF is a better marker of response to treatment than bFGF.