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The aim of this study was to assess the prognostic value of pretreatment clinical and laboratory parameters in refractory or relapsed multiple myeloma (MM) patients who have a long-term response to thalidomide (THAL), lasting at least 18 months. The study was carried out on 234 patients who received THAL for relapsed/refractory myeloma. Out of the 234 patients, 129 patients (55.1%) responded to THAL with a mean response duration of 11.9 months (ranging from 1 to 48) and an overall survival rate of 20.3 months (ranging 1-55 months). In 64 patients (27.4% of the whole group), the response to THAL lasted > or =18 months with a mean response lasting 24 months. Statistical analysis of the group of nonresponders and patients with long-term response to THAL showed a significantly higher serum albumin level (P=0.0003) and haemoglobin level (P=0.05), as well as a lower beta2 microglobulin (beta2M) (P=0.022), LDH (P=0.045) serum level in patients with long-term response. In this study, the LDH and serum albumin level were predictors for response to THAL therapy. The beta2M serum level was not a predictor for response to THAL. The albumin serum level was the best parameter distinguishing the group of patients with long-term response to THAL from the entire responding group (P=0.02). [ABSTRACT FROM AUTHOR]

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., (© 2019 S. Karger AG, Basel.)

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., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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.

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.

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.

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.

Supernatants from short-term culture of peripheral blood and bone marrow mononuclear cells obtained from 22 multiple myeloma patients were used to measure the concentration of TNF-alpha, HGF, IL-6 and its soluble receptor (sIL-6R), VEGF and bFGF. Cells were cultured with or without thalidomide (THAL). We observed statistically significant decrease in TNF-alpha, HGF, IL-6, sIL-6R in supernatants from THAL cultures compared to cells cultured without THAL. Flow cytometry technique was applied to study the Bcl2 expression on CD 4, CD 8 and CD 138 positive cells. The statistically significant decrease in Bcl2 expression on myeloma cells (CD 138+) was observed both in PB and BM cultures. THAL could inhibit the plasma cell growth both by diminishing proangiogenic cytokines production and enhancing myeloma cell apoptosis.

Thalidomide, a derivative of alpha-N-phthalimidoglutarimide acid, was withdrawn from the market in the 1960s because of severe birth defects. Recent reports have suggested antiangiogenic and antitumor activity of this drug. We have treated 52 patients with refractory multiple myeloma at age from 32 to 79 years (mean 63) with thalidomide at a dose of 200-400 mg daily. Out of the group of 52 patients, 27 patients (52%) responded to the therapy, in 25 patients (48%) a response was not achieved (decline in monoclonal protein was smaller than 25%). There was a systematic improvement in haemoglobin concentration, erythrocyte count and thrombocyte count during thalidomide therapy. Leukocyte count showed an inclination to decrease, however observed changes were not statistically significant. The improvement in morphotic parameters of blood was observed both in responder and nonresponder patients.

Background and Objectives: Thalidomide is currently used as a very promising drug in patients with recurrent multiple myeloma or those refractory to chemotherapy. Literature data show prolonged survival in patients with advanced multiple myeloma treated with thalidomide but the optimal time and dose of thalidomide treatment remain to be established., Design and Methods: We have treated 53 refractory or relapsed myeloma patients with thalidomide (Grunenthal, Aachen). The patients received thalidomide orally as monotherapy at a starting dose of 200 mg daily, with a dose increase of 100 mg every week to a maximum well-tolerated dose of 400 mg. All the patients qualified for the therapy underwent clinical and laboratory assessments every 4 weeks. Laboratory tests included complete blood count, electrophoresis, immunoglobulin level, lactate dehydrogenase (LDH), C-reactive protein, b2 microglobulin concentration, liver and renal function tests and there was also a monthly neurological examination. Bone marrow aspiration was performed every 3 months during the 12-month treatment., Results: Among 53 evaluable patients, a clinical response was observed in 27 (51%): there was a major response in 7 patients, a partial response in 12 and a minor response in 8., Interpretation and Conclusions: In responding patients the earliest response was observed after 4 weeks of treatment and the latest after 12 weeks of treatment. Our results, obtained during a long observation period, show that thalidomide is an effective drug, with an acceptable degree of toxicity, in patients with refractory multiple myeloma.

An important role in the formation of haemostasis defects in haemodialysed patients play phospholipids. The disturbances of platelet activity play an essential part in platelet structure and function. In uraemic patients changed plasma lipid pattern is observed, as well as positive influence of human recombinant erythropoietin (rhuEPO) on some plasma lipid disorders in these patients. The aim of this study was to investigate rhuEPO influence on platelet phospholipid composition in haemodialysed patients. RhuEPO was applied subcutaneously, 2000j twice a week. Before rhuEPO treatment significant decrease of phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylcholine (PC) contents was observed, as compared with control group. After rhuEPO treatment a significant increase of PE and PC contents was noted. The obtained results suggest that rhuEPO partially normalizes changed platelet phospholipids composition, but detailed mechanism of this influence is unclear.