Publications (12)27.96 Total impact
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Article: Prognostic value of the bone marrow microvessel density in progressive B-cell chronic lymphocytic leukemia.
Leukemia & lymphoma 07/2010; 51(7):1351-3. · 2.40 Impact Factor -
Article: Influence of cladribine alone and in combination with cyclophosphamide or cyclophosphamide and mitoxantrone on bone marrow angiogenesis in chronic lymphocytic leukemia.
Leukemia and Lymphoma 06/2007; 48(5):1042-4. · 2.58 Impact Factor -
Article: [Tyrosine kinase inhibitors in the therapy of chronic myeloid leukaemia].
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ABSTRACT: Chronic myeloid leukemia (CML) is a malignant clonal disorder of hematopoietic stem cells resulting in increased myeloid and erythroid cells and platelets, and marked hyperplasia in the bone marrow. The natural history of CML is progression from a benign chronic phase, often through an accelerated phase, to a rapidly fatal blast crisis within 3-5 years. The constitutively activated ABL tyrosine kinase domain of the chimeric BCR-ABL oncoprotein is responsible for the transformation of hematopoietic stem cells and the symptoms of CML. Imatinib mesylate (Glivec), a specific small-molecule inhibitor of BCR-ABL, has become the standard drug therapy in all phases of the disease. Imatinib has greatly improved the outcome for patients with CML. Unfortunately, mutations causing resistance to imatinib are leading to relapse in some patients. Considerable progress has recently been made in understanding the structural biology of ABL and the molecular basis for resistance, facilitating the discovery and development of second- generation drugs designed to combat mutant forms of BCR-ABL. The first of these compounds to enter clinical development were dasatinib (BMS-354825) and AMN107 and, from phase I results, both of these promise a breakthrough in the treatment of imatinib-resistant CML.Postępy Higieny i Medycyny Doświadczalnej (Advances in Hygiene and Experimental Medicine) 02/2006; 60:490-7. -
Article: Comparison of cladribine plus prednisone with chlorambucil plus prednisone in patients with chronic lymphocytic leukemia. Final report of the Polish Adult Leukemia Group (PALG CLL1).
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ABSTRACT: We previously published an early report of a randomized, multicenter trial on the efficacy and toxicity of cladribine (2-CdA) + prednisone (P) compared with chlorambucil (Chl) + P in previously untreated patients with progressive or symptomatic chronic lymphocytic leukemia. Here we present the final report of this study. Of 229 patients, 126 received 2-CdA+P and 103 Chl+P. Patients with no response or progression after three courses or who relapsed earlier than 12 months after completing one treatment were switched to the other. Patients who relapsed later were retreated with the same schedule as before. Thirty-three patients were retreated with 2-CdA+P and 19 with Chl+P. Overall response (and complete response) rates were 35% (6%) and 47% (16%), respectively. In 50 patients initially treated with Chl+P and then with 2-CdA+P, complete response (CR) was achieved in 12 (24%) and overall response (OR) in 32 (64%). In 28 patients originally treated with 2-CdA+P and then with Chl+P, CR in 1 (3%, p=0.01) and OR in 6 (21%, p=0.003) were obtained. We found no statistically significant difference in overall survival time in patients treated initially with 2-CdA+P and Chl+P aged 60 years (4.63 and 5.27 years, respectively, p=0.45), 60-70 years (3.29 and 3.14 years, p=0.79), and >70 years (1.53 and 1.93 years, p=0.11). 2-CdA+P is significantly more effective as a second-line treatment and re-treatment than Chl+P. However, we found a trend to longer survival in elderly patients treated with Chl+P.Medical science monitor: international medical journal of experimental and clinical research 10/2005; 11(10):PI71-9. · 1.70 Impact Factor -
Article: The effect of subsequent therapies in patients with chronic lymphocytic leukemia previously treated with prednisone and either cladribine or chlorambucil.
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ABSTRACT: We present the long-term follow-up and results of subsequent treatments in patients with chronic lymphocytic leukemia treated initially with cladribine + prednisone or chlorambucil + prednisone in a randomized, cross-over study. We found higher complete and overall responses rates in patients who received cladribine + prednisone as first and second-line treatment but no significant differences in survival.Haematologica 08/2005; 90(7):994-6. · 6.42 Impact Factor -
Article: Richter's syndrome in the brain first manifested as an ischaemic stroke.
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ABSTRACT: Isolated central nervous system involvement in Richter's syndrome (RS) is extremely rare and only 6 such cases have been described, so far. We report a 60-year-old woman with B-cell chronic lymphocytic leukemia (B-CLL) heavily pretreated with cladribine based regimens and rituximab in whom RS in the brain was first manifested as a stroke. Initial cranial computed tomography (CT) revealed a hypodense area in the right parietal lobe showing no contrast enhancement. The follow-up CT done after 2 months showed an irregular, slightly hyperdense tumor surrounded by oedema with mass effect and midline shift. However, cerebrospinal fluid (CSF) examinations revealed no pathological changes. Neurosurgical operation was performed and the diagnosis of diffuse large B-cell lymphoma (DLBCL) has been established on the basis of histological and immunological investigation of the tumor. The pattern of immunoglobulin heavy chain (IgH) gene rearrangement in the patients' bone marrow aspirate and brain tumor was identical and suggested that both tumors originated from the same B-cell progenitors. The patient was then treated with brain irradiation (2000 cGy) and complete remission as assessed by MRI was achieved. Significant neurological improvement was observed and no clinical progression was stated 3 months after radiotherapy.Leukemia and Lymphoma 07/2004; 45(6):1261-7. · 2.58 Impact Factor -
Article: Coexistence of chronic lymphocytic leukemia and essential thrombocythemia.
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ABSTRACT: The association of chronic lymphocytic leukemia (CLL) with essential thrombocythemia (ET) is an extremely rare event and until now 3 patients with such coexistence have been reported in the literature. We report a 77-year-old white woman in whom these two disorders were diagnosed concomitantly on the basis of peripheral blood count and cytology, bone marrow cytology and histology, immunophenotyping, as well as exclusion criteria. The diagnosis of ET was also supported by spontaneous in-vitro erythroid colony growth and by evaluation of thrombopoietin (TPO) serum level. Interphase FISH analysis allowed to detect 13q14.3 deletion in 98% of lymphocytes nuclei. In contrast this aberration was not observed in the megakaryocytes. The results of PCR analysis of IgG gene rearrangement showed distinct bands characteristic for monoclonal lymphoid population in bone marrow, peripheral blood and inguinal lymph node. The patient was started on hydroxyurea 1 g/day and normalization of the platelet count was achieved. Possible etiopathogenic relationships between both disorders and differential diagnosis of ET and reactive thrombocytosis (RT) are discussed.Leukemia and Lymphoma 09/2003; 44(8):1425-31. · 2.58 Impact Factor -
Article: Re‐treatment with cladribine‐based regimens in relapsed patients with B‐cell chronic lymphocytic leukemia
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ABSTRACT: The aim of the study was to determine the effectiveness and toxicity of cladribine (2-CdA) used alone or in combination with prednisone (P) or cyclophosphamide and mitoxantrone in re-treatment of patients with progressive B-cell chronic lymphocytic leukemia (B-CLL). We analyzed treatment outcome in 40 patients who had responded to previous treatment with 2-CdA-based regimens. Criteria for re-treatment were the same as for the first treatment. The patients were retreated with the same agents if they responded to the first treatment and then relapsed with progressive disease not earlier than 3 months after achieving the first response. Eight patients received 2-CdA alone (0.12 mg kg−1 d−1) i.v. for 5 d, and 21 patients additionally were given P (30 mg m−2 d−1) orally, also for 5 d. Eleven patients received 2-CdA for 3 d combined with cyclophosphamide (650 mg m−2) i.v. and mitoxantrone (10 mg m−2) i.v. on day 1 (CMC regimen). The cycles were repeated usually at 4 wk intervals or longer if severe myelosuppression or infections occurred. The therapy was finished if complete remission (CR) was achieved or until maximum of six courses. Overall response (OR) in re-treatment was obtained in 16 out of 40 (40%) patients (95% CI 16–64), including 62% after 2-CdA, 33% after 2-CdA +P and 36% after CMC. CR was obtained in four (10%) patients. Residual disease evaluated in the patients with CR by surface immunophenotyping had been demonstrated in 5 out of 16 (31%) patients after the first treatment and in one out of four (25%) patients after re-treatment. The median progression-free survival (PFS) was 16 months (range 3–39) for the first treatment and 9.5 months (range 3–18) for re-treatment (P=0.34). Grade III or IV neutropenia was observed in 20% patients during the first treatment and in 35% patients during re-treatment (P=0.1). 2-CdA-induced thrombocytopenia occurred in 20% and 42% of the patients, respectively (P=0.05). Anemia was also more frequent during re-treatment (35%) than during the first treatment (7%) (P=0.007). Autoimmune hemolytic anemia developed in four (10%) of the patients during or after re-treatment. Severe infections, including pneumonia and herpes reactivation, occurred in 11 patients during the first treatment and in 10 patients during re-treatment. Twelve (30%) patients died during the study. Infections were the cause of death in six and AIHA in two patients. In conclusion, 2-CdA applied in monotherapy or in combination with prednisone or cyclophosphamide and mitoxantrone has therapeutic activity in some B-CLL patients in whom these drugs induced earlier complete or partial remission. However, since the second response is usually shorter and myelotoxicity more pronounced than during the first therapy, more clinical trials to find other therapeutical approaches are necessary.European Journal Of Haematology 09/2002; 69(1):27 - 36. · 2.61 Impact Factor -
Article: Re-treatment with cladribine-based regimens in relapsed patients with B-cell chronic lymphocytic leukemia. Efficacy and toxicity in comparison with previous treatment.
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ABSTRACT: The aim of the study was to determine the effectiveness and toxicity of cladribine (2-CdA) used alone or in combination with prednisone (P) or cyclophosphamide and mitoxantrone in re-treatment of patients with progressive B-cell chronic lymphocytic leukemia (B-CLL). We analyzed treatment outcome in 40 patients who had responded to previous treatment with 2-CdA-based regimens. Criteria for re-treatment were the same as for the first treatment. The patients were retreated with the same agents if they responded to the first treatment and then relapsed with progressive disease not earlier than 3 months after achieving the first response. Eight patients received 2-CdA alone (0.12 mg kg(-1) d(-1)) i.v. for 5 d, and 21 patients additionally were given P (30 mg m(-2) d(-1)) orally, also for 5 d. Eleven patients received 2-CdA for 3 d combined with cyclophosphamide (650 mg m(-2)) i.v. and mitoxantrone (10 mg m(-2)) i.v. on day 1 (CMC regimen). The cycles were repeated usually at 4 wk intervals or longer if severe myelosuppression or infections occurred. The therapy was finished if complete remission (CR) was achieved or until maximum of six courses. Overall response (OR) in re-treatment was obtained in 16 out of 40 (40%) patients (95% CI 16-64), including 62% after 2-CdA, 33% after 2-CdA +P and 36% after CMC. CR was obtained in four (10%) patients. Residual disease evaluated in the patients with CR by surface immunophenotyping had been demonstrated in 5 out of 16 (31%) patients after the first treatment and in one out of four (25%) patients after re-treatment. The median progression-free survival (PFS) was 16 months (range 3-39) for the first treatment and 9.5 months (range 3-18) for re-treatment (P=0.34). Grade III or IV neutropenia was observed in 20% patients during the first treatment and in 35% patients during re-treatment (P=0.1). 2-CdA-induced thrombocytopenia occurred in 20% and 42% of the patients, respectively (P=0.05). Anemia was also more frequent during re-treatment (35%) than during the first treatment (7%) (P=0.007). Autoimmune hemolytic anemia developed in four (10%) of the patients during or after re-treatment. Severe infections, including pneumonia and herpes reactivation, occurred in 11 patients during the first treatment and in 10 patients during re-treatment. Twelve (30%) patients died during the study. Infections were the cause of death in six and AIHA in two patients. In conclusion, 2-CdA applied in monotherapy or in combination with prednisone or cyclophosphamide and mitoxantrone has therapeutic activity in some B-CLL patients in whom these drugs induced earlier complete or partial remission. However, since the second response is usually shorter and myelotoxicity more pronounced than during the first therapy, more clinical trials to find other therapeutical approaches are necessary.European Journal Of Haematology 08/2002; 69(1):27-36. · 2.61 Impact Factor -
Article: Cladribine combined with cyclophosphamide is highly effective in the treatment of chronic lymphocytic leukemia.
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ABSTRACT: The aim of the study was to evaluate the activity and toxicity of cladribine (2-CdA) in combination with cyclophosphamide (CY), the CC schedule, in patients with previously untreated B-cell chronic lymphocytic leukemia (B-CLL). From November 1998 to May 2002 82 patients with advanced or progressive B-CLL received treatment with 2-CdA at a dose of 0.12 mg/kg for three consecutive days and CY at a dose of 650 mg/m(2) on day 1. The cycles were repeated at four week intervals or longer if severe myelosuppression occurred. Guidelines for the evaluation of response and toxicity were those developed by the National Cancer Institute sponsored Working Group. Minimal residual disease (MRD) was detected by immunophenotyping only in patients with CR by standard criteria. In the analysed group an overall response (OR) rate (CR+PR) of 87.8% (95% CI 80.7-94.9%) was achieved, including complete response (CR) in 29.3% patients (95% CI 19.4-39.1%). Twenty-two of 24 patients with CR and 39 of 48 patients with PR are still in remission. Median duration of follow-up in these patients is 11.8 months (range 3-25.4). MRD was only detected in six out of 24 (25%) patients with CR. Grade III/IV thrombocytopenia was seen in four patients (4.9%) and neutropenia in 10 (12.2%). Severe infections were noted in 21 (25.6%) patients. Thirteen patients died, including seven with treatment related toxicity, one because of CLL progression and five because of reasons not related to CLL. In conclusion, the CC schedule is a highly active regimen in previously untreated B-CLL, with acceptable toxicity. The efficacy of the regimen seems to be higher than observed earlier after treatment with 2-CdA alone. A randomized clinical trial is in progress in our institutions.The Hematology Journal 02/2002; 3(5):244-50. · 1.86 Impact Factor -
Article: Cladribine in combination with mitoxantrone and cyclophosphamide(CMC) in the treatment of heavily pre‐treated patients with advanced indolent lymphoid malignancies
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ABSTRACT: The aim of our study was to determine the effectiveness and toxicity of combined chemotherapy consisting of cladribine (2-chloro-deoxyadenosine, 2-CdA), mitoxantrone and cyclophosphamide (CMC regimen) in the treatment of refractory or relapsed indolent lymphoproliferative disorders. The treatment course consisted of 2-CdA given at a dose of 0.12 mg/kg/24 h in a 2-h intravenous infusion for 5 (CMC5) or 3 (CMC3) consecutive days, mitoxantrone 10 mg/m2 on day 1 and cyclophosphamide 650 mg/m2/iv on day 1. Thirty-three patients (19 with B-CLL and 14 with LG-NHL) entered the study and all of them were eligible. Twenty patients (60.6%) were recurrent after prior therapy and 13 (39.4%) had refractory disease. All patients received 5 or more cycles of chemotherapy before CMC treatment. Twenty-one patients were treated with CMC5 regimen and 12 with CMC3 regimen. The overall response rate, including CR and PR, was 48.6% (95% CI 32–66). There were no differences in the frequency of responses between the CMC3 and CMC5 treated groups (p>0.05). One patient with B-CLL and three patients with lymphocytic lymphoma achieved CR (12.1%). Among 12 patients (36.4%) who achieved PR there were 6 CLL patients, and 6 lymphoma patients. The major toxicity was myelosuppression. Severe neutropenia was seen in 11/33 (33.3%) patients, more frequently in patients who received CMC5 than in the patients who received CMC3, both in the CLL (50.0% and 28.5%, respectively) and in the LG-NHL group (22.2% and 0%, respectively). The rate of thrombocytopenia was similar in both groups. Infections and fever of unknown origin complicated the treatment with CMC5 more often than with CMC3: five episodes were seen in 3 patients treated with CMC3 when compared to 15 episodes in 12 patients treated with CMC5. In conclusion, the CMC programme is an active combined regimen in heavily pre-treated CLL and LG-NHL patients. However, its toxicity is significant and we suggest a shortening of 2-CdA infusion from 5 to 3 d in further studies. Whether a combination of 2-CdA with cyclophosphamide and mitoxantrone would result in improved outcome as compared to 2-CdA alone, is being investigated in a prospective, randomised trial.European Journal Of Haematology 02/2001; 66(3):188 - 194. · 2.61 Impact Factor -
Article: The interaction of 2-chlorodeoxy adenosine (2-CDA) and interferon α (IFN-α) on normal and myeloid leukemia hematopoiesis in vitro
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ABSTRACT: The influence of 2-CDA and interferon α (IFN-α) on the CFU-GM cells from ten normal individuals as well as on the CFU-GM from ten patients with chronic myeloid leukemia (CML) and on clonogenic leukemic blasts (CFU-L) from ten patients with acute myeloid leukemia (AML) in semi-solid cultures in vitro was investigated. The agents were added to the cultures alone and in combinations at concentrations of 20, 40 and 80 nM/I of 2-CDA and 102, 103 and 104U/ml of IFN-α. A dose-dependent growth inhibition of CFU-GM as well as of CFU-L was observed. The inhibitory effect of both drugs used alone was significantly greater on the CFU-GM cells from patients with CML than on cells from normal donors. However, 2-CDA and IFN-α used together showed greater additive effect on the CFU-L than on the CFU-GM from normal donors and from CML patients.Leukemia Research.
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2010
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University of Lodz
Łódź, Lodz Voivodeship, Poland
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