Biomedical subjects

Lech Konopka

Publications and source records attributed to Lech Konopka.

7 recordsLinked to original sources

PubMed2007

Cladribine in a weekly versus daily schedule for untreated active hairy cell leukemia: final report from the Polish Adult Leukemia Group (PALG) of a prospective, randomized, multicenter trial.

Cladribine (2-chlorodeoxyadenosine, 2-CdA) treatment-associated infections may shorten potentially long-term survival in hairy cell leukemia (HCL). In search of the optimal mode of 2-CdA administration, 132 patients with untreated HCL were randomized to receive either standard 5-day 2-CdA protocol or a novel schedule of 6 weekly 2-CdA infusions suggested to be less toxic. Analysis of treatment response confirmed similar complete remission rates, overall response rates, progression-free survival, and overall survival in both 2-CdA protocols. However, we did not observe lower toxicity in the weekly schedule. Of special interest, no significant differences were found in the rate of grade 3/4 infections (18% for daily and 26% for weekly protocol, difference -8.2%; 95% confidence interval [CI] -23.2% to 6.9%; P = .28) and the rate of septic deaths (3% for daily and 2% for weekly protocol, difference 1.4%; 95% CI -4.3% to 7.0%; P = .64). In conclusion, HCL treatment with weekly 2-CdA infusions is equally effective but no safer than the standard 5-day 2-CdA protocol.

Adult↗

PubMed2006

Cladribine alone and in combination with cyclophosphamide or cyclophosphamide plus mitoxantrone in the treatment of progressive chronic lymphocytic leukemia: report of a prospective, multicenter, randomized trial of the Polish Adult Leukemia Group (PALG CLL2).

In this prospective randomized trial, we compared the efficacy and toxicity of cladribine (2-CdA) alone to 2-CdA combined with cyclophosphamide (CC) or cyclophosphamide and mitoxantrone (CMC) in untreated progressive chronic lymphocytic leukemia (CLL). Study end points were complete response (CR), overall response, minimal residual disease (MRD), progression-free survival, overall survival, and toxicity. From January 1, 1998 to December 31, 2003, 508 patients from 15 hematology departments were randomized. Compared with 2-CdA, CMC induced higher CR rate (36% vs 21%, P = .004), and a trend for higher CR rate with CC was observed (29% vs 21%, P = .08). Furthermore, the percentage of patients who were in CR and were MRD negative was higher in CMC compared with 2-CdA (23% vs 14%, P = .042). There were no differences in overall response, progression-free survival, and overall survival among treatment groups. Grade 3/4 neutropenia occurred more frequently in CC (32%) and CMC (38%) than in 2-CdA (20%) (P = .01 and P = .004, respectively). Infections were more frequent in CMC compared with 2-CdA (40% vs 27%, P = .02). In conclusion, CMC used in first-line treatment of CLL results in a higher CR rate and suppresses MRD more efficiently than 2-CdA monotherapy, although associates with increased toxicity. No important differences in efficacy and toxicity were found between CC and 2-CdA regimens.

Adult↗

PubMed2006

Transformation in lymphomas--morphological, immunophenotypic and molecular features.

During the course of lymphoma, a clinically more aggressive process with different morphology may develop, referred to as lymphoma transformation. Clonal relationship and pathogenic mechanism of this process are widely debated. The aim of the study was to evaluate morphology, immunophenotype (including EBV status) and clonal relationship in nine cases of lymphoma transformation. Among the six patients with low grade B-cell lymphomas three transformed into high grade B-cell lymphomas (two into diffuse large B-cell lymphoma, one into Burkitt lymphoma) and three into Hodgkin lymphoma. Three other patients with Hodgkin lymphoma presented with transformation into diffuse large B-cell lymphoma in two patients and peripheral T-cell lymphoma in one patient. In all cases there was a sudden clinical change as well as change in morphology and phenotype. In five of the nine patients studied EBV-LMP1 was demonstrated by immunohistochemistry in large transformed lymphoma cells. In two cases molecular studies revealed a different pattern of immunoglobulin gene rearrangement in the large transformed cells as compared to the small cells of primary indolent lymphoma. Thus, they represented secondary, arising de novo neoplasm.

Adult↗

PubMed2005

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).

BACKGROUND: 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. MATERIAL/METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Aged↗

PubMed2002

Enrichment of normal progenitors in counter-flow centrifugal elutriation (CCE) fractions of fresh chronic myeloid leukemia leukapheresis products.

OBJECTIVES: The aim of this study was to assess the suitability of a technique based on counter-flow centrifugal elutriation (CCE), which should allow one to enrich chronic myeloid leukemia (CML) patients' unstimulated native leukapheresis product (nLP) in CD34+ HLADR- cells and BCR-ABL negative cells. METHODS: Six newly diagnosed CML patients were subjected to leukapheresis, and the products were subfractionated with the use of CCE. nLP and all fractions were studied for the presence of CD34+ cells and a proportion of BCR-ABL fluorescence in situ hybridization (FISH)+ cells. RESULTS: CCE fractions with a high flow rate contained the highest proportion of CD34+ cells [mean (SEM) 6.89% (3.88)]. However, CD34+ cells present in low-rate CCE fractions showed a higher proportion of HLADR-[49.6% (13.5 in 70 mL min-1) and 21.5% (11.6 in 110 mL min-1)] than those in 170 mL min-1[3.2% (2.5)] and "rotor off" [3.4% (1.9)]. This was associated with lower proportions of BCR-ABL FISH+[8.1% (4.8) and 1.9 (1.7)] and smaller BCR-ABL to ABL transcript ratios [0.58 (17) and 0.26 (0.08) in 70 and 110 mL min-1] fractions as compared to 140 and 170 mL min-1 fractions [21.6% (5.2) and 31.6% (15.3) for BCR-ABL FISH+ cells and 0.75 (0.16) and 0.90 (0.24) for BCR-ABL/ABL]. Fractions with the lowest proportions of BCR-ABL-positive cells and the lowest BCR-ABL/ABL transcript ratios (110 mL min-1) contained from 1.3 x 106 to 82.7 x 106 (median: 3.97 x 106) CD34+ cells. CONCLUSIONS: In the present study we have shown that CCE may be used effectively to obtain nLP fractions enriched in normal hematopoietic progenitors.

Adult↗

PubMed2002

Re-treatment with cladribine-based regimens in relapsed patients with B-cell chronic lymphocytic leukemia. Efficacy and toxicity in comparison with previous treatment.

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.

Adult↗

PubMed2002

G-CSF administered in time-sequenced setting during remission induction and consolidation therapy of adult acute lymphoblastic leukemia has beneficial influence on early recovery and possibly improves long-term outcome: a randomized multicenter study.

Sixty-four untreated adult acute lymphoblastic leukemia (ALL) patients were randomized to receive chemotherapy alone, n = 31 or chemotherapy and granulocyte colony stimulating factor (G-CSF), n = 33. During induction patients received G-CSF for 5 days between four weekly Epirubicin+Vcr administrations, starting 36 h after each application and finishing 48 h before the next one with the intention to possibly generate a cell cycle dependent protection of normal hematopoietic progenitors and to stimulate granulopoiesis. The complete remission (CR) rate equaled 94% in the G-CSF group and 87% in controls. Patients who received G-CSF, if compared to the controls, had shorter granulocytopenia during induction and consolidation, displayed a lower infection rate, completed the induction-consolidation quicker and stayed shorter in hospital during induction, p < 0.001-0.04. Follow-up at 2 years revealed a rather higher probability of survival (59 vs. 27%, p = 0.04) and a lower relapse rate (32 vs. 60%) in G-CSF arm than in controls. The beneficial influence of G-CSF administered in time-sequenced fashion on survival needs further confirmation.

Adolescent↗