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Biomedical subjects

M Komarnicki

Publications and source records attributed to M Komarnicki.

At least 19 recordsLinked to original sources
PubMed2004

Second malignancies and Richter's syndrome in patients with chronic lymphocytic leukaemia treated with cladribine.

The increased frequency of second malignancies in chronic lymphocytic leukaemia (CLL) is well known. Moreover, antineoplastic therapy additionally increases the risk of secondary cancers. In this study, we analysed whether treatment with cladribine (2-chlorodeoxyadenosine, 2-CdA) during the course of CLL had an impact on the subsequent occurrence of either secondary solid tumours or Richter's syndrome. There were 1487 eligible patients, 251 treated with 2-CdA alone, 913 treated with alkylating agents (AA)-based regimens alone and 323 treated with both 2-CdA and AA. Median time from the start of CLL treatment to the diagnosis of secondary malignancy was 1.9 years (0.5-5.1 years) for the 2-CdA group, 1.8 years (0.3-7.9 years) for the AA group and 3.9 years (0.3-8.4 years) for the 2-CdA+AA group. A total of 68 malignancies were reported in 65 patients. Ten events were non-melanotic skin cancers and were excluded from the analysis, leaving 58 events in 58 patients. In the group of patients treated with 2-CdA alone, there were 15 (6.0%) cases, in the group of patients treated with AA alone there were 26 (2.8%) cases, and in the group treated with 2-CdA+AA there were 17 (5.3%) cases of secondary malignancies. The differences between the frequency of secondary malignancies in the 2-CdA and 2-CdA+AA versus AA alone groups were not significant (P=0.05 and P=0.06, respectively). Only lung cancers occurred significantly more frequently in the 2-CdA (2.8%) and 2-CdA+AA (2.2%) treated groups compared with the AA patients (0.3%) (P<0.001 and P<0.01, respectively). In conclusion, 2-CdA in CLL patients does not seem to increase the risk of secondary malignancies except for lung cancers. However, further studies are necessary to establish the real risk of lung cancer in CLL patients treated with 2-CdA.

Adult↗
PubMed2004

Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study.

To assess the efficacy of an original DAC-7 regimen: daunorubicine (DNR) 60 mg/m2/day, days 1-3; cytarabine (AraC) 200 mg/m2/day, days 1-7; cladribine (2-CdA) 5 mg/m2/day, days 1-5, 400 untreated adult acute myeloid leukemia patients (including 63 with preceding myelodysplastic syndrome), aged 45 (16-60) years were randomized to either DAC-7 (n=200) or DA-7 (without 2-CdA, n=200). The overall CR rate equaled 72% for DAC-7 and 69% for DA-7 arm (P=NS). After a single course of DAC-7 induction, the CR rate equaled 64% and was significantly higher compared to 47% in the DA-7 arm (P=0.0009). Median hospitalization time during the induction was 7 days shorter for DAC-7 compared to the DA-7 group (33 vs 40 days, P=0.002). Toxicity was comparable in both groups. The probability of 3-year leukemia-free survival (LFS) for DAC-7 and DA-7 group equaled 43 and 34%, respectively (P=NS). There was a trend toward higher LFS rate for patients aged >40 years receiving DAC-7 compared with DA-7 regimen (44 vs 28%, P=0.05). This study proves that addition of 2-CdA increases antileukemic potency of DNR+AraC regimen, thus resulting in a higher CR rate after one induction cycle when compared to DA-7, without additional toxicity. It shortens hospitalization time and may improve long-term survival in patients aged >40 years.

Adolescent↗
PubMed2004

Efficacy and safety of fludarabine and cyclophosphamide combined therapy in patients with refractory/recurrent B-cell chronic lymphocytic leukaemia (B-CLL)-Polish multicentre study.

The aim of this study was to investigate the efficacy of a combination of fludarabine (F) and cyclophosphamide (C) in the treatment of patients with refractory/recurrent B-cell chronic lymphocytic leukaemia (B-CLL). Between November 1999 and December 2001, 63 patients with B-CLL (median age 60 years) received a regimen that consisted of F 25 mg/m2 and C 250 mg/m2, days 1-3, intravenously, every 4 weeks, for a maximum of 6 courses, Response and toxicity were assessed according to current criteria (NCI-WG and WHO). Complete and partial remissions were achieved in 17.5% and 55.6% of patients, respectively; 19% of patients had stable disease and 7.9% of patients showed disease progression. The median follow-up was 16.5 (range 1.5-32) months. The median duration of progression-free survival (PFS) has not been reached among patients treated with FC regimen as second-line therapy. The median PFS was 13 (range 8-26) months in the 19 responding patients treated with FC regimen as third-line therapy. The most frequent side-effects were neutropenia (45%), thrombocytopenia (42%) and infections (57%). We conclude that the combination of fludarabine and cyclophosphamide demonstrated significant efficacy in pretreated, advanced B-CLL patients, with tolerable toxicity.

Adult↗
PubMed2002

Ambulatory electrocardiographic evaluation of the heart in patients treated by megachemotherapy and bone marrow transplantation.

The aim of the study was evaluation of the frequency of conduction defects and cardiac arrhythmias before and one month (once a week) after bone marrow transplantation (BMT). It was evaluated by 24-hour electrocardiography based on the Holter's method. There were 50 patients (mean age 29.0 years) examined who were treated with megachemotherapy based on BuCy2, BuCy4 (busulphan and cyclophosphamide), BEAM (carmustine, etoposide, cytarabine, melphalan) and dexaBEAM (dexa-dexamethason) programs before BMT. No heart conduction defects occurred. The mean heart rate increased after BMT. Tachycardia (> 100/min) was observed in 92.5-98.1% of patients and bradycardia (< 60/min) in 41.6-68.0% patients. In 6% of patients bradycardia below 40/min occurred. The heart rate was increased in patients who previously used anthracycline antibiotics, had anaemia or fever, and in patients after autologous BMT (p < 0.05). The complex ventricular extrasystoles were detected in 20% of patients before megachemotherapy. They were more frequently observed in patients with hypokalemia (p < 0.05). After therapy these extrasystoles were observed in a total of 24% patients. There was a statistically significant correlation between this kind of extrasystole and age. The extrasystoles developed mainly in young men. In 10% they occurred de novo and also mainly in men. The heart failure (III degrees, IV degrees according to NYHA) occurred in 14% of patients and death caused by heart (or multiorgan) damage in 18%. Older patients and those who had higher mean heart rate during the first month after BMT were dying more frequently (p < 0.05).

Adolescent↗
PubMed2001

Platelet aggregation and prostaglandin metabolism in uremic patients.

The pathogenesis of depressed platelet activity in uremia is still unknown. The influence of some uremic toxins on platelet aggregation (PLA) and prostaglandin metabolism in 50 uremic patients treated by hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) was studied. Fifty-seven healthy volunteers (HVs) served for reference values. Adenosine diphosphate (ADP) and thrombin (Thr) were used as agonists of PLA. PLA was determined using the Born method. Malonyldialdehyde (MDA) levels in platelets as an indicator of prostaglandin metabolism, after stimulation with arachidonic acid, were measured according to Stuart. The relationship of PLA and prostaglandin metabolism with plasma concentrations of methylguanidine (MG), guanidinosuccinic acid (GSA), and creatinine (Cr) was assessed. PLA-ADP values in regular HD patients (42 +/- 5 mm) were significantly lower than in CAPD patients (65 +/- 8 mm) and HVs (73 +/- 3 mm). PLA-Thr values in HD patients (25 +/- 4 mm) were significantly lower than in CAPD patients (34.9 mm) and HVs (36 +/- 3 mm). MDA levels in HD patients (7 +/- 1 nmol/L/10(9)) were significantly lower than in CAPD patients (12 +/- 2 nmol/L/10(9)) and HVs (15 +/- 1 nmol/L/10(9)). In HD patients, inverse correlations of PLA-ADP with MG levels (r = -0.92), PLA-Thr with Cr levels (r = -89), and MDA levels with GSA levels (r = -0.86) were found. In CAPD patients, no relationship of PLA and MDA with uremic toxins was observed. Depressed activity of platelets and prostaglandin metabolism was strongly expressed in HD patients.

Adenosine Diphosphate↗
PubMed2001

Rituximab (Mabthera, Rituxan) in patients with recurrent indolent lymphoma: evaluation of safety and efficacy in a multicenter study.

The objective of this multiinstitutional study was to evaluate the safety and efficacy of rituximab at standard four weekly doses in patients with recurrent indolent lymphoma. Thirty-eight patients entered into this study, 63% had follicular lymphoma and 61% had an IPI score of 2 or more. Median disease duration was 3 yr, median number of prior treatments was three, and 66% of patients responded to the immediate past treatment with a median remission duration of 3 mo. A total of 158 antibody doses were given, including two patients who received two courses of four infusions each. One patient developed acute respiratory failure after the second dose and required assisted ventilation. There was no immediate relationship to the antibody infusion and no evidence of infection. This complication resolved and the patient successfully completed the full course of the antibody treatment. Another patient discontinued therapy after the second dose owing to intolerable fever and painful erythema. Sixty percent of the first, and 20% of subsequent rituximab infusions were associated with infusion-related reactions including mild fever, chills, and occasional skin eruptions. Complete and partial responses were achieved in 24% and 35% of 34 evaluable patients, respectively, for an overall response rate of 59%. The median time to progression/relapse in responding patients was 16 mo (95% CI, 6.4, 25.6) compared with a median of 3 mo duration of response to the immediate previous therapy in these patients. Longer response duration post rituximab monotherapy than with previous treatment in this series of heavily pretreated patients suggests a major role for the antibody in the therapy of patients with indolent lymphoma.

Adult↗
PubMed2000

Cladribine with or without prednisone in the treatment of previously treated and untreated B-cell chronic lymphocytic leukaemia - updated results of the multicentre study of 378 patients.

Between January 1992 and January 1999, we treated 378 B-chronic lymphocytic leukaemia (CLL) patients with cladribine (2-CdA), and 255 of the patients were also treated with prednisone. A total of 194 patients were previously untreated, and 184 had relapsed or refractory disease after previous other therapy. Complete response (CR) was obtained in 111 (29.4%) and partial response (PR) in 138 (36.5%) patients, giving an overall response (OR) rate of 65.9%. CR and OR were achieved more frequently in patients in whom 2-CdA was a first-line treatment (45.4% and 82.5% respectively) than in the pretreated group (12.5% and 48.4% respectively) (P < 0.0001). The median duration of OR for previously untreated patients was 14.7 months and for pretreated patients 13.5 months (P = 0.09). The median survival evaluated from the beginning of 2-CdA treatment was shorter in the pretreated group (16.3 months) than in the untreated group (19.4 months) (P < 0.0001). A total of 117 (63.9%) patients died in the pretreated group and 63 (32.6%) in the untreated group. In pretreated patients, 2-CdA + prednisone (P) and 2-CdA alone resulted in similar OR (51.0% and 45.0% respectively; P = 0.4). In contrast, in untreated patients, 2-CdA + P produced a higher OR (85.4%) than 2-CdA alone (72.1%) (P = 0.04). Infections and fever of unknown origin, observed in 91 (49.4%) pretreated and 74 (38.1%) untreated patients (P = 0.03), were the most frequent toxic effects. Our results indicate that 2-CdA is an effective, relatively well-tolerated drug, especially in previously untreated CLL.

2-Chloroadenosine↗
PubMed1997

The effect of 2-h infusion of 2-chlorodeoxyadenosine (cladribine) with prednisone in previously untreated B-cell chronic lymphocytic leukaemia.

2-Chlorodeoxyadenosine (2-CdA) is a new antimetabolite chemotherapeutic agent active in indolent lymphoid malignancies. In this retrospective study, 69 previously untreated patients with B-cell chronic lymphocytic leukaemia (B-CLL) were treated with 2-CdA administered at a dose of 0.12 mg/kg daily in 2-h intravenous infusion for 5 consecutive days. 45 patients also received prednisone 30 mg/m2 orally each day for 5 days starting with 2-CdA courses. Patients were given 2-6 courses (mean 4.6) of 2-CdA repeated usually at monthly intervals. If a complete response was achieved, no further 2-CdA courses were administered. Guidelines for response were those developed by the NCI Sponsored Working Group. Complete response (CR) was achieved in 26 (38%) and partial response (PR) in 27 (39%) cases, giving an overall response rate of 77%. 16 patients (23%) did not respond to 2-CdA. In the subgroup of 45 patients receiving 2-CdA with prednisone, CR was obtained in 15 (33%) and PR in 20 (44%) patients giving an overall response rate of 78%. CR was achieved in 11 (46%) out of 24 patients treated only with 2-CdA and in 7 cases (29%) PR was observed, giving an objective response rate of 75%. The differences between both subgroups were not statistically significant. However, we observed a relationship between the response and the number of courses of 2-CdA given in patients receiving and those not receiving prednisone. In the subgroup receiving 2-CdA with prednisone, an earlier response to 2-CdA was observed. In this group a response was achieved in 9 (20%) patients after two courses of 2-CdA and in 18 (40%) after four courses. In the subgroup receiving only 2-CdA, 17 (71%) responses were obtained after six cycles.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

2-chlorodeoxyadenosine (2-CdA) in 2-hour versus 24-hour intravenous infusion in the treatment of patients with hairy cell leukemia.

Forty one patients with hairy cell leukemia (HCL) were treated with 2-chloro-deoxyadenosine (2-CdA) administered in various schedules. Complete remission (CR) was achieved in 31 (76%) patients and partial remission (PR) in 9 (22%). The mean duration of remission (CR + PR) was 25.2 months (range 9-45 months). One patient did not respond to therapy. Twelve out of 16 patients (75%) achieved CR after 5-day intravenous infusions of 2-CdA and 19 out of 25 patients (76%) after 7-day courses. In 19 out of 23 patients (82.6%) CR was achieved after intermittent 2-hour infusions and in 12 out of 18 (66.7%) after continuous 24-hour infusion. The differences were not statistically significant. Side effects of 2-CdA were similar in both groups except for infections, which were less frequently observed in the group treated for 5 days. The results of our study suggest that 2-CdA can be effectively administered to patients with HCL using 5-day courses and a 2-hour daily infusion.

Adult↗
PubMed1996

Intermittent 2-hour intravenous infusions of 2-chlorodeoxyadenosine in the treatment of 110 patients with refractory or previously untreated B-cell chronic lymphocytic leukemia.

The purpose of our study was to determine the effectiveness of 2-CdA in 2-hour intravenous infusions in the treatment of B-CLL. One hundred and ten patients with B-CLL received 1 to 10 courses of 2-CdA (median 2.5) at a dosage of 0.12 mg/kg daily for 5 consecutive days. Eighteen of them were untreated and 92 relapsed or became refractory to previous therapeutic modalities. Complete remission (CR) was achieved in 8 (7.3%) and partial remission (PR) in 35 patients (31.8%) giving an overall response rate of 39.1%. In 3 patients, cross-resistance to fludarabine was noticed. Toxic effects of 2-CdA were more frequently observed in previously treated patients. Hemorrhagic complications due to drug-induced thrombocytopenia were noticed in 25 (22.7%) and severe infections including sepsis in 14 (12.7%) patients.

Adult↗
PubMed1996

The first 15 minutes of hemodialysis does not affect platelets.

In the study, platelet count and volume, granulocyte number, binding of monoclonal antibodies to platelet glycoproteins Ib and IIb/IIIa were evaluated in hemodialyzed patients. Exclusively, the granulocyte count dropped significantly at 15 minutes after the initiation of dialysis as compared to predialysis samples. It seems that contemporary used cuprophane dialyzer membrane is more biocompatibile and does not have major impact on platelets.

Adult↗
PubMed1995

[Significance of histologic bone marrow evaluation in diagnosis of chronic granulocytic leukemia. II. Megakaryocytes].

In 40 non-treated, ph1-positive patients with chronic granulocytic leukaemia (CGL) statistically significant correlation between the number of megakaryocytes and Sokal's index was found. The comparison of the data concerning megakaryocytic-granulocytic type (with increased number of megakaryocytes) CGL and granulocytic type (classical) revealed that patients with increased number of megakaryocytes in bone marrow had significantly greater spleen, larger number of leukocytes, platelets and myeloblasts in peripheral blood, more advanced bone marrow fibrosis and higher Sokal's index. These data seem to suggest that patients with megakaryocytic-granulocytic type of CGL have worse prognosis than with classical type.

Adolescent↗
PubMed1995

[Significance of histologic bone marrow evaluation in chronic granulocytic leukemia diagnosis. III. Myeloblasts and promyelocytes].

The aim of the study was to assessment of the relationship between the number of myeloblasts in trephine biopsy in patients with chronic granulocytic leukaemia and Sokal's index. We have not found any correlation between these values. Further analysis revealed however that Sokal's index < 0.8 still qualified patients with evident signs of disease progress (increased number of layers of myeloblasts and promyelocytes in peri-trabecular and perivascular regions) to low risk group. We therefore conclude that bone marrow histology examination in chronic granulocytic leukaemia may bring valuable information concerning the real state of the disease.

Adolescent↗
PubMed1994

[Treatment outcome of advanced Hodgkin's disease based on using an alternating program ChLVPP (chlorambucil, vinblastine, procarbazine, prednisone) and ABV (doxorubicin, bleomycin, vinblastine)].

Twenty nine patients (7 women, 22 men) with III and IV stage of Hodgkin's disease were treated according to alternating programme ChLVPP/ABV. The results were evaluated in 27 patients. Complete remission was obtained in 41% (11 patients), partial remission in 22% (6 patients). Applied treatment revealed a relatively small toxicity.

Adult↗
PubMed1994

[Significance of histologic bone marrow evaluation in diagnosis of chronic granulocytic leukemia. I. Reticulin fibrosis].

The aim of the study was the evaluation of bone marrow reticulin fibrosis in non-treated patients suffering from chronic granulocytic leukaemia (cgl). We have examined 40 patients (19 female and 21 male, average age 41.2 years) with chronic phase, Ph'-positive cgl. Reticulin fibrosis grade I and II (according to Dekmezian and co.) was detected in 47.5% of patients and grade III and IV in 42.5%. Statistically significant correlation was found between reticulin fibrosis intensity and spleen size, platelets count and Sokal index. We believe that reticulin fibrosis assessment is of prognostic value.

Adolescent↗