Krzysztof Lewandowski

Publications of Krzysztof Lewandowski

• Microscopic examination of bone marrow aspirates in malignant disorders of haematopoiesis-a comparison of two slide preparation techniques.

  Authors: Krzysztof Lewandowski, Agnieszka Complak, Andrzej Hellmann

  Annals of hematology. 04/2012; 91(4):497-505.

  It is mandatory to perform microscopic examinations of bone marrow aspirates during the diagnosis of many neoplastic haematopoiesis disorders. In 2008, The International Committee for StandardizationIt is mandatory to perform microscopic examinations of bone marrow aspirates during the diagnosis of many neoplastic haematopoiesis disorders. In 2008, The International Committee for Standardization in Hematology recommended the use of two types of slides for the microscopic evaluation of bone marrow: wedge-spread film and crush film slides. Because these techniques have not yet been compared, we performed such a comparison. Routine bone marrow samples from 250 patients diagnosed due to different neoplastic haematological disorders were evaluated. The major differences between the two compared techniques were identified in 13 patients with non-Hodgkin's lymphoma, seven patients with systemic mastocytosis and 11 patients with acute leukaemias or myelodysplastic syndromes or chronic myelomonocytic leukaemia. Differences were noted also in many patients with multiple myeloma, but the clinical significance of these discrepancies was rather modest. The major causes of the differences observed seemed to be the dilution of marrow with blood cells and the focal growth of many neoplastic cells. We believe that the crush technique is more advantageous compared to the wedge-spread films. Therefore, we recommend the use of crush films as the primary method for establishing a diagnosis or for making therapeutic decisions based on the microscopic examination of bone marrow.

• A case of mast cell leukaemia with exon 9 KIT mutation and good response to imatinib.

  Authors: Andrzej Mital, Anna Piskorz, Krzysztof Lewandowski, Bartosz Wasąg, Janusz Limon, Andrzej Hellmann

  European journal of haematology. 03/2011; 86(6):531-5.

  Mastocytosis is a myeloproliferative neoplasm characterized by the excessive proliferation of mast cells. Mast cell leukaemia (MCL), the aggressive form of this disease, requires cytoreductiveMastocytosis is a myeloproliferative neoplasm characterized by the excessive proliferation of mast cells. Mast cell leukaemia (MCL), the aggressive form of this disease, requires cytoreductive therapy, such as cladribine, interferon-alpha-2b and, most recently, tyrosine kinase inhibitors - dasatinib or imatinib. We present a case of a 56-yr-old female patient with aleukaemic MCL in whom the typical KIT-D816V mutation was not detected. Sequencing of the entire coding sequence of KIT gene revealed a somatic mutation in exon 9 (p.A502_Y503dup). This mutation was previously reported in patients with gastrointestinal stromal tumours (GIST). Considering the good response to imatinib in such patients, therapy with imatinib was attempted in our patient. The treatment tolerance and outcomes were very good, with reduced mast cell infiltration of the bone marrow, normalization of the serum tryptase concentration and resolution of the clinical signs and symptoms. In the absence of the KIT-D816V in systemic forms of mast cell proliferation, a search for other mutations is indicated, preferably by sequencing the entire KIT gene, as this can influence the choice of treatment. The finding of the p.A502_Y503dup in exon 9, a mutation which has been observed in GIST but not previously reported in any form of aggressive mastocytosis, can be associated with a good response to imatinib in both diseases.

• Comparison of cladribine plus cyclophosphamide with fludarabine plus cyclophosphamide as first-line therapy for chronic lymphocytic leukemia: a phase III randomized study by the Polish Adult Leukemia Group (PALG-CLL3 Study).

  Authors: Tadeusz Robak, Krzysztof Jamroziak, Joanna Gora-Tybor, Beata Stella-Holowiecka, Lech Konopka, Bernadetta Ceglarek, Krzysztof Warzocha, Ilona Seferynska, Jaroslaw Piszcz, Malgorzata Calbecka, Aleksandra Kostyra, Jadwiga Dwilewicz-Trojaczek, Anna Dmoszyñska, Krystyna Zawilska, Andrzej Hellmann, Andrzej Zdunczyk, Stanislaw Potoczek, Magdalena Piotrowska, Krzysztof Lewandowski, Jerzy Z Blonski

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 03/2010; 28(11):1863-9.

  PURPOSE Little is known about comparison of the activity of different purine nucleoside analogs in chronic lymphocytic leukemia (CLL). We conducted a randomized phase III trial to compare efficacyPURPOSE Little is known about comparison of the activity of different purine nucleoside analogs in chronic lymphocytic leukemia (CLL). We conducted a randomized phase III trial to compare efficacy and safety of cladribine and fludarabine, each combined with cyclophosphamide, in previously untreated progressive CLL. PATIENTS AND METHODS Patients received cladribine at 0.12 mg/kg combined with cyclophosphamide at 250 mg/m(2) for 3 days intravenously (CC regimen) or fludarabine at 25 mg/m(2) combined with cyclophosphamide at 250 mg/m(2) for 3 days intravenously (FC regimen), every 28 days for up to six cycles. The primary end point was complete response (CR) rate. Secondary end points included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related toxicity. RESULTS Of 423 randomly assigned patients (211 to CC and 212 to FC), 395 were evaluated in the final analysis. The CR and ORR reached 47% and 88% in the CC arm and 46% and 82% in the FC arm (P = .25 and P = .11, respectively). The median PFS was 2.34 years with CC and 2.27 years with FC (P = .51). OS and grade 3/4 treatment-related toxicity were also comparable. Moreover, we did not observe any significant differences in CC and FC efficacy across different patient prognostic subgroups that included patients with 17p13 (TP53 gene) deletion who had poor survival in both study arms. CONCLUSION Cladribine and fludarabine in combination with cyclophosphamide are equally effective and safe first-line regimens for progressive CLL. Both combinations have unsatisfactory activity in patients with 17p13 (TP53 gene) deletion.

• [Standardization of quantitative detection of BCR-ABL gene expression by RQ-PCR in patients with chronic myeloid leukemia in cooperation with European Leukemia Net].

  Authors: Tomasz Sacha, Magdalena Zawada, Sylwia Czekalska, Izabela Florek, Martin Mueller, Michał Gniot, Bozena Jaźwiec, Sławomira Kyrcz-Krzemień, Aleksandra Leszczyńska, Krzysztof Lewandowski, Karolina Matiakowska, Iwona Solarska, Tomasz Stokłosa, Aleksander B Skotnicki

  Przegla̧d lekarski. 01/2010; 67(7):454-9.

  Monitoring of chronic myeloid leukemia treatment efficacy requires very sensitive methods of BCR-ABL gene detection based on polymerase chain reaction (PCR). The lack of comparability of BCR-ABL mRNAMonitoring of chronic myeloid leukemia treatment efficacy requires very sensitive methods of BCR-ABL gene detection based on polymerase chain reaction (PCR). The lack of comparability of BCR-ABL mRNA quantification results generated by various methodologies in different laboratories was the cause of an international multicenter trial initiation with the participation of 133 laboratories in 24 European countries cooperating within the "EUTOS for CML" project. Pracownia Diagnostyki Molekularnej Kliniki Hematologii is taking part in standardisation rounds organised since 2005. The compatibility of methodology used in Pracownia with European Leukemia Net (ELN) standards was confirmed, and correction factor for the expression of RQ-PCR results in an international scale was calculated. Pracownia was charge by ELN with a task of conducting the standardisation in polish molecular biology laboratories. Test probes were prepared and sent to eight cooperating laboratories. The results obtained in six laboratories were concordant with results from laboratory in Krakow after conversion to international scale, therefore it was possible to calculate individual correction factors. The participation of polish laboratories in international standardization process created the opportunity for unification of BCR-ABL quantification methodologies with recommendations of international experts, and showed that the quality of analyses performed in majority of them was satisfactory enough to calculate correction factor and to express the RQ-PCR results in widely accepted international scale.

• Frequency of BCR-ABL gene mutations in Polish patients with chronic myeloid leukemia treated with imatinib: a final report of the MAPTEST study.

  Authors: Krzysztof Lewandowski, Krzysztof Warzocha, Andrzej Hellmann, Aleksander Skotnicki, Witold Prejzner, Kajetana Foryciarz, Tomasz Sacha, Michał Gniot, Mirosław Majewski, Iwona Solarska, Grazyna Nowak, Bartosz Wasag, Mikołaj Kobelski, Cezary Scibiorski, Marek Siemiatkowski, Maria Lewandowska, Mieczysław Komarnicki

  Polskie archiwum medycyny wewnȩtrznej. 12/2009; 119(12):789-94.

  INTRODUCTION: The presence of BCR-ABL oncogene mutations in patients with chronic myeloid leukemia (CML) may be responsible for the failure of tyrosine kinase inhibitor treatment. OBJECTIVES: The aimINTRODUCTION: The presence of BCR-ABL oncogene mutations in patients with chronic myeloid leukemia (CML) may be responsible for the failure of tyrosine kinase inhibitor treatment. OBJECTIVES: The aim of the study was to evaluate the frequency of BCR-ABL gene mutations in patients with CML (the MAPTEST study) treated with imatinib (IM). PATIENTS AND METHODS: Direct sequencing analysis of BCR-ABL gene was performed in 92 patients treated with IM for more than 3 months. The mean time of IM treatment was 18 months. At the time of the analysis, 75 patients were in the first chronic phase (CP), 4 in the second CP, 5 in the acceleration and 8 in the blastic phase. Fifty-seven patients (62%) were treated with IM at a daily dose of 400 mg and 35 patients with higher doses (600 or 800 mg daily). Inclusion criteria were based on the European Leukemia Net definitions for failure and suboptimal response to IM. RESULTS: Twelve mutations were detected in 11 of 92 patients, including 4 mutations (36.7%) diagnosed during CP, 3 (27.3%) in acceleration, and 4 (36.7%) in blast crisis. In 1 patient with lymphoid blast crisis of CML coexisting F359V and Y253F mutations were detected. In the whole group mutations were detected in 2 of 5 patients (40%) with primary resistance (M351T, F359V + Y253F) and in 9 of 87 patients (10.3%) (E255K, T315I-3x, M351T, E355G, F359V-2x) with acquired resistance to IM. CONCLUSIONS: The study confirmed the usefulness of BCR-ABL gene mutation screening in patients with CML resistant to IM therapy.

• Dasatinib-induced complete molecular response after allogeneic hematopoietic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to prior imatinib-containing regimen: a case report and discussion.

  Authors: Anna Czyz, Krzysztof Lewandowski, Renata Kroll, Mieczysław Komarnicki

  Medical oncology (Northwood, London, England). 11/2009;

  Presence of the Philadelphia chromosome in acute lymphoblastic leukemia is the single most adverse prognostic marker associated with high risk of disease relapse and poor prognosis. AllogeneicPresence of the Philadelphia chromosome in acute lymphoblastic leukemia is the single most adverse prognostic marker associated with high risk of disease relapse and poor prognosis. Allogeneic haematopoietic stem cell transplantation is considered as the only curative option in adults with Philadelphia-positive acute lymphoblastic leukemia, but relapse remains the main cause of treatment failure. Moreover, long-term survival rates are markedly decreased when transplanted patients are not in complete remission. Incorporation of tyrosine kinase inhibitors into transplantation strategy in patients with Philadelphia-positive acute lymphoblastic leukemia may improve prognosis of the disease. Imatinib combined with conventional chemotherapy and used in conjunction with allogeneic hematopoietic stem cell transplantation has improved long-term survival rates. The more potent multikinase inhibitor dasatinib has shown enhanced activity in Philadelphia-positive acute lymphoblastic leukemia and has been approved for the treatment of adults with resistance or intolerance to prior imatinib therapy. Here, we present a case of Philadelphia-positive acute lymphoblastic leukemia primary resistant to imatinib combined with chemotherapy. Subsequently, the patient underwent allogeneic hematopoietic stem cell transplantation as a salvage therapy. Clinical evaluation performed thereafter revealed complete hematologic remission, but with the presence of the minimal residual disease detected at molecular level. Due to imatinib resistance, the therapy with dasatinib was started and complete molecular response was obtained. The consecutive clinical evaluation performed every 3 months during the last 18 months confirmed the absence of molecular minimal residual disease. We believe that inclusion of dasatinib into transplantation strategy allows obtaining sustained molecular remission even in patients resistant to imatinib.

• Status of minimal residual disease after induction predicts outcome in both standard and high-risk Ph-negative adult acute lymphoblastic leukaemia. The Polish Adult Leukemia Group ALL 4-2002 MRD Study.

  Authors: Jerzy Holowiecki, Malgorzata Krawczyk-Kulis, Sebastian Giebel, Krystyna Jagoda, Beata Stella-Holowiecka, Beata Piatkowska-Jakubas, Monika Paluszewska, Ilona Seferynska, Krzysztof Lewandowski, Marek Kielbinski, Anna Czyz, Agnieszka Balana-Nowak, Maria Król, Aleksander B Skotnicki, Wieslaw W Jedrzejczak, Krzysztof Warzocha, Andrzej Lange, Andrzej Hellmann

  British journal of haematology. 05/2008;

  The treatment of adults with Philadelphia-negative acute lymphoblastic leukaemia (ALL) depends on the presence of risk factors including age, white blood cell count, immunophenotype and time toThe treatment of adults with Philadelphia-negative acute lymphoblastic leukaemia (ALL) depends on the presence of risk factors including age, white blood cell count, immunophenotype and time to complete remission. In recent years, status of minimal residual disease (MRD) has been postulated as an additional risk criterion. This study prospectively evaluated the significance of MRD. Patients were treated with a uniform Polish Adult Leukemia Group (PALG) 4-2002 protocol. MRD status was assessed after induction and consolidation by multiparametric flow cytometry. Out of 132 patients included (age, 17-60 years), 116 patients were suitable for analysis. MRD level >/=0.1% of bone marrow cells after induction was found to be a strong and independent predictor for relapse in the whole study population (P < 0.0001), as well as in the standard risk (SR, P = 0.0003) and high-risk (P = 0.008) groups. The impact of MRD after consolidation on outcome was not significant. The combination of MRD status with conventional risk stratification system identified a subgroup of patients allocated to the SR group with MRD <0.1% after induction who had a very low risk of relapse of 9% at 3 years as opposed to 71% in the remaining subjects (P = 0.001). We conclude that MRD evaluation after induction should be considered with conventional risk criteria for treatment decisions in adult ALL.

• Bortezomib in combination with thalidomide and dexamethasone--a successful treatment regimen in refractory extramedullary multiple myeloma.

  Authors: Dominik Dytfeld, Magdalena Matuszak, Krzysztof Lewandowski, Mieczysław Komarnicki

  Annals of hematology. 04/2008; 87(3):253-4.

• Dasatinib treatment can overcome imatinib and nilotinib resistance in CML patient carrying F359I mutation of BCR-ABL oncogene.

  Authors: Marta Barańska, Krzysztof Lewandowski, Michał Gniot, Małgorzata Iwoła, Maria Lewandowska, Mieczysław Komarnicki

  Journal of applied genetics. 02/2008; 49(2):201-3.

  Point mutations of bcr-abl tyrosine kinase are the most frequent causes of imatinib resistance in chronic myeloid leukaemia (CML) patients. In most CML cases with BCR-ABL mutations leading toPoint mutations of bcr-abl tyrosine kinase are the most frequent causes of imatinib resistance in chronic myeloid leukaemia (CML) patients. In most CML cases with BCR-ABL mutations leading to imatinib resistance the second generation of tyrosine kinase inhibitors (TKI- e.g. nilotinib or dasatinib) may be effective. Here, we report a case of a CML patient who during imatinib treatment did not obtain clinical and cytogenetic response within 12 months of therapy. The sequencing of BCR-ABL kinase domains was performed and revealed the presence of a F359I point mutation (TTC-to-ATC nucleotide change leading to Phe-to-Ile amino acid substitution). After 1 month of nilotinib therapy a rapid progression of clinical symptoms was observed. In the presence of the F359I point mutation only dasatinib treatment overcame imatinib and nilotinib resistance.

• 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.

  Authors: Tadeusz Robak, Krzysztof Jamroziak, Joanna Gora-Tybor, Jerzy Z Blonski, Marek Kasznicki, Jadwiga Dwilewicz-Trojaczek, Elzbieta Wiater, Andrzej Zdunczyk, Jacek Dybowicz, Anna Dmoszynska [......] Aleksander B Skotnicki, Wieslaw Nowak, Krystyna Zawilska, Lucyna Molendowicz-Portala, Janusz Kloczko, Jaroslaw Sokolowski, Krzysztof Warzocha, Ilona Seferynska, Bernardeta Ceglarek, Lech Konopka

  Blood. 06/2007; 109(9):3672-5.

  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-CdACladribine (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.

• Presence of hepatitis C virus (HCV)-RNA in peripheral blood mononuclear cells in HCV serum negative patients during interferon and ribavirin therapy.

  Authors: Danuta Januszkiewicz-Lewandowska, Jacek Wysocki, Monika Pernak, Karina Nowicka, Mariola Zawada, Jolanta Rembowska, Krzysztof Lewandowski, Przemysław Mańkowski, Jerzy Nowak

  Japanese journal of infectious diseases. 03/2007; 60(1):29-32.

  Identification of hepatitis C virus (HCV)-RNA in blood serum is crucial for hepatitis C diagnosis and for appropriate treatment. Detection of HCV-RNA in blood serum is used for therapy monitoring ofIdentification of hepatitis C virus (HCV)-RNA in blood serum is crucial for hepatitis C diagnosis and for appropriate treatment. Detection of HCV-RNA in blood serum is used for therapy monitoring of patients with hepatitis C. Despite HCV-RNA elimination from blood serum during treatment in some patients, HCV viremia appears again after the completion of therapy. The aim of this study was to assess HCV-RNA in peripheral blood mononuclear cells (PBMCs) of hepatitis C patients in relation to HCV-RNA and antibodies to HCV in the serum. The study involved 71 patients undergoing anti-viral therapy (interferon and ribavirin). RNA isolated from serum and PBMCs was examined for the presence of HCV-RNA by an RT-PCR technique using specific oligonucleotide primers or by commercially available kits. In order to show the possible presence of HCV sequences in PBMCs, molecular DNA probes were constructed with a PCR amplicon and biotin-labelled by nick translation, and FISH and extended chromatin fibers in situ hybridization (ECFs-FISH) techniques were used. A 24-month follow-up study revealed that 34 out of 59 patients (58%) eliminated HCV-RNA from their sera. In the serum negative group, HCV-RNA was detected in PBMCs of 2 patients. The presence of HCV-RNA in PBMCs was confirmed by the FISH technique. In the ECFs-FISH procedure, no signal was found in all examined patients. Our data suggest that PBMCs infected with HCV can serve as a virus reservoir. HCV-RNA serum negative patients who have HCV-RNA in their leukocytes after completion of anti-viral therapy would be at great risk of hepatitis C recurrence. These HCV-RNA serum negative but PBMCs positive patients would be a potential source of HCV spread.

• Fludarabine, cytarabine, and mitoxantrone (FLAM) for the treatment of relapsed and refractory adult acute lymphoblastic leukemia. A phase study by the Polish Adult Leukemia Group (PALG).

  Authors: Sebastian Giebel, Malgorzata Krawczyk-Kulis, Maria Adamczyk-Cioch, Beata Jakubas, Grazyna Palynyczko, Krzysztof Lewandowski, Anna Dmoszynska, Aleksander Skotnicki, Katarzyna Nowak, Jerzy Holowiecki

  Annals of hematology. 10/2006; 85(10):717-22.

  Outcome of adults with acute lymphoblastic leukemia (ALL) who fail to achieve complete remission (CR) or who relapse soon after initial response is poor. The goal of this phase II study by the PolishOutcome of adults with acute lymphoblastic leukemia (ALL) who fail to achieve complete remission (CR) or who relapse soon after initial response is poor. The goal of this phase II study by the Polish Adult Leukemia Group (PALG) was to evaluate safety and efficacy of a new salvage regimen (FLAM) consisting of sequential fludarabine, cytarabine, and mitoxantrone. Fifty patients were included with primary (n = 13) or secondary (n = 5) refractoriness, early (<12 months) first relapse (n = 15), first relapse after hematopoietic cell transplantation (HCT) regardless CR duration (n = 13), and second or subsequent relapse (n = 4). Median age was 31(18-60) years, 28% of patients were bcr/abl-positive. CR rate equaled 50% and was significantly higher for patients in whom FLAM was administered as a second-line therapy compared to those more heavily pre-treated (66 vs 13%, p = 0.02). Seventeen patients had leukemia regrowth after initial cytoreduction, whereas, eight patients died in aplasia. The incidence of early death was higher in patients aged > or =40 years compared to the younger subgroup (33 vs 8%, p=0.03). Septic infections were the most frequent severe complication. At 3 years, the probability of disease-free survival for patients who achieved CR equaled 16%. Seven patients underwent allogeneic HCT. FLAM regimen is feasible for relapsed and refractory adults with ALL and could be recommended in particular for younger patients as a second-line treatment. However, as the remission duration is short, allogeneic HCT (alloHCT) should be considered as soon as possible.

• Amplification of hTERT and hTERC genes in leukemic cells with high expression and activity of telomerase.

  Authors: Tomasz Nowak, Danuta Januszkiewicz, Mariola Zawada, Monika Pernak, Krzysztof Lewandowski, Jolanta Rembowska, Karina Nowicka, Przemyslaw Mankowski, Jerzy Nowak

  Oncology reports. 09/2006; 16(2):301-5.

  Reactivation of telomerase plays an important role in carcinogenesis. Malignant cells almost always possess high activity and expression of telomerase. The aim of this study was to see whether thereReactivation of telomerase plays an important role in carcinogenesis. Malignant cells almost always possess high activity and expression of telomerase. The aim of this study was to see whether there is any relationship between telomerase activity and expression and hTERT and hTERC gene amplification in acute lymphoblastic leukemia (ALL) and non-lymphoblastic leukemia (ANLL) cells. In addition telomere length was tested in leukemic cells at the time of diagnosis and during remission. Expression of the three components of telomerase (hTERT, hTERC and TP1) as well as telomerase activity was found both in ALL and ANLL cells. Telomerase activity was diminished in patients in remission. The leukemic cells showed considerable heterogeneity of terminal restriction fragments, that is telomere length. ALL cells showed a variable pattern of telomere length in contrast to ANLL cells which produced a predominantly short telomere pattern. Telomere length in the lymphocytes of leukemia patients was shorter in remission as compared to the time of diagnosis. FISH analysis revealed amplification of hTERT and hTERC genes in ALL and ANLL cells. Quantitative analysis showed that leukemic cells possess higher number of hTERT and hTERC copies than the normal PBL. Our results suggest that the activation of telomerase in leukemic cells is connected with amplification of hTERT and hTERC genes. The high expression and activity of telomerase found in leukemic cells may be partially explained by amplified hTERT and hTERC genes. Amplification of the telomerase genes seems to be a common event in carcinogenesis and may play a role in telomerase reactivation leading to cell immortalization.

• Cancer procoagulant in patients with adenocarcinomas.

  Authors: Maciej Kaźmierczak, Krzysztof Lewandowski, Marek Z Wojtukiewicz, Zofia Turowiecka, Edyta Kołacz, Anna Lojko, Elzbieta Skrzydlewska, Krystyna Zawilska, Mieczysław Komarnicki

  Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 12/2005; 16(8):543-7.

  Cancer procoagulant (CP) is a cysteine proteinase that may be produced by malignant and foetal tissue. The possible role of CP in the pathogenesis of cancer-related thrombosis has been suggestedCancer procoagulant (CP) is a cysteine proteinase that may be produced by malignant and foetal tissue. The possible role of CP in the pathogenesis of cancer-related thrombosis has been suggested recently. The purpose of the study was to evaluate coagulation prothrombotic markers and their relation to CP concentration in the blood of patients with gastrointestinal adenocarcinomas (GIAC). The study group consisted of 45 patients with confirmed diagnosis of adenocarcinoma (stomach, 18 patients; colon, 27 patients) and without evident metastatic disease. In 24 patients further observation showed metastases. The control group for CP was composed of 10 healthy subjects. Blood samples were drawn on the admission day, before any treatment. Among 45 patients with GIAC, deep venous thrombosis was observed in two (4.4%). In all patients the CP activity in the serum was found, and the mean CP activity shortened the coagulation time almost three times compared with the healthy control group. Also, the mean thrombin-antithrombin complex concentration was above the normal range. A significant elevation of the mean prothrombin fragment 1+2 plasma content in this group of patients was noticed. Despite these observations, CP remained within the normal range and did not correlate with thrombin-antithrombin complex or prothrombin fragment 1+2 plasma concentrations. A positive correlation was observed between serum CP and fibrinogen concentration, and a negative correlation between CP and free protein S plasma content (P = 0.04 and P = 0.025, respectively). A negative correlation between activated protein C resistance ratio and protein C activity in the plasma was confirmed. Protein C activity in the plasma showed a correlation with free protein S plasma content. Analysis of factors influencing the activated partial thromboplastin time revealed the presence of antiphospholipid antibodies in seven persons from the study group (in three cases of IgG and in four cases of IgM class). Our data suggest that CP is a minor risk factor for deep venous thrombosis in GIAC patients. To confirm this, however, the number of patients and controls should be larger. After 3 years of observation, the follow-up in 10 living GIAC patients showed nobody with thromboembolic disease.

• 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).

  Authors: Tadeusz Robak, Jerzy Z Błoński, Marek Kasznicki, Joanna Góra-Tybor, Anna Dmoszyńska, Maria Wojtaszko, Aleksander B Skotnicki, Wiesław Nowak, Andrzej Hellmann, Krzysztof Lewandowski, Barbara Zdziarska, Lech Konopka, Bernadetta Ceglarek, Jadwiga Dwilewicz-Trojaczek, Piotr Boguradzki, Kazimierz Kuliczkowski, Kazimierz Sułek, Krzysztof Warzocha

  Medical science monitor : international medical journal of experimental and clinical research. 10/2005; 11(10):PI71-9.

  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 inBACKGROUND: 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.

• The prevalence of C807T mutation of glycoprotein Ia gene among young male survivors of myocardial infarction: a relation with coronary angiography results.

  Authors: Krzysztof Lewandowski, Anna Swierczyńska, Piotr Kwaśnikowski, Waldemar Elikowski, Mirosław Rzeźniczak

  Kardiologia polska. 09/2005; 63(2):107-13; discussion114.

  INTRODUCTION: The glycoprotein complex Ia/IIa (GP Ia/IIa) is a major collagen receptor on platelets and other cell types. Recently, linked polymorphisms within the coding region of the GP Ia geneINTRODUCTION: The glycoprotein complex Ia/IIa (GP Ia/IIa) is a major collagen receptor on platelets and other cell types. Recently, linked polymorphisms within the coding region of the GP Ia gene (C807T and G873A) related to GP Ia/IIa surface expression have been identified. The 807T/873A allele is associated with high expression, whereas the 807C/873G allele is associated with low surface expression of GP Ia/IIa. Subsequently, the 807T allele was found to be associated with coronary artery disease (CAD) and cerebral infarction in younger patients. Moreover, platelet thrombus formation is significantly influenced by genetic variations of the GPIb alpha and GPIa receptors and is dependent on the blood flow rate. AIM: 1. To determine the frequency of C807T polymorphism of the GPIa gene in young survivors of myocardial infarction (MI) and 2. to evaluate the relationship between the intensity of CAD in the coronary angiography examination and the 807C/T genetic status of the patients. METHODS: 102 young male survivors of MI (YSMI) -- mean age 43, range 29-49 years, mean age at the time of the first episode 37+/-3 years -- were studied. Obesity was found in 15%, diabetes in 14%, hyperlipidemia in 87%, hypertension in 22% and smoking history in 90% of cases. Familial CAD and/or MI were confirmed in 50% of patients. The control group consisted of 106 healthy volunteers with a negative family history of CAD, both medical staff members and blood donors (mean age 40, range 18-42 years). The genetic study was performed using genomic DNA obtained from peripheral blood leukocytes. The C807T polymorphism of platelet glycoprotein Ia (GPIa) was investigated using the PCR method introduced by Santoso et al. RESULTS: Coronary angiography (Siemens Bicor system) revealed single-artery disease in 34%, two-artery disease in 36% and three-artery disease in 26% of patients. In two patients there were no signs of CAD. The C807T polymorphism of GPIa was found in 73.5% of investigated patients (heterozygotes CT 59.8%, homozygotes TT 13.7%). The CC genotype was confirmed in 26.5% of patients. A similar analysis performed in the group of healthy men showed C807T polymorphism of the GPIa gene in 73.6% (CT in 58.5% and TT in 15.1% of persons, ns). CC genotype was found in 26.4% of persons. Interestingly, the T genotype frequency was similar in patients with three- or two-artery disease in comparison with patients with single-vessel or without CAD (49.3% vs. 50.7%, respectively, ns). In 75 YSMI carrying C807T polymorphism of the GPIa gene additional genetic abnormalities were confirmed in 21 patients - BclI polymorphism of b-chain fibrinogen gene, G4070A and G1691A (FV Leiden) mutation of factor V gene and C677T polymorphism of methylenetetrahydrofolate reductase gene. Partial occurrence of combined polymorphisms was found. This was confirmed independently of the number of coronary arteries involved.CONCLUSIONS: Our results may question the potential role of C807T the GPIa anomaly as a single genetic abnormality predisposing young men to coronary artery disease.

• [The role of thrombin activatable fibrinolysis inhibitor in disturbances of fibrinolytic system in obesity]

  Authors: Edyta Kołacz, Krzysztof Lewandowski, Krystyna Zawilska

  Polskie archiwum medycyny wewnȩtrznej. 06/2005; 113(5):424-30.

  The aim of the study was to evaluate fibrinolysis in obese women. Study group consisted of 45 obese women (mean age 36,8 +/- 16,6 years, mean BMI 35,7 +/- 4,9), who were allocated to two subgroups:The aim of the study was to evaluate fibrinolysis in obese women. Study group consisted of 45 obese women (mean age 36,8 +/- 16,6 years, mean BMI 35,7 +/- 4,9), who were allocated to two subgroups: premenopausal (mean age 32,3 +/- 9,9 years, mean BMI 36,9 +/- 5,6) and postmenopausal (mean age 64,8+/-10,1 years, mean BMI 33,3 +/- 2,55). Control group consisted of 45 women (mean age 35,3 +/- 13,9 years) with normal BMI (21,8 +/- 3,09). Global fibrinolytic activity was diminished only in obese women after menopause. Final analysis revealed significant increase of TAFI antigen and activity in the plasma of obese women. The existence of significant correlation in multifactor regression analysis between TAFI plasma content and euglobulin clot lysis time (ECLT) and global fibrinolytic capacity (GFC) as well confirmed negative influence of this inhibitor on fibrinolytic capacity in obese women. The increase of TAFI antigen and activity in the plasma was independent of age, BMI, glucose, cholesterol, triglicerides, insulin and leptin concentration in the plasma. The results of ECLT and GFC may be also influenced by PAI-1 activity particularly in women before menopause, which was significantly elevated in our group of patients. This increase as not dependent with TAFI antigen concentration. In conclusion, the observed increase TAFI antigen and activity in the plasma of obese women may influence the thrombotic risk in this group of patients, especially after menopause.

• [Systemic mastocytosis]

  Authors: Marek Niedoszytko, Magdalena Lange, Marta Chelminska, Kazmierz Jaśkiewicz, Anna Piskosz, Bartosz Wasag, Krzysztof Lewandowski, Andrzej Mital, Joanna Renke, Marta Gruchała-Niedoszytko, Michał Woźniak, Anna Babińska, Ewa Jassem

  Pneumonologia i alergologia polska : organ Polskiego Towarzystwa Ftyzjopneumonologicznego, Polskiego Towarzystwa Alergologicznego, i Instytutu Gruźlicy i Chorób Płuc. 02/2005; 73(3):239-44.

  Mastocytosis is group of rare disorders characterized by abnormal mast cells growth. Pathology of the disease is unknown, mechanisms involved in mast cells delineation and growth are considered toMastocytosis is group of rare disorders characterized by abnormal mast cells growth. Pathology of the disease is unknown, mechanisms involved in mast cells delineation and growth are considered to play an important role. Unusual and broad spectrum of symptoms therefore requires cooperation of different specialists. The aim of the study was to assess diagnostic and therapeutic methods used in the Gdansk Mastocytosis Centre. 14 patients were studied (9 adults and 5 children). Bone marrow biopsy was performed in order to assess the stage of disease. Pathological, cytological, cytofotometry and genetic examination (C-KIT mutation) of the bone marrow were performed. Patients suffereing from food allergy and wasp venom anaphylaxis were diagnosed with skin prick tests and sIgE. All subjects suffered from urticaria pigmenthosa and anaphylaxis. Indolent mastocytosis was diagnosed in six subjects. Patients were treated with antihistamines, corticosteroids, cromones and immunotherapy with a marked reduction of symptoms. The experience of Gdansk Mastocytosis Centre indicates that mastocytosis is a rare and difficult to diagnose disease.

• [Recent advances in the diagnosis of von Willebrand disease]

  Authors: Krzysztof Lewandowski, Marta Barańska

  Polskie archiwum medycyny wewnȩtrznej. 10/2004; 112(3):1141-9.

• Lack of correlation between telomere length and telomerase activity and expression in leukemic cells.

  Authors: Danuta Januszkiewicz, Jacek Wysoki, Krzysztof Lewandowski, Monika Pernak, Karina Nowicka, Jolanta Rembowska, Jerzy Nowak

  International journal of molecular medicine. 01/2004; 12(6):935-8.

  The expression of three components of telomerase complex (hTR, hTERT, TP1) along with telomerase activity and telomere length in leukemic cells was investigated. Cells were isolated from peripheralThe expression of three components of telomerase complex (hTR, hTERT, TP1) along with telomerase activity and telomere length in leukemic cells was investigated. Cells were isolated from peripheral blood and/or bone marrow of children with acute lymphoblastic (ALL) and non-lymphoblastic (ANLL) leukemia. Expression of three components of telomerase as well as telomerase activity was found in all leukemic cells. Chemiluminescent detection of terminal restriction fragments (TRF) from DNA isolated from ALL cells showed variable patterns expressing considerable heterogeneity of telomere length. The ALL cells appeared to have both long and short telomere lengths, in contrast to normal peripheral lymphocytes, which produced limited pattern of TRF. The ANLL cells produced predominantly short telomere pattern despite high telomerase activity and expression. It can be concluded that high telomerase activity and expression in leukemic cells is not always correlated with long telomeres (TRF pattern).