Janusz Kloczko

Silesian University of Technology, Gleiwitz, Silesian Voivodeship, Poland

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Publications (53)261.91 Total impact

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    ABSTRACT: Purpose The importance of allogeneic hematopietic stem cell transplantation (allo-HSCT) for survival outcomes in AML patients currently remains unclear. The study aimed to compare measures of clinical treatment for AML patients in CR1 (the first complete remission) with or without being subjected to allo-HSCT. These consisted of leukemia-free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR) and non-relapse mortality disease (NRM). Findings Subjects were 622 patients, median age of 44, forming part of the prospective, randomized and multicenter clinical Polish Adult Leukemia Group trials during 1999-2008. The Mantel-Byar approach was used to assess allo-HSCT on survival endpoints, accounting for a changing transplant status. Undergoing allo-HSCT significantly improved the LFS and OS for the entire group of AML patients in CR1, along with the DAC induction subgroup and for the group with unfavorable cytogenetics aged 41-60. The CIR demonstrated that allo-HSCT reduced the risk of relapse for AML patients in CR1 and those with an unfavorable cytogenetic risk. In addition, the NRM analysis showed that allo-HSCT significantly reduced the risk of death unrelated to relapse for the entire group of AML patients in CR1 and aged 41-60. Conclusions The allo-HSCT treatment particularly benefitted survival for the AML in CR1 group having an unfavorable cytogenetic prognosis. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Jul 2015 · American Journal of Hematology
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    ABSTRACT: INTRODUCTION: Recent studies in mouse model of chronic lymphocytic leukemia (CLL) demonstrated that inhibition of programmed death receptor - 1 (PD-1)-PD-L1 axis resulted in correction of leukemia-induced CD8+ T cell-related immune dysfunction and protected mice from CLL development. It remains unclear whether CLL development and progression can also be associated with CD4+ T cells expressing PD-1. OBJECTIVES: Here we set out to analyze whether quantitative assessment of CD4+PD-1+ T cells performed at the time of diagnosis can improve prognostication in CLL patients. PATIENTS AND METHODS: We examined 56 patients with newly diagnosed B-CLL at different stages of disease. The frequencies of PD-1 expressing CD4+ T cells were assessed by means of flow cytometry in all studied individuals. RESULTS: We demonstrated that CLL patients with advanced, high-risk disease and intermediate-risk presented with significantly higher frequencies of CD4+PD-1+ T cells compared to subjects with low grade disease. Notably, we showed that frequencies of PD-1 expressing CD4+ T cells in CLL patients qualified for immediate treatment due to the advanced stage of their disease were significantly higher compared to subjects qualified for the "wait and watch" strategy. Finally, we found that treatment-naïve "wait and watch" CLL patients with higher baseline numbers of CD4+PD-1+ T cells showed a significantly shortened time to the first treatment compared to CLL patients with lower CD4+PD-1+ T cells frequencies. CONCLUSIONS: In summary, our findings indicate that flow-cytometry-based evaluation of PD-1 on peripheral blood CD4+ T cells could improve prognostication of newly diagnosed treatment-naïve CLL patients.
    No preview · Article · Jul 2015 · Polskie archiwum medycyny wewnȩtrznej
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    ABSTRACT: Three main monocyte subsets: classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++, differentially regulate tumor growth and survival. Thereby, in the present study we aimed to determine the role of distinct monocyte subsets in the prognostication of chronic lymphocytic leukemia (CLL). Moreover, we set out to analyze the effects of standard immune chemotherapy on different monocyte subsets and levels of membrane-associated and soluble forms of CD163, a monocyte/macrophage-related immunomodulatory protein. We demonstrated that the number of peripheral blood classical CD14++CD16- monocytes assessed at the time of diagnosis was negatively correlated with lymphocytosis and was decreased in the CLL patients who required immediate treatment as opposed to patients who qualified to 'watch and wait' strategy. Notably, lower baseline levels of classical CD14++CD16- monocytes in CLL patients who were qualified for 'watch and wait' therapy were associated with shorter time to initial treatment. Notably, therapy with rituximab, cyclophosphamide and fludarabine resulted in a significant reduction in the number of non-classical CD14+CD16++ monocytes and soluble form of CD163 but upregulation of membrane-associated monocyte CD163. Our data indicate that distinct monocyte subsets and two forms of CD163 are differentially modulated by both CLL and immune chemotherapy. Moreover, we proposed that quantification of classical monocytes at the time of diagnosis contributes to better prognostication of CLL patients.
    No preview · Article · Jun 2015 · Oncology Reports
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    ABSTRACT: Background Recently, identification of CD25 (interleukin-2 receptor alpha) expression on leukemic blasts was correlated to early treatment failure and unfavorable outcome in acute myeloid leukemia (AML) patients. Here we wished to determine whether quantification of CD25 on peripheral blood CD4+ T cells could improve prognostication in newly diagnosed AML patients. Methods The mean fluorescence intensity (MFI) of CD25 expression and frequencies of peripheral blood CD4+ T cells with varying levels of CD25 and CD127 expression were assessed by flow cytometry in all studied individuals. Results Using univariate (unadjusted) and multivariate (adjusted) analyses we demonstrated that detection of high pretreatment CD25 expression on circulating CD4+ T cells was associated with significantly decreased survival rate of AML patients subjected to standard induction chemotherapy. These associations held true for both entire group of analyzed AML patients and different subgroups of patients identified by presence or absence of favorable and adverse molecular prognostic factors. Conclusions Our data indicate that quantification of CD25 expression on peripheral blood CD4+ T cells could become a novel, easily accessible method of shortened survival prognostication of AML patients subjected to standard cytotoxic therapy.
    No preview · Article · Jun 2015 · Pharmacological reports: PR
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    ABSTRACT: Treatment for patients with chronic lymphocytic leukaemia who are elderly or who have comorbidities is challenging because fludarabine-based chemoimmunotherapies are mostly not suitable. Chlorambucil remains the standard of care in many countries. We aimed to investigate whether the addition of ofatumumab to chlorambucil could lead to better clinical outcomes than does treatment with chlorambucil alone, while also being tolerable for patients who have few treatment options. Methods: We carried out a randomised, open-label, phase 3 trial for treatment-naive patients with chronic lymphocytic leukaemia in 109 centres in 16 countries. We included patients who had active disease needing treatment, but in whom fludarabine-based treatment was not possible. We randomly assigned patients (1: 1) to receive oral chlorambucil (10 mg/m(2)) on days 1-7 of a 28 day treatment course or to receive chlorambucil by this schedule plus intravenous ofatumumab (cycle 1: 300 mg on day 1 and 1000 mg on day 8; subsequent cycles: 1000 mg on day 1) for three to 12 cycles. Assignment was done with a randomisation list that was computer generated at GlaxoSmithKline, and was stratified, in a block size of two, by age, disease stage, and performance status. The primary endpoint was progression-free survival in the intention-to-treat population and assessment was done by an independent review committee that was masked to group assignment. The study is registered with ClinicalTrials.gov, number NCT00748189. Findings: We enrolled 447 patients, median age 69 years (range 35-92). Between Dec 22, 2008, and May 26, 2011, we randomly assigned 221 patients to chlorambucil plus ofatumumab and 226 patients to chlorambucil alone. Median progression-free survival was 22.4 months (95% CI 19.0-25.2) in the group assigned to chlorambucil plus ofatumumab compared with 13.1 months (10.6-13.8) in the group assigned to chlorambucil only (hazard ratio 0.57, 95% CI 0.45-0.72; p
    Full-text · Article · Apr 2015 · The Lancet
  • Anna Szumowska · Marzenna Galar · Lukasz Bolkun · Janusz Kloczko
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    ABSTRACT: The pathological consequences of decreased protein Z (PZ) and/or Z-dependent protease inhibitor (ZPI) levels remain as yet unclear, despite a growing body of evidence which supports their involvement in an increased thrombotic risk. The purpose of the present study was 2-fold: to evaluate plasma concentrations of protein Z and ZPI in patients with essential thrombocythemia (ET) and to determine their significance in thrombotic complications. The median (range) plasma concentrations of PZ in our patients with ET were lower, but not significantly, than in healthy individuals: PZ (1.42 µg/mL, 0.36-3.14 µg/mL vs 1.6 µg/mL, 0.75-2.56 µg/mL, P = .08). On the other hand, the median (range) plasma concentrations of ZPI in the said patients with ET were meaningfully lower than in the reference group: ZPI (3.22 µg/mL, 0.85-6.97 µg/mL vs 4.41 µg/mL, 1.63-7.83 µg/mL, P = .0004). More importantly, the study revealed a statistically significant lower concentration of PZ and ZPI in patients with the presence of the JAK2V617F mutation relative to patients without the mutation, for PZ: 1.38 µg/mL, 0.36-2.6 µg/mL versus 1.63 µg/mL, 0.88-3.14 µg/mL, P = .03, and ZPI 2.89 µg/mL, 0.85-5.91 µg/mL versus 3.61 µg/mL, 1.53-6.97 µg/mL, P = .002. Additionally, significant differences between the concentrations of PZ and ZPI were found in patients with venous thrombotic episodes compared to healthy individuals, for PZ: 1.23 µg/mL, 0.82-1.99 µg/mL versus 1.6 µg/mL, 0.75-2.56 µg/mL, P = .043, and ZPI: 2.42 µg/mL, 0.85-4.21 µg/mL versus 4.41 µg/mL, 1.63-7.83 µg/mL, P < .0001. To recapitulate, our results suggest that the deficiency of PZ may increase tendency to thrombosis in patients with ET. © The Author(s) 2015.
    No preview · Article · Mar 2015 · Clinical and Applied Thrombosis/Hemostasis
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    ABSTRACT: Altered activities of ligands belonging to tumour necrosis factor (TNF) superfamily, namely B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and apoptosis inducing ligand (TRAIL) were demonstrated in several haematological diseases including acute lymphoblastic leukaemia (ALL). BAFF, APRIL and TRAIL provide crucial survival signals to immature, naive and activated B cells. These ligands are capable of activating a broad spectrum of intracellular signaling cascades that can either induce apoptosis or protect from programmed cell death. BAFF and APRIL, which can directly activate the NF - κB pathway, have been identified as crucial survival factors for ALL cells. Here, we have analysed serum BAFF, APRIL and TRAIL concentrations in 48 patients with newly diagnosed ALL and 44 healthy volunteers. The levels of APRIL and BAFF were significantly higher in ALL patients as compared to healthy volunteers. In contrast, concentrations of TRAIL were significantly lower in ALL patients. Moreover, following induction, the levels of APRIL, but not BAFF or TRAIL, were significantly lower in a group of patients with complete remission (CR) as compared to non-respondent (NR) ALL patients. Furthermore, we demonstrated statistically significant differences in concentrations of APRIL between CR MRD-negative and CR, MRD-positive ALL patients. Notably detection of higher concentrations of APRIL was associated with shorter leukaemia-free survival and overall survival. Altogether, our data indicate that APRIL can play an important role in the pathogenesis of ALL and the measurement of APRIL levels can improve prognostication in ALL patients.
    No preview · Article · Dec 2014 · Leukemia Research
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    ABSTRACT: ABSTRACT This prospective study has estimated outcomes in 509 elderly AML patients with different treatment approaches depending on ECOG performance status and the Charlson Comorbidity Index (CCI). Patients were stratified into fit (ECOG 0-2 and CCI 0-2) or frail (ECOG >2 and/or CCI >2) groups. The fit patients with CCI 0 received intensive chemotherapy whilst reduced-intensive chemotherapy (R-IC) was given to those with CCI 1-2. The frail patients received the best supportive therapy. The fit patients presented a longer overall survival (OS) than frail subjects but 8-week mortality rates were similar. The CR ratio between fit CCI 0 and CCI 1-2 subgroups was significantly different. Both of the fit subgroups showed similar 8-week mortality rates and OS probabilities. Allocating the fit patients with CCI 1-2 to R-IC enabled to increase the group of elderly patients who could be treated with the intention of inducing remission.
    No preview · Article · Nov 2014 · Leukemia and Lymphoma
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    ABSTRACT: Tumour necrosis factor-alfa (TNF-α) is an inflammatory cytokine with a wide spectrum of biological activity, including angiogenesis. Tumour necrosis factor-related apoptosis inducing ligand (TRAIL), which belongs to the TNF family of proteins, plays a role in the regulation of vascular responses, but its effect on the formation of new blood vessels (angiogenesis) is unclear. We analysed TRAIL concentrations in parallel with pro-angiogenic cytokines in serum and their expression in trephine biopsy (TB) in 56 patients with newly diagnosed IgG MM and 24 healthy volunteers. The study showed statistically higher concentrations of TRAIL and TNF-α, as well as of VEGF and its receptor, in MM patients compared to healthy volunteers and patients in advanced stages of the disease. Furthermore, we observed a significant decrease in all studied pro-angiogenic cytokines and significant increase of TRAIL concentration after anti-angiogenic therapy, with meaningful differences between responders (at least partial remission) and patients with progression during the induction treatment. It was also established that TRAIL correlated statistically and negatively with pro-angiogenic cytokines such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB.In summary, our data indicate that in MM patients, both clinical course and treatment responsiveness are associated with dynamic yet corresponding changes of levels of TRAIL parallel pro-angiogenic mediators such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB. Copyright © 2014 John Wiley & Sons, Ltd.
    No preview · Article · Nov 2014 · Hematological Oncology
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    ABSTRACT: B cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL) and apoptosis-inducing ligand (TRAIL) were demonstrated in several haematological diseases including acute myeloid leukemia (AML). Those cytokines are capable of activating a broad spectrum of intracellular signalling cascades that can either induce apoptosis or protect from programmed cell death. We have analysed BAFF, APRIL and TRAIL serum concentrations in 76 patients with newly diagnosed AML and 40 healthy volunteers. The values were significantly higher for APRIL and BAFF but lower for TRAIL compared to healthy volunteers. Induction therapy significantly reduced the values for BAFF and increased them for TRAIL. Moreover, the concentration of BAFF and APRIL was significantly lower and the concentration of TRAIL higher in a group of patients with complete remission compared to non-respondent AML patients. In addition, higher concentrations of BAFF and lower of TRAIL predicted a shorter overall survival, suggesting thereby an important prognostic marker and possible therapeutic target in AML.
    Preview · Article · Aug 2014 · Annals of Hematology
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    ABSTRACT: The ubiquitin-proteasome pathway is implicated in the pathogenesis of many haematologic malignancies, including multiple myeloma. Under conditions of rapid cell turnover and growth rate, proteasomes are returned into circulation. The measurement of their levels or activity could offer a new approach to diagnosis, prognosis and monitoring of anticancer treatment in carcinoma patients. We analysed proteasome concentration and chymotrypsin-like (ChT-L) activity in the plasma of 64 patients with a newly diagnosed multiple myeloma and 30 healthy volunteers. The values were found to be significantly higher in the studied patients and advanced disease stages compared to the control group, and decreased significant after chemotherapy. Both proteasome concentration and ChT-L activity correlated with adverse prognostic factors, such as lactate dehydrogenase and β2-macroglobulin. We also showed that proteasome concentration positively correlates with IL-6 level, as opposed to proteasome ChT-L activity. Of note, higher proteasome ChT-L activity, unlike the concentration, was proved to be an indicator of a shorter progression free survival, constituting thereby an important prognostic marker.
    No preview · Article · Aug 2014 · Leukemia Research
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    ABSTRACT: CD37 is a tetraspanin protein expressed on the surface of normal and transformed B-cells across a wide range of maturational stages and demonstrates death signaling via SHP1. Otlertuzumab is a CD37-specific therapeutic protein built on the ADAPTIRTM(modular protein technology) platform that has shown significantly greater direct killing of CLL cells than rituximab and higher levels of Fc mediated cellular cytotoxicity of CLL cells than either alemtuzumab or rituximab in pre-clinical models. Preclinical in vitro and in vivo models showed significant activity of otlertuzumab with bendamustine (benda). In phase 1 of this study involving 12 relapsed and/or refractory CLL patients (pts), otlertuzumab plus benda was well tolerated and showed a positive response. This phase 2 trial was conducted to investigate the activity of this combination compared to benda alone. Methods Pts with relapsed CLL who had 1-3 prior treatments, adequate organ function, ECOG performance status ≤2, ANC ≥1200/μL and CrCl >40 mL/min were eligible. Pts were stratified at randomization based on Cumulative Illness Rating Score, CrCl and deletion or mutation of 17p13.1. Pts in the study drug arm received otlertuzumab (20 mg/kg) weekly by IV infusion for two 28-day cycles then every 14 days for four 28-day cycles. In both arms, benda (70 mg/m2) was administered IV on Days 1 and 2 of each cycle for up to six 28-day cycles. Safety was evaluated using CTCAE and IWCLL 2008 Grading scale for Hematologic Toxicity in CLL Studies. Response was determined using the 1996 NCI and 2008 IWCLL Criteria. Flow cytometry was performed on peripheral blood to quantitate and characterize lymphocyte populations. Results 65 pts have been treated in the randomized portion of the study, including 32 with otlertuzumab plus benda and 33 with benda alone. Pt characteristics and adverse events (AEs) are shown in the table. To date, 44 patients are evaluable for response assessment by the IWCLL criteria assessed 2.5 months after completion of therapy utilizing investigator assessment of CT scan and bone marrow data. The ORR for the combination of otlertuzumab and benda (n=20) was 80% (16) with a CR rate of 20% (4). For benda alone (n=24) the ORR was 42% (10) with a CR rate of 4% (1). Patients are still in treatment and follow-up but only 10% (2) have progressed on the combination of otlertuzumab and benda while 46% (11) have progressed on benda. The best response at anytime by NCI criteria using available data for the combination of otlertuzumab and benda (n=32) was ORR 78% and CR 16% and for benda alone (n=33) ORR 52% and CR 9%. There were no responses among pts with del17p; among pts with 17p mutation both pts in the combination arm had a response; no pts in the benda alone arm had a response. The frequency of all AEs was similar between treatment arms; hematologic and infection AEs were the most frequent in both arms. There were 13 serious AEs reported by 10 pts in the otlertuzumab+benda arm and 25 reported by 12 pts in the benda alone arm. The half-life of otlertuzumab is 11 days and there was no antidrug antibody in the 14 pts tested to date. View popupView inline Conclusions Preliminary response rate with otlertuzumab in combination with benda was higher than benda alone by IWCLL or NCI response criteria. The overall incidence of AEs was similar between the 2 treatment cohorts, with a higher incidence of pyrexia, neutropenia and thrombocytopenia with the combination. However, the addition of otlertuzumab did not appear to increase the number of serious adverse events.
    Full-text · Conference Paper · Dec 2013
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    ABSTRACT: Tumour necrosis factor alpha (TNF-α) is an inflammatory cytokine with a wide spectrum of biological activity, including angiogenesis. B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are members of the TNF-α family. Vascular endothelial growth factor (VEGF), on the other hand, is one of the most characteristic pro-angiogenic cytokines produced by multiple cell types in multiple myeloma (MM). We have analysed BAFF and APRIL concentrations in parallel with pro-angiogenic cytokines in serum and trephine biopsy, and the bone marrow microvascular density (MVD) in 50 patients with newly diagnosed IgG MM and 24 healthy volunteers. The study showed statistically higher concentrations of BAFF, APRIL and TNF-α, as well as VEGF and its receptor, in MM patients compared to healthy volunteers and patients in advanced stages of the disease. A statistically positive correlation between the concentration of TNF-α and the expression of VEGF was demonstrated, and so was a positive link between BAFF, APRIL, MVD and lactate dehydrogenase (LDH). Furthermore, we observed a significant decrease in all studied cytokines after anti-angiogenic therapy, with meaningful differences between responders (at least partial remission) and patients with stable disease. It was also established that APRIL, but not BAFF, correlated with pro-angiogenic cytokines such as VEGF with its receptor, MVD and syndecan-1. Finally, our results showed that serum BAFF and APRIL levels could be useful biomarkers of MM disease activity and its progression which suggests that APRIL could be a possible novel therapeutic target in MM.
    Preview · Article · Oct 2013 · Annals of Hematology
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    ABSTRACT: Abstract The expression of adhesion molecules and other cell-surface molecules is substantial in the communication between plasma cells and bone marrow microenvironment, and may lead to increased proliferation of myeloma cells. Many of the cytokines involved in multiple myeloma (MM) pathogenesis, e.g. thrombopoietin (TPO) and interleukin-6 (IL-6), play a pivotal role in different developmental stages of megakaryocytopoiesis and thrombopoiesis. The principal aim of our study was to explore the relationship between thrombopoietic cytokines, megakaryocytes (MKs) and soluble P-selectin (sP-selectin) levels in MM patients before and after anti-angiogenic treatment. Forty-four patients (20 female and 24 male) with a newly diagnosed MM were examined in three groups, following a division based on the International Staging System, ISS. Plasma levels of TPO, IL-6 and soluble P-selectin (human sP-selectin) were measured by means of ELISA. Bone marrow specimens were studied to determine the number of MKs and the so-called "naked nuclei" (NN), as well as the expression of platelet-derived growth factor (PDGF). The comparison revealed a significantly higher concentration of cytokines and sP-selectin in newly diagnosed MM patients compared to healthy volunteers: for TPO, p = 0.01, IL-6, p = 0.0005 and sP-selectin, p = 0.00008, respectively. Marked differences were observed in the concentration of sP-selectin, expression of PDGF and MKs counts between patients with MM stage I and MM stage III. Statistically meaningful correspondences were also found between MKs versus TPO, NN versus TPO, as well as MKs versus MPV, p = 0.009, p = 0.004 and p = 0.0005, respectively. Furthermore, the analysis exhibited some statistically meaningful divergences between initial concentrations of sP-selectin in subgroups with different response after chemotherapy. The initial concentration of sP-selectin in the group of MM patients with complete or partial remission stood at 31.86 ± 6.13 ng/ml. In the remaining patients (stable disease), the concentration of sP-selectin amounted to 35.15 ± 7.23 ng/ml (p = 0.048). We found a correlation between sP-selectin and IL-6 (ρ = 0.57, p = 0.0004), TPO and IL-6 (ρ = 0.46, p = 0.001) as well as sP-selectin and TPO (ρ = 0.36, p = 0.043), and sP-selectin and PDGF (ρ = 0.36, p = 0.03). Our study has eventually demonstrated that sP-selectin, as a marker of platelet activation, could be a useful marker of maximum response to therapy. Its strong association with another marker like PDGF-AB could further lead to the development of new combinational therapeutic strategies of anti-angiogenic therapy in MM patients.
    No preview · Article · Jul 2013 · Platelets
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    ABSTRACT: B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and apoptosis inducing ligand (TRAIL) are members of the tumour necrosis factor (TNF) family. They are the main survival factors for immature, naive and activated B cells. We have analysed BAFF, APRIL and TRAIL serum concentrations in 52 patients with newly diagnosed IgG multiple myeloma and 20 healthy volunteers. The values were significantly higher in the studied patients and advanced diseases, decreasing after chemotherapy, compared to the control group. It was established that BAFF as APRIL (but not TRAIL) correlated with adverse prognostic factors such as IL-6 and lactate dehydrogenase. Furthermore, higher concentrations of APRIL and BAFF (but not TRAIL) predicted a shorter progression free survival, suggesting thereby an important prognostic marker and a possible therapeutic target in myeloma.
    No preview · Article · Jun 2013 · Leukemia research
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    ABSTRACT: Abstract Long-term outcomes following newer therapies for chronic lymphocytic leukemia (CLL) have rarely been reported. This paper presents the results of the final analysis of the Polish Adult Leukemia Group PALG-CLL2 study performed ten years from final patient enrollment. With the extended follow-up time, it was found that cladribine (2-CdA)-based combinations, CMC (2-CdA, cyclophosphamide, mitoxantrone) and CC (2-CdA, cyclophosphamide) administered as first-line treatment of progressive CLL result in significantly longer progression-free survival, but similar overall survival compared to 2-CdA monotherapy. Furthermore, the risk of potentially fatal late adverse events including infections, autoimmune complications and, particularly, secondary neoplasms is comparable among patients treated with CMC, CC or 2-CdA. The results of our analysis support the importance of long-term outcome monitoring of randomized trials in CLL.
    No preview · Article · May 2013 · Leukemia & lymphoma
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    ABSTRACT: Objectives: The relationship between treatments of chronic lymphocytic leukemia (CLL) with cladribine (2-CdA) or chlorambucil and immune thrombocytopenia (IT) has not been yet determined. Methods: The records of 777 patients in two randomized Polish Adult Leukemia Group (PALG)-CLL programs treated with these agents were retrospectively analyzed. Results: Immune thrombocytopenia occurred in 55 of 777 (7.1%) patients. No significant differences in IT prevalence were seen between patients on chlorambucil or 2-CdA-based regiments (P = 0.33). IT developed at a median time of 0.499 yr (0.06-4.8) from the start of CLL therapy. This time was significantly longer in patients treated with chlorambucil (2.03 yr, 95% CI: 0.06-4.22) in relation to patients treated with 2-CdA-based regiments (0.52 yr, 95%CI: 0.34-0.69, P = 0.049). Overall survival (OS) of patients with IT and those without IT were similar (2.65 yr vs. 3.2 yr P = 0.23) but the severity of bleeding was more pronounced in the 2-CdA group. The responses to IT therapy were 35%, 54% and 75% for steroids, chemotherapy and splenectomy, respectively. Conclusions: In this study, an unexpectedly high percentage of IT incidence was demonstrated in patients with CLL requiring chemotherapy. Although no marked differences were seen in IT frequency in patients treated with 2-CdA-based regiments compared to chlorambucil regimen, the clinical course of hemorrhagic diathesis was more severe in 2-CdA group. Also, the time elapsed from study screening to IT diagnosis was significantly shorter in the 2-CdA group than in the chlorambucil group suggesting a causative relationship. The appearance of IT did not influence the median time of OS.
    No preview · Article · Mar 2013 · European Journal Of Haematology
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    ABSTRACT: The potential role of alterations in protein Z (PZ) concentrations in the pathogenesis of coagulation has been investigated in several studies which, however, yielded conflicting results. Protein Z deficiency may induce bleeding as well as prothrombotic tendencies and it might occur as an inherited disorder. The principal aim of the present study was to explore the concentration of protein Z and protein Z-dependent protease inhibitor (ZPI) in patients with haemophilia A. In haemophilia A patients mean plasma concentrations of PZ and ZPI were significantly higher than in healthy individuals: PZ (1.87±0.68μg/mL vs 1.49±0.54μg/mL) and ZPI (5.02±1.11μg/mL vs 4.22±0.55μg/mL), with p=0.02 and p=0.03, respectively. In the subgroup with severe haemophilia A, an in-depth analysis revealed a tendency to modulating effect of the PZ (r=-0.53; p=0.072) and a statistically significant one in the case of ZPI (rho=-0.79, p=0.002) on the bleeding rate. It simultaneously disclosed a statistically significant correlation between the number of bleeds to the joints (20.18±14.1), PZ (r=-0.72; p=0.04) and ZPI (rho=-0.88, p=0.001). With reference to this particular group of patients, the study also showed some other statistically meaningful correspondences: between PZ and ZPI (rho=0.65, p=0.02), PZ and FIX (r=-0.61, p=0.04), as well as ZPI and FVIII (rho=0.78, p=0.002). In conclusion, despite the fact that FVIII deficiency is undoubtedly the main mechanism of bleeding in haemophilia A patients, the activity of PZ/ZPI complex may play some modulating role in the matter.
    No preview · Article · Dec 2012 · Thrombosis Research
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    Jaroslaw Piszcz · Lukasz Bolkun · Edyta Cichocka · Janusz Kloczko
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    ABSTRACT: Secondary acute leukaemia (s-ALL) is a destructive complication in patients who have been previously treated for other cancer. Secondary acute lymphoblastic leukaemia is rarely reported whereas secondary acute myeloid leukaemia is much more common. Chromosomal 11q23 abnormality, frequently detected in therapy-related acute myeloid leukaemia, is the most common cytogenetic alteration in secondary ALL too. However, s-ALL cases without 11q23 abnormality have rarely been described. Furthermore, there are only a few published medical reports describing occurrence of acute lymphoblastic leukaemia in multiple myeloma (MM) patients. We would like to present our experience with a patient with MM, who developed ALL without 11q23 abnormality, nine years after alkylating-agent containing treatment. The course of the disease was complicated by thrombosis that obstructed the possibility of effective treatment. In conclusion, it should be kept in mind that the development of a more aggressive neoplasm related to chemotherapy treatment as well as the inherent genetic instability of normal and abnormal lymphoid progenitors may affect overall survival of an indolent lymphoma patient.
    Preview · Article · Dec 2012 · Contemporary Oncology / Wspólczesna Onkologia
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    ABSTRACT: Purpose: Angiogenesis appears to be a prominent feature of many hematological disorders, particularly in multiple myeloma (MM). Progression in MM also involves secretion of the metaloproteinases (MMPs). In this study, the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and its receptor, in bone marrow trephine biopsy (TB) of thirty six MM patients before and after the treatment or during progression was examined. The MMP-2 secretion was assessed from the same patients. Material/methods: Immunohistochemical staining of bone marrow specimens for angiogenic factors and microvessel density (MVD) and bone marrow aspirates for Western blot analysis of MMP-2 expression was performed. Results: In active, untreated MM patients, we found statistically significant differences in the expression of angiogenic factors according to the patients after the anti-angiogenic treatment. We found statistical differences of the expression of angiogenic factors between the group of patients with a response after the treatment and the patients who had progression during the treatment. The data showed statistically significant decreased MVD after the treatment. The results showed statistically significant differences between initial secretion of MMP-2 in active, untreated MM patients and patients with a response after the treatment and patients with progression during the treatment. Conclusions: We showed that not only decreased expression of angiogenic cytokines is present after the anti-angiogenic treatment but also activity of MMP-2 in MM patients who responded to the treatment. Combination therapy with the inhibition of the activity of MMPs could represent an interesting therapeutical approach in MM.
    No preview · Article · Oct 2012 · Advances in Medical Sciences

Publication Stats

1k Citations
261.91 Total Impact Points

Institutions

  • 2015
    • Silesian University of Technology
      Gleiwitz, Silesian Voivodeship, Poland
  • 2003-2015
    • Medical University of Bialystok
      • Department of Haematology
      Belostok, Podlasie, Poland
  • 2007
    • Medical University of Lublin
      • Department Hemato-Oncology and Bone Marrow Transplantation
      Lyublin, Lublin Voivodeship, Poland
  • 2006
    • University of Lodz
      • Department of Cytobiochemistry
      Łódź, Łódź Voivodeship, Poland
  • 2004
    • University of Bialystok
      Belostok, Podlasie, Poland