Sławomira Kyrcz-Krzemień

Medical University of Silesia in Katowice, Catowice, Silesian Voivodeship, Poland

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Publications (55)109.5 Total impact

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    ABSTRACT: Imatinib mesylate (IM) remains the treatment of choice for chronic myeloid leukemia (CML) showing a remarkable efficacy and offers a perspective for long disease-free survival. Due to prolonged administration of IM, the questions about the possible impact on the development of secondary malignancies (SM) are raised. To investigate the incidence and clinical outcome of secondary malignancies during IM therapy for CML. The records of 221 CML patients treated with IM between 2003-2013 in a single institution were reviewed. The Poisson regression model was used to estimate the relative risks for SM and death in CML patients. Secondary malignancies developed in eight out of the 221 patients (3.6%) receiving IM for a median of 61 months (range, 10-137 months). Female/male ratio was 5/3. Two patients were diagnosed with their CML at accelerated phase whereas 6 had chronic phase. The median age at IM initiation was 58 years (range, 31-72 years). Five of these 8 SM patients received IM after other treatments failure: interferon α (n=5), hydroxyurea (n=4) and cytarabine (n=1). Three patients received IM as a frontline therapy. All patients were on IM at 400mg daily at SM occurrence. The therapy for SM included surgery (n=3), chemotherapy only (n=3), and chemotherapy followed by radiotherapy (n=1). One patient did not receive treatment due to disseminated disease. All CML patients were in hematologic and complete cytogenetic response (CCR) at the time of SM development. All of them also met the criteria for major molecular response (BCR-ABL(IS) ≤0.1%). They continued their IM while receiving treatment for SM. Among eight patients with SM, five patients are alive and remain in CCR on IM whereas three patients died due to SM. The risks for SM development as well as death due to SM in CML patients were not statistically increased if compared to age-adjusted population. The association between IM therapy for CML and SM development has not been found.
    Mediterranean Journal of Hematology and Infectious Diseases 12/2015; 7(1):e2015003. DOI:10.4084/MJHID.2015.003
  • Polskie archiwum medycyny wewnȩtrznej 07/2015; · 2.05 Impact Factor
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    ABSTRACT: The present study aimed to assess the impact of the CXCL12 gene polymorphism (rs1801157) on clinical outcome of hematopoietic stem cell transplantation from unrelated donors. Toxic complications were less frequent among patients transplanted from donors carrying the CXCL12-3'-A allele (42/79 vs. 105/151, p=0.014 and 24/79 vs. 73/151, p=0.009, for grade II-IV and III-IV, respectively). Logistic regression analyses confirmed a role of donor A allele (OR=0.509, p=0.022 and OR=0.473, p=0.013 for grade II-IV and III-IV toxicity). In addition, age of recipients (OR=0.980, p=0.036 and OR=0.981, p=0.040, respectively) was independently protective while female to male transplantation and HLA compatibility were not significant. The incidence of aGvHD (grades I-IV) was lower in patients having A allele (52/119 vs. 113/204, p=0.043) and AA homozygous genotype (6/25 vs. 159/298, p=0.005). Independent associations of both genetic markers with a decreased risk of aGvHD were also seen in multivariate analyses (A allele: OR=0.591, p=0.030; AA homozygosity: OR=0.257, p=0.006) in which HLA compatibility seemed to play less protective role (p<0.1) while recipient age and donor-recipient gender relation were not significant. Moreover, CXCL12-3'-A-positive patients were less prone to early HHV-6 reactivation (2/34 vs. 19/69, p=0.026). The presence of the CXCL12-3'-A variant was found to facilitate outcome of unrelated HSCT. Copyright © 2015. Published by Elsevier Ltd.
    Cytokine 05/2015; DOI:10.1016/j.cyto.2015.05.001 · 2.87 Impact Factor
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    Małgorzata Krawczyk-Kuliś · Sławomira Kyrcz-Krzemień
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    ABSTRACT: Currently, infiltration of the central nervous system (CNS) in lymphoma patients is an unfavorable prognostic factor contributing to shorter survival. In these cases, immunophenotypisation has become important for evaluation of cerebrospinal fluid cells – especially in the so-called “subclinical form of CNS involvement.” Other methods used in these cases include diagnostic imaging and cytological examination. Therapy protocols, including the prophylactic intrathecal administration of drugs, are used for treatment of some lymphoma subtypes characterized by frequent CNS infiltrations, either at diagnosis or during relapse (lymphoblastic lymphoma/acute lymphoblastic leukemia, Burkitt's lymphoma, diffuse large B cell lymphoma, and lymphoma in HIV+ patients). In current clinical practice, prophylactic irradiation of the CNS is used less frequently. In addition to local treatment of the CNS, systemic therapy with high-dose methotrexate and cytosine arabinoside is recommended. The intrathecal treatment of choice is liposomal cytosine arabinoside or triple therapy: methotrexate, cytarabine, and dexamethasone. Because liposomal cytosine arabinoside has sustained activity in the CSF for 2 weeks, the number of intrathecal administrations necessary to eradicate CNS infiltrations may be reduced.
    Acta haematologica Polonica 03/2015; 46(1):20-27. DOI:10.1016/j.achaem.2014.11.003
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    ABSTRACT: The main barrier to successful haematopoietic stem cell transplantation (HSCT) is the development of post-transplant complications. Although human leucocyte antigen (HLA)-matching is critical in both HLA-matched familial and matched unrelated donor transplants to deter acute graft-versus-host disease (aGvHD) and rejection, recently functional non-HLA immune associated genes have also been considered in attempts to evaluate their potential prediction values and uncover novel factors that may optimize donor selection processes. Mutations and polymorphisms within these non-HLA encoded genes affect, for example, the amount of cytokine/chemokine produced in response to allo-antigen or infection. Knowledge of both patient and donor non-HLA genotype may therefore aid the development of new preventative and therapeutic strategies by taking the degree of ‘risk-associated’ genotype into account. The results of our present work contribute to these studies and strongly suggest that the 32-nucleotide deletion within the CCR5 gene (CCR5Δ32 polymorphism; rs333) is of prognostic value for the outcome of HSCT from unrelated donors.
    British Journal of Haematology 03/2015; DOI:10.1111/bjh.13387 · 4.96 Impact Factor
  • Grzegorz Helbig · Sławomira Kyrcz-Krzemień
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    ABSTRACT: Hypereosinophilic syndrome (HES) is a group of rare disorders characterized by marked and persistent blood hypereosinophilia and documented as eosinophilia-attributable organ impairment. Discovery of some novel genetic abnormalities let to the categorization of HES patients into a common group of myeloid and lymphoid neoplasms with eosinophilia and recurrent gene rearrangements: platelet-derived growth factor receptor α and β (PDGFRA/B) and fibroblast growth factor receptor 1 (FGFR1). This classification, however, differs from that one proposed by Working Group for Eosinophilic Disorders in 2012. Namely, HES patients were divided into 3 variants: idiopathic, myeloproliferative (including cases with well-known gene rearrangements) and reactive (including lymphocytic HES). Despite the progress in diagnostic approach, especially in molecular testing, a vast majority of HES cases remain idiopathic. Except the PDGFRA/B- positive patients where tyrosine kinase inhibitor – imatinib mesylate – remains a treatment of choice, the therapy for other HES variants is somehow similar and includes steroids, hydroxyurea and interferon. The PDGFRA/B-positive population has an excellent prognosis with complete hematologic and molecular remissions achieved as 100% and >95% in imatinib-treated patients, respectively. The estimated probability of survival at 20 years for strictly defined idiopathic HES is found to be around 70%. The worst prognosis was demonstrated for cases with chronic eosinophilic leukemia – not otherwise specified and those with FGFR1 rearrangements. This review presents the current state of knowledge on definitions, classifications and treatment of HES in the molecular era.
    Acta haematologica Polonica 02/2015; 46(2). DOI:10.1016/j.achaem.2015.02.006
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    ABSTRACT: Fungal colonization and infections remain a major cause of infection morbidity and mortality following hematopoietic stem cell transplantation (HSCT) in patients with hematological malignancies. The aim of this study was to analyze the spectrum of fungal microflora of the respiratory tract (oral cavity, pharynx, epiglottis, and sputum) in patients undergoing HSCT and to evaluate the relationship between HSCT type and incidence of mycotic colonization and infections. Retrospective analysis of fungal isolates collected from the respiratory tract (oral cavity, pharynx, epiglottis, and sputum) of 573 patients undergoing HSCT was performed. The overall rate of fungal colonization in patients undergoing HSCT was 8.7%. Patients undergoing allogeneic HSCT were statistically significantly more often colonized (12.95%) compared to autologous HSCT recipients (4.7%). Colonizing cultures were mainly C. albicans and C. krusei, and sporadically C. glabrata, C. famata, Aspergillus spp. and Saccharomyces cerevisiae. C. albicans was the most frequent species found in isolates from the pharynx, sputum, and oral cavity collected from patients undergoing HSCT. Aspergillosis was more common after allogeneic than after autologous HSCT. The pharynx was the most frequently colonized site. Allogeneic HSCT recipients are more susceptible to fungal infections compared to the autologous group. Selection of species during prophylaxis and antifungal therapy requires developing more effective prevention and treatment strategies based on new antifungal drugs and microbe-specific diagnoses.
    Medical science monitor: international medical journal of experimental and clinical research 01/2015; 2015(21). DOI:10.12659/MSM.893267 · 1.22 Impact Factor
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    ABSTRACT: Some cancers treated with allogeneic hematopoietic stem-cell transplantation (HSCT) are sensitive to natural killer cell (NK) reactivity. NK function depends on activating and inhibitory receptors and is modified by NK education/licensing effect, mediated by coexpression of inhibitory killer-cell immunoglobulin-like receptor (iKIR) and its corresponding HLA I ligand. We assessed activating (a)KIR-based HLA I-dependent education capacity in donor NKs in 285 patients with hematological malignancies after HSCT from unrelated donors. We found significantly adverse progression free survival (PFS) and time to progression (TTP) in patients who received transplant from donors with NKs educated by C1:KIR2DS2/3, C2:KIR2DS1 or Bw4:KIR3DS1 pairs (for PFS, HR=1.70, P=0.0020,Pcorr=0.0039; HR=1.54, P=0.020,Pcorr=0.039 and HR=1.51, P=0.020,Pcorr=0.040; and for TTP, HR=1.82, P=0.049,Pcorr=0.096; HR=1.72, P=0.096,Pcorr=0.18 and HR=1.65, P=0.11,Pcorr=0.20, respectively). Reduced PFS and TTP was significantly dependent on the number of aKIR-based education systems in donor (HR=1.36, P=0.00031,Pcorr=0.00062 and HR=1.43, P=0.019,Pcorr=0.038). Furthermore, the PFS and TTP were strongly adverse in patients with missing HLA ligand cognate with educating aKIR in donor (HR=3.25, P=0.00022,Pcorr=0.00045 and HR=3.82, P=0.027,Pcorr=0.054). Together, these data suggest important qualitative and quantitative role of donor NK education via aKIR-cognate HLA ligand pairs in the outcome of HSCT. Avoiding the selection of transplant donors with high number of aKIR-based education systems, especially those with missing cognate ligand in recipient is advisable. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2015; 21(5). DOI:10.1016/j.bbmt.2015.01.018 · 3.35 Impact Factor
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    ABSTRACT: Primary mediastinal B-cell lymphoma (PMBCL) is an aggressive distinct subtype of diffuse large B-cell lymphoma (DLBCL). There is no standard treatment for PMBCL and the value of mediastinal radiotherapy and autologous hematopoietic stem cell transplantation (AHSCT) remains to be elucidated.
    Acta haematologica Polonica 12/2014; 11(1). DOI:10.1016/j.achaem.2014.12.002
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    ABSTRACT: Donor lineage-specific chimerism of hematopoietic cells enables very precise monitoring of engraftment in selected cell lines after allogeneic stem cell transplantation (allo-SCT).Materials and methodsThe study group consisted of 12 acute leukemia patients who underwent allo-SCT in the Department of Hematology and Bone Marrow Transplantation in Katowice, Poland. Lineage-specific chimerism was assessed in B cells (CD19+ CD38−/+), plasma cells (CD19+ CD38++), T cells (CD3+ or CD7+ CD56−), monocytes (CD14+), and immature progenitor cells deriving from myeloid line (CD34+CD19). We also assessed erythrocyte chimerism by flow cytometry.ResultsAll patients engrafted. 8 out of 10 patients presented normal donor hematopoiesis. Lineage specific chimerism in these patients corresponded with chimerism analysis in unsorted material and with undetectable minimal residual disease (MRD). Relapse of the underlying disease was diagnosed in 2 patients. In both cases loss of donor chimerism occurred in leukemia specific cell line and corresponded with detectable MRD. One patient with secondary graft failure presented decreasing lineage specific chimerism in all subpopulations, with negative MRD status. In 10 patients normal hematopoiesis of donor-origin was assessed by flow cytometry. In one case no donor-derived erythrocytes were detected and the diagnosis of pure red cell aplasia was set.Conclusions Lineage specific chimerism as a method of high sensitivity and specificity allows for precise assessment of donor chimerism especially in clinically ambiguous situations. Assessment of erythrocyte chimerism by flow cytometry is a reliable method of monitoring erythroblastic line engraftment. Presented results are preliminary and the study is being continued.
    Acta haematologica Polonica 11/2014; 45(4). DOI:10.1016/j.achaem.2014.10.005
  • Polskie archiwum medycyny wewnȩtrznej 09/2014; 124(11). · 2.05 Impact Factor
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    ABSTRACT: Dipeptidyl peptidase IV is a membrane enzyme involved in intracellular interactions governing processes. Proven its effects on engraftment the transplanted allogeneic hematopoietic cells. The aim of this study was to analyze the expression of CD26 in the mobilization of hematopoietic cells for auto-transplantation in multiple myeloma patients. In 30 patients, who, during the 2011–2012, underwent the mobilization of hematopoietic cells, CD26 was determined on CD34 positive cells as well as on lymphocytes, monocytes and granulocytes, before mobilization procedures, as well as on the cells obtained after separation on cell separator. We found a statistically significant increase in the number of mononuclear cells expressing CD26, non-expression of CD26 on granulocytes, both before and during the mobilization procedures. Additionally we found a week expression of CD26 on CD34 positive cells. The obtained results seem to indicate an important role of bone matrix cells expressing CD26 in the process of mobilization of hematopoietic cells in myeloma multiplex patients.
    Acta haematologica Polonica 07/2014; DOI:10.1016/j.achaem.2014.01.003
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    ABSTRACT: NK cells are involved in clearance of cancer cells via natural cytotoxicity. Inhibitory killer cell immunoglobulin-like receptors (iKIRs) function as a protective mechanism for normal autologous cells provided iKIR engagement by self HLA class I cognate ligands. iKIR-Ligand mismatch between hematopoietic stem cell transplant (HSCT) donor and recipient was shown to trigger graft versus leukemia effect in acute myeloid leukemia (AML) patients. Our objective was to examine the clinical effect of donor-recipient iKIR-ligand mismatch in patients with different kinds of neoplasia. In 278 patients with lympho- or myeloproliferative diseases and their HSCT donors HLA class I genes at high resolution were typed and 4 groups of iKIR ligands (C1,C2,ABw4,A3/11) were determined. Clinical records were retrospectively collected according to EBMT guidelines. Patients’ diagnosis included: AML 131(47%), ALL 69(25%), CML/CLL 56(20%), lymphoma/myeloma 16(6%) and other neoplasia 6(2%). We found significantly increased risk of death (reduced overall survival, OS) after HSCT in neoplastic patients who were transplanted from iKIR-ligand mismatched donors as compared with non iKIR-ligand mismatched pairs (60.7% vs. 39.6%; HR=1.72; 95%CI 1.02-2.87; P=0,040; median time to death 314 vs. 362 days (d)). Unexpectedly, we found remarkably reduced OS if iKIR-ligand mismatch was of GvH direction (84.6% vs. 39.6%;HR=3.24; P=0.00021; 91 vs. 367 d). In these cases the progression free survival (PFS) was reduced even further (92.3% vs. 47.5%; HR=3.74; P=0.000016; median time to event 75 vs. 348 d) and the time to progression (TTP) was highly reduced too (27.3% vs. 17.7%; HR=4.35; P=0.015; 72 vs. 348.5 d). Opposite direction of iKIR-ligand mismatch (HvG) implicated a weak trend toward improved OS (25.0% vs. 42.5%; HR=0.49; P=0.23; 618.5 vs. 355 d). Acute GvHD incidence remained similar in compared groups (61.5% vs. 53.2%; HR=1.41; P=0.56). In HSCT from iKIR-ligand mismatched donors of GvH direction the survival of patients with neoplastic diseases was dramatically reduced due to increased progression of the disease. These results suggest avoidance of iKIR-ligand mismatches of GvH direction in HSC donors selected for patients with neoplastic diseases. Supported by the National Centre for Research and Development grant N R13 0082 06.
    28th European Immunogenetics and Histocompatibility Conference, EFI 2014, , 25-28.06.2014., Stockholm, Sweden; 06/2014
  • Grzegorz Helbig · Karolina Torba · Jacek Pająk · Sławomira Kyrcz-Krzemień
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    ABSTRACT: Mastocytosis is a group of rare disorders with variable phenotypes caused by the presence of excessive number of mast cells (mastocytes) and CD34+ mast cell precursors. In systemic mastocytosis different tissues/organs may be involved including the skin, bone marrow, liver, spleen, lymph nodes or bowel. Due to clinical activity three types of systemic mastocytosis may be distinguished i.e., indolent, smoldering and aggressive mastocytosis. In this case report we present a 67-year-old patient with aggressive systemic mastocytosis who was hospitalized for splenomegaly and cholestatic liver disease.
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    ABSTRACT: Mastocytosis is a group of rare disorders with variable phenotypes caused by the presence of excessive number of mast cells (mastocytes) and CD34+ mast cell precursors. In systemic mastocytosis different tissues/organs may be involved including the skin, bone marrow, liver, spleen, lymph nodes or bowel. Due to clinical activity three types of systemic mastocytosis may be distinguished i.e., indolent, smoldering and aggressive mastocytosis. In this case report we present a 67-year-old patient with aggressive systemic mastocytosis who was hospitalized for splenomegaly and cholestatic liver disease.
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    ABSTRACT: Carfilzomib (CFZ), an epoxyketone with specific chymotrypsin-like activity, is a second-generation proteasome inhibitor with significant activity in patients with relapsed and refractory multiple myeloma. On July 20, 2012, the US Food and Drug Administration approved CFZ to treat patients with multiple myeloma who have received at least two prior therapies including bortezomib (BORT) and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy. Cytogenetic abnormalities did not appear to have a significant impact on the CFZ activity. Carfilzomib was well tolerated and demonstrated promising efficacy in patients with renal insufficiency. Pomalidomide (POM) (CC-4047) is a novel immunomodulatory derivative (IMID) with a stronger in vitro anti-myeloma effect compared with "older" IMIDs - thalidomide and lenalidomide (LEN). On February 8, 2013, the US Food and Drug Administration approved POM (Pomalyst, Celgene) for the treatment of MM patients who have received at least two prior therapies including LEN and BORT and have demonstrated progression on or within 60 days of completion of the last therapy. Pomalidomide is a novel IMID with significant anti-myeloma activity and manageable toxicity. This compound has shown high efficacy in MM patients who were resistant to prior use of LEN/BORT as well as in patients with a high-risk cytogenetic profile. Carfilzomib and POM have very high efficacy and will be used also in first line therapy in future.
    Contemporary Oncology / Wspólczesna Onkologia 01/2014; 18(1):17-21. DOI:10.5114/wo.2014.40175 · 0.22 Impact Factor
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    ABSTRACT: Background/Aim: In this study, we carried out a retrospective analysis of the efficacy and toxicity of bendamustine in patients with B-cell lymphoproliferative diseases. Methods: Bendamustine was administered both as monotherapy and in combined protocols to 92 patients, including 76 patients with chronic lymphocytic leukemia (CLL) and 16 patients with indolent lymphomas. Bendamustine plus rituximab was used to treat 65.2% of the patients, and 34.8% of the patients received bendamustine as monotherapy. Results: The overall response rate was 64.2%, including the complete response rate (18.5%) and the partial response rate (45.7%). The median overall survival (OS) was 11.5 months. Among the pretreatment parameters, β2-microglobulin (RR = 1.413; p = 0.001) and hemoglobin levels (RR = 0.85; p = 0.03) significantly influenced survival. The OS was significantly longer in patients who received ≤2 lines of previous therapy compared to >3 lines (p = 0.043; log-rank test) and those who received ≥4 courses of therapy with bendamustine (p = 0.0007; log-rank test). Toxicity was predominantly hematological, including grade III/IV neutropenia in 33.7%, thrombocytopenia in 13%, and anemia in 13% of patients. Conclusion: Bendamustine, both in monotherapy and in combination regimens, is an effective therapy with a favorable toxicity profile in patients with indolent B-cell malignancies. © 2014 S. Karger AG, Basel.
    Chemotherapy 01/2014; 59(4):280-289. DOI:10.1159/000357468 · 1.55 Impact Factor
  • Grzegorz Helbig · Sławomira Kyrcz-Krzemień
    The Journal of allergy and clinical immunology 01/2014; 133(3). DOI:10.1016/j.jaci.2013.12.023 · 11.25 Impact Factor
  • Grzegorz Helbig · Sławomira Kyrcz-Krzemień
    American Journal of Hematology 01/2014; 89(1). DOI:10.1002/ajh.23588 · 3.48 Impact Factor

Publication Stats

134 Citations
109.50 Total Impact Points

Institutions

  • 2008–2015
    • Medical University of Silesia in Katowice
      • Department of Haematology and Bone Marrow Transplantation
      Catowice, Silesian Voivodeship, Poland
    • Silesian University of Technology
      Gleiwitz, Silesian Voivodeship, Poland
  • 2012
    • Pomorski Uniwersytet Medyczny
      Stettin, West Pomeranian Voivodeship, Poland