Publications by authors named "Katerina Steinerova"

9 Publications

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Allogeneic Stem Cell Transplantation in Patients With FLT3-ITD Mutated AML: Transplantation in CR1 Is the Decisive Factor for Good Outcome.

Clin Lymphoma Myeloma Leuk 2019 07 19;19(7):462-469. Epub 2019 Apr 19.

Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.

Background: Patients with internal tandem duplication in fms-related tyrosine kinase receptor gene 3 (FLT3-ITD)-mutated acute myeloid leukemia (AML) have a dismal prognosis and the only curative option seems to be allogeneic stem cell transplantation (alloSCT). However, its timing is still matter of debate.

Patients And Methods: We retrospectively analyzed 73 consecutive AML patients with FLT3-ITD (median age 53, range 20-68 years) allografted with consistent policy to try to refer them all for upfront alloSCT in first complete remission (CR1).

Results: With a median follow-up of 44 (range, 5-135) months the 5-year overall survival (OS)/disease-free survival (DFS) probabilities were 49%/47%. The cumulative incidence of relapse and nonrelapse mortality (NRM) were 37% and 14%, respectively. The estimated 5-year OS for patients who received transplantation in CR1 was 62% versus 0% for patients who received transplantation beyond CR1. Multivariable analysis identified stem cell transplantation beyond CR1 as the key factor for poor OS (hazard ratio [HR], 5.41; P < .0001), DFS (HR, 4.41; P = .0002), and high relapse incidence (HR, 8.08; P < .0001). Acute graft versus host disease Grade ≥3 predicted higher NRM (HR, 3.80; P = .059) as well as inferior OS (HR, 2.04; P = .0079). No association of patient age, nucleophosmin status, donor type, conditioning, and other variables on the survival was detected.

Conclusion: AlloSCT should be regarded with urgency as soon as CR1 is achieved in this subset of AML patients.
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http://dx.doi.org/10.1016/j.clml.2019.04.005DOI Listing
July 2019

First-line imatinib in elderly patients with chronic myeloid leukaemia from the CAMELIA registry: Age and dose still matter.

Leuk Res 2019 06 24;81:67-74. Epub 2019 Apr 24.

Department of Haemato- Oncology, Faculty Hospital and Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.

We retrospectively evaluated the role of age and dosage in 372 CML patients (170 women, 202 men) treated with first-line imatinib (IMA) from the records of the CAMELIA registry. The median follow-up of the patients was 82.3 (18.0-177.3) months. The treatment results of 80 elderly patients aged over 65 years at diagnosis were compared in analysis "A" with those of 292 younger patients and in analysis "B" with those of 90 patients younger than 40 and 202 patients aged 40-64. The elderly patients had statistically adverse values of the Sokal, ELTS, and ECOG scores and Charlson comorbidity index in both analyses (p from = 0.012 to ≤ 0.001). Despite a more frequent use of a daily dose lower than 400 mg - in 31 elderly patients (38.8%) than in 45 younger ones (15.4%) (p < 0.001), there were no statistically significant differences in the achievement of optimal haematological, cytogenetic, and molecular responses according to the ELN criteria in both the analyses, A and B. The comparisons of overall survival with CML-related death (OS) and event-free survival (EFS) were insignificant inanalysis A (p = 0.07 and 0.396, respectively) but progression-free survival (PFS) differed significantly (p = 0.007). In analysis B OS and PFS differed significantly (p = 0.027 and 0.003) but EFS was similar (p = 0.351). Elderly patients with a sustained dose of IMA of 400 mg/day have insignificantly better OS, PFS, and EFS compared to patients treated with a lower dosage of IMA. The results in the treatment of the elderly CML patients were comparable with those of the younger ones in terms of the probabilities of the achievement of optimal ELN responses. However, the results for the survival probabilities were influenced by age and the IMA dosage.
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http://dx.doi.org/10.1016/j.leukres.2019.04.011DOI Listing
June 2019

Pre-transplant Quantitative Determination of NPM1 Mutation Significantly Predicts Outcome of AIlogeneic Hematopoietic Stem Cell Transplantation in Patients with Normal Karyotype AML in Complete Remission.

Anticancer Res 2016 10;36(10):5487-5498

Biomedical Center, Faculty of Medicine in Plzen, Charles University Prague, Plzen, Czech Republic.

Background/aim: Minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) before allogeneic hematopoietic stem cell transplantation (alloHSCT) can influence the results of therapy. With the aim of evaluating the potential role of pre-transplant MRD, we studied the impact of pre-transplant MRD level on the outcome of alloHSCT in patients with AML in complete remission (CR).

Patients And Methods: From 2/2005 to 9/2014, 60 patients with a median age of 54 years (range=30-66 years) with normal karyotype-AML harboring nucleophosmin 1 (NPM1) mutation [53% Fms-related tyrosine kinase receptor 3 internal tandem duplication (FLT3/ITD)-positive] in first (n=45) or second (n=15) CR underwent myeloablative (n=16) or reduced-intensity (n=44) alloHSCT (27% related, 73% unrelated). The MRD level was determined from bone marrow samples using real-time polymerase chain reaction for detection of NPM1 mutations before starting the conditioning regimen.

Results: The estimated probabilities of 3-year relapse, event-free survival (EFS) and overall survival (OS) for the whole cohort were 28%, 54%, and 59%, respectively. Statistical analysis showed that only age over 63 years and high MRD level affected alloHSCT outcome. Pre-transplant MRD level of 10 mutant copies of NPM1 per 10,000 Abelson murine leukemia viral oncogene homolog 1 (ABL) copies had the strongest statistical significance, and detection of higher MRD level (>10 NPM1-mutant copies) before alloHSCT was associated with increased overall mortality (hazard ratio=3.71; 95% confidence interval=1.55-9.06; p=0.004). The estimated probabilities of 3-year relapse, EFS, and OS were 6%, 72%, and 75% for patients with a low level of MRD and 48%, 35%, and 40% for patients with a higher level.

Conclusion: Our data showed that the pre-transplant level of MRD in patients with normal karyotype AML harboring NPM1 mutation in CR provides important prognostic information, which as an independent prognostic factor predicts transplant results.
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http://dx.doi.org/10.21873/anticanres.11130DOI Listing
October 2016

Evaluation of 5-year imatinib treatment of 458 patients with CP-CML in routine clinical practice and prognostic impact of different BCR-ABL cutoff levels.

Cancer Med 2013 Apr 21;2(2):216-25. Epub 2013 Feb 21.

Institute of Hematology and Blood Transfusion Prague, Czech Republic.

We evaluated responses to the treatment and long-term outcomes of chronic myeloid leukemia patients treated with imatinib as first-line treatment in routine clinical setting from two countries with centralized tyrosine kinase inhibitors (TKIs) treatment. We assessed prognostic significance of European LeukemiaNet (ELN) 2006- and 2009-defined responses and the prognostic value of molecular responses at defined time points on 5-year survivals. Among the cumulative rates of incidence of hematologic, cytogenetic, and molecular responses and all important survival parameters, we evaluated the prognostic significance of different BCR-ABL transcript-level ratios (≤1%; >1%-≤10%; >10%) at 3, 6, 12, and 18 months (n = 199). The ELN optimal response criteria and their predictive role were significantly beneficial for event-free survival at all given time points. We found significant improvement in survivals of patients with BCR-ABL lower than 10% in the 6th and 12th months. Significantly better outcome was found in patients who achieved major molecular response (MMR) in the 12th month. The cumulative incidences of complete cytogenetic response (CCyR) and MMR were significantly associated with the molecular response in the 3rd month. The ELN response criteria and their predictive role were helpful at given time points; however, the 2009 definition did not significantly alter the prognostic accuracy compared with that of the 2006 definition. The significant value was observed for cytogenetic responses at the 6th and 12th month. Moreover, progression-free and event-free survivals were improved with MMR at the 12th month.
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http://dx.doi.org/10.1002/cam4.59DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639660PMC
April 2013

The effect of polyvinylpyrrolidone-sodium hyaluronate gel (Gelclair) on oral microbial colonization and pain control compared with other rinsing solutions in patients with oral mucositis after allogeneic stem cells transplantation.

Med Sci Monit 2011 Oct;17(10):CR572-6

Department of Haemato-Oncology, University Hospital in Pilsen, Pilsen, Czech Republic.

Background: Gelclair is an oral lubricating gel used in the management of oral mucositis (OM). We evaluated its efficacy, tolerance and impact on oral cavity microbial colonization in patients with OM after allogeneic hematopoietic stem cells transplantation.

Material/method: Gelclair was administered in a group of 22 patients with active OM. A control group of 15 patients used other rinsing solutions (chlorhexidine, benzydamine, salvia). Tests with oral cavity swabs for microbiology analysis were performed once a week.

Results: The characteristics of OM in both groups were comparable, and rinsing solutions had satisfactory tolerability. There was no difference in the median improvement of oral intake and OM-related pain relief, which was assessed mostly as "slight effect". In the Gelclair group, the effect duration was longer (median 3 [0-5] vs. 1 [0-3] hours, p = 0.001). There was significant increase of Enterococcus faecalis and Candida sp. colonization of the oral cavity over the course of the hospitalization and significantly reduced incidence of such colonization in patients with OM in the Gelclair group: 1/22 (5%) vs. 6/15 (40%), p = 0.01. In vitro tests showed inhibited growth of Enterococcus faecalis and Candida sp. colonies within the area of the Gelclair application.

Conclusions: Gelclair may be individually helpful in the management of OM and pain in patients after allogeneic stem cells transplantation. Its use did not lead to worsened oral bacterial and yeast colonization and probably even helped to protect mucosa from Enterococcus and Candida sp. Further studies based on larger cohorts are needed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539478PMC
http://dx.doi.org/10.12659/msm.881983DOI Listing
October 2011

Pre-transplant positron emission tomography in patients with relapsed Hodgkin lymphoma.

Leuk Lymphoma 2011 Sep 23;52(9):1668-74. Epub 2011 Jun 23.

Department of Clinical Hematology, Charles University Hospital Kralovske Vinohrady, Prague, Czech Republic.

This retrospective study evaluated the secondary clinical risk score at relapse, the prognostic significance of pre-transplant positron emission tomography (PET), and complete remission (CR) assessed by computed tomography (CT) after salvage chemotherapy before autologous stem cell transplant (ASCT) in 76 patients with relapsed/refractory Hodgkin lymphoma (HL). Median follow-up after ASCT was 23 months. Overall 11/20 PET-positive and 14/56 PET-negative patients relapsed after ASCT. In univariate analysis, only PET negativity before ASCT was significantly associated with better 2-year progression-free survival (PFS) (72.7 ± 6.3% vs. 36.1 ± 11.6%, p = 0.01) and 2-year overall survival (OS) (90.3 ± 4.1% vs. 61.4 ± 11.6%, p = 0.009). Other factors were not significant. In multivariate analysis, none of the evaluated factors were significant for PFS and OS. However, positive pre-transplant PET identified a population with worse PFS and OS at least in univariate analysis.
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http://dx.doi.org/10.3109/10428194.2011.573889DOI Listing
September 2011

Retrospective survey on the prevalence and outcome of prior autoimmune diseases in patients with aplastic anemia reported to the registry of the European group for blood and marrow transplantation.

Acta Haematol 2010 6;124(1):19-22. Epub 2010 Jul 6.

Pediatric Hematology Oncology, Department of Pediatrics, University of Padua, Padua, Italy.

Background: Aplastic anemia (AA) is rarely described after a diagnosis of autoimmune disease (aID).

Aims: To assess the prevalence of prior aID in patients with AA recorded in the registry of the European Group for Blood and Marrow Transplantation (EBMT) and to evaluate treatment and outcome.

Methods: 1,251 AA patients from 18 EBMT centers were assessed.

Results: Fifty patients (4%) were eligible: 22 males and 28 females with a median age of 46 years at the diagnosis of aID and of 51 years at the diagnosis of AA. Information on the treatment of AA was available in 49 patients: 38 received only immunosuppressive therapy (IST), 8 patients underwent hematopoietic stem cell transplantation (HSCT) - 6 as first-line therapy and 2 after failure of IST - whilst 3 patients had a spontaneous recovery. After a median follow-up of 3.19 years, 32 patients were alive, including 7 of the 8 patients who underwent HSCT. Only 6 of 32 patients who were alive at the last follow-up were receiving IST for AA.

Conclusions: Most cases of AA following aID benefitted from IST or HSCT if a matched donor was available. Further prospective investigation is needed to assess the effects of IST on the outcome of underlying aID.
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http://dx.doi.org/10.1159/000313783DOI Listing
August 2010

Impact of the intensity of the pretransplantation conditioning regimen in patients with prior invasive aspergillosis undergoing allogeneic hematopoietic stem cell transplantation: A retrospective survey of the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

Blood 2006 Nov 23;108(9):2928-36. Epub 2006 May 23.

Hematology Department of Sant Pau Hospital, Autonomous University of Barcelona, Spain.

In this retrospective study, we analyzed the outcomes of 129 patients who underwent an allogeneic hematopoietic stem cell transplantation (allo-HSCT) and had a history of probable or proven invasive aspergillosis (IA), of whom 57 (44%) received a reduced-intensity conditioning (RIC). Overall, 27 patients with IA progressed after the allo-HSCT (cumulative incidence [CumInc] at 2 years, 22%). The variables that increased the 2-year CumInc of IA progression were (1) longer duration of neutropenia after transplantation; (2) advanced status of the underlying disease; and (3) less than 6 weeks from start of systemic anti-Aspergillus therapy and the allo-HSCT. In addition, (4) conventional myeloablative conditioning increased the risk of progression early after transplantation (before day 30) only, while 3 variables increased the risk beyond day 30 were (5) cytomegalovirus disease; (6) bone marrow or cord blood as source of stem cells; and (7) grades II to IV acute graft-versus-host disease (GVHD). A risk model for progression was generated, defined as low (0-1 risk factors, 6% incidence), intermediate (2-3 risk factors, 27% incidence), or high risk (> or = 3 risk factors, 72% incidence [P < .001]). These findings may help in the interpretation and design of future studies on secondary prophylaxis of IA after an allo-HSCT.
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http://dx.doi.org/10.1182/blood-2006-03-008706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895522PMC
November 2006