P Sedlacek

University Hospital Motol, Praha, Praha, Czech Republic

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Publications (43)145.21 Total impact

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    ABSTRACT: Exact data on prognosis of children receiving invasive mechanical ventilation (IMV) after allogeneic hematopoietic SCT (HSCT) is lacking. We therefore started a prospective registry in four European university HSCT centers (Leiden, Paris, Prague and Utrecht) and their pediatric intensive care units (PICUs). The registry started in January 2009. In January 2013, the four centers together had treated a total of 83 admissions with IMV. The case fatality rate in these patients was 52%. Mortality 6 months after PICU discharge was 45%. There were significant differences between centers in the proportion of children who received IMV after HSCT (6-23%, P<0.01), in severity of disease on admission to PICU (predicted mortality 14-37%, P<0.01), in applying noninvasive ventilation before IMV (3-75% of admissions, P<0.01) and in the use of renal replacement therapy (RRT) (8-58% of admissions, P<0.01). Severe impairment in oxygenation, use of RRT and CMV viremia were independent predictors of mortality. Our study shows that mortality in children receiving IMV after HSCT remains high, but has clearly improved compared with older studies. Patient selection and treatment in PICU differed significantly between centers, which underscores the need to standardize and optimize the PICU admission criteria, ventilatory strategies and therapies applied in PICU.Bone Marrow Transplantation advance online publication, 28 July 2014; doi:10.1038/bmt.2014.147.
    Bone marrow transplantation. 07/2014;
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    ABSTRACT: We present case of a girl deceased due to Candida albicans -breakthrough invasive infection during the echinocandin treat-ment after undergoing allogeneic haematopoietic stem cell transplant for relaps of acute myeloid leukaemia. Candida albicans generally susceptible to all antifungal drugs wasn't considered for potential resistance and conventional blood culture positivity was too late to reveal the resistance to echinocandins. Due to severe organ toxicities (liver, kidneys) she received echinocandin as an antifungal prophylaxis, no change was made for the treatment of Candida albicans infection. Later, the molecular analysis proved the mutation S645P known as being responsible for the echinocandin resistance. The post mortem analysis of fungal burden in autopsy samples showed very high levels of Candida DNA in gut, liver, spleen and kidneys. Keywords: invasive candida dinase - haematopoietic stem cell transplant - echinocandin resistance.
    Epidemiologie, mikrobiologie, imunologie: casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne 06/2014; 63(2):121-124. · 0.31 Impact Factor
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    ABSTRACT: Human CMV infection is a frequent complication after HSC in children with remarkable morbidity and mortality. Antiviral drugs are relatively efficient but have numerous side effects. They are used as prophylactic, pre-emptive or therapeutic medicines. It is still a matter of debate which option is the best strategy. No uniform procedure has emerged regarding these three options, and new immunologic tools have raised more questions for physicians. To assess the current practice in the management of CMV infection, we sent a questionnaire to the EBMT centers performing hematopoietic SCT (HSCT) in children. Fifty-six out of 196 responded to the questionnaire (28.5%). Quantitative PCR was the most common monitoring tool (44/56). Only 4/56 centers use the pp65 antigenemia alone. All centers used pre-emptive strategy (56/56). 21/56 centers also used prophylactic measures, 13/21 after analysis of donor/receptor serologic status. Ganciclovir was the most common first-line agent for CMV disease (55/56). The most common dose and duration for induction treatment were 5 mg/kg bid (47/55) for 14 days (20/55). There is no uniform procedure for researching resistance strain, antiviral second-line therapy or cell therapy. A harmonization process should enable sound prospective trials to improve prevention, control and cure of CMV disease in children and adolescents.Bone Marrow Transplantation advance online publication, 28 October 2013; doi:10.1038/bmt.2013.164.
    Bone marrow transplantation 10/2013; · 3.00 Impact Factor
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    ABSTRACT: Based on the results from the AML-BFM 98 trial, hematopoietic SCT (HSCT) is recommended for children with AML in second CR only. Here, we retrospectively analyze interphase data of children who underwent HSCT after myeloablative conditioning with BU, CY, and melphalan (BuCyMel) for AML in second remission (CR2) between 1998 and 2009. Out of 152 children, transplant data were available on 109 individuals. Sixty out of 109 children (55%) received BuCyMel. Median age at HSCT was 12.2 years (range 3.0; 18.3). GVHD prophylaxis mostly consisted of CsA and short term MTX with or without antithymocyte globulin. Matched-sibling donors were used for 6/60 analyzed recipients, the remainder either received grafts from matched unrelated (30/60) or mismatched donors. OS after 5 years was 62% (s.e. 6%), relapse incidence 35% (18/60 children) and treatment-related mortality accounted for 12% (7/60) of fatal events. In conclusion, even taking into account possible selection bias in this retrospective analysis, HSCT in CR2 using BuCyMel resulted in a respectable OS. Based on this data the prospective, controlled and centrally monitored AML SCT-BFM 2007 trial has started to recruit patients in January 2010 aiming to generate valid outcome data for further strategy decisions.Bone Marrow Transplantation advance online publication, 29 October 2012; doi:10.1038/bmt.2012.204.
    Bone Marrow Transplantation 05/2013; 48(5):651-6. · 3.54 Impact Factor
  • Acta Medicinae. 01/2013; 2:31-33.
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    Dataset: AID Blood
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    ABSTRACT: To describe incidence, risk factors and treatment of autoimmune diseases (AD) occurring after cord blood transplantation (CBT), we analysed CBT recipients reported to EUROCORD having developed at least one new AD and those having not. Fifty-two out of 726 reported patients developed at least one AD within 212 (27-4267) days following CBT. The cumulative incidence of AD after CBT was 5.0±1% at 1 year and 6.6±1% at 5 years. Patients developing AD were younger and had more non-malignant diseases (p<0.001). AD target haematopoietic [autoimmune haemolytic anaemia (n=20), EVANS syndrome (n=9), autoimmune thrombocytopenia (n=11), immune neutropenia (n=1)] and other tissues [thyroiditis (n=3), psoriasis (n=2), Graves' disease (n=1), membranous glomerulonephritis (n=2), rheumatoid arthritis (n=1), ulcerative colitis (n=1) systemic lupus erythematosus (n=1)]. Four patients developed two AD (3 ITP followed by AIHA and 1 EVANS syndrome with rheumatoid arthritis). By multivariate analysis, the main risk factor for developing an AD was non-malignant disease as indication for CBT (p= 0.0001). Haematological AD were most often treated with steroids, rituximab and cyclosporine. With a median follow-up of 26 months (2-91 months), 6/52 patients died as a consequence of AD. CBT may be followed by potentially life-threatening, mainly haematological AD.
    Blood 12/2012; · 9.78 Impact Factor
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    ABSTRACT: There is no literature regarding the outcomes of allogeneic hematopoietic cell transplantation (HCT) for patients with XIAP deficiency. In order to estimate the success of HCT, we conducted an international survey of transplant outcomes. Data was reported for 19 patients. Seven patients received busulfan-containing myeloablative conditioning (MAC) regimens. Eleven patients underwent reduced intensity conditioning (RIC) regimens predominantly consisting of alemtuzumab, fludarabine, and melphalan. One patient received an intermediate intensity regimen. Survival was poor in the MAC group, only 1 patient is surviving (14%). Most deaths were related to transplant related toxicities, including veno-occlusive disease and pulmonary hemorrhage. Of the 11 patients who received RIC, 6 patients are currently surviving at a median of 570 days following HCT (55%). Preparative regimen and HLH activity affected outcomes, and of RIC patients reported to be in remission from HLH, survival is 86% (p=0.03). We conclude that MAC regimens should not be used for patients with XIAP deficiency. It is possible that the loss of XIAP and its anti-apoptotic functions contributes to the high incidence of toxicities observed with MAC regimens. RIC regimens should be pursued with caution, and efforts should be made to ensure the remission of HLH prior to HCT if possible.
    Blood 11/2012; · 9.78 Impact Factor
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    ABSTRACT: Background: Mucormycosis is an invasive fungal disease severely complicating treatment of patients with hematologic diseases. Effective therapy is represented by the combination of surgery and amphotericin B administration and early initiation of the therapy is necessary for favorable outcome. The first clinical symptoms are usually non-specific and this can lead to late therapy onset. The objective of this retrospective work was to determine the frequency, risk factors and outcome of invasive mucormycosis in pediatric hematology patients. Material and methods: The study cohort comprised 399 patients diagnosed with hematologic diseases in the Department of Pediatric Hematology and Oncology (DPHO), University Hospital Motol, Prague between 2005 and 2010. Risk factors for the development of mucormycosis, clinical symptoms and radiology and laboratory results were retrospectively evaluated. So were the therapy used and outcomes. The findings were analyzed using Fisher's exact test. Results: During the selected period, mucormycosis was detected in 8 patients diagnosed with hematologic disease. The incidence of mucormycosis was 1.75 %. These conditions accounted for 20.6 % of all mycoses. In five patients, it was found as isolated infection; three cases were associated with other mycoses (one with candidiasis, two with aspergillosis). The most frequent underlying disease was acute leukemia; the most common risk factor was severe prolonged neutropenia (median duration 21.5 days). Three of eight patients survived mucormycosis, a mortality rate of 62.5 %. The effective therapy was amphotericin B administration in three patients (p = 0.02); in two of them, it was combined with radical surgery. Conclusion: In the cohort, the proportion of mucormycosis cases was surprisingly high when compared with other fungal diseases. Continuous surveillance of mucormycosis in the DPHO is needed. There was no significant influence of the combination of radical surgery and amphotericin B administration as compared to administration of amphotericin B alone. Nevertheless, according to the published data, we consider this approach as an optimal strategy for the management of mucormycosis at the present time.
    Klinicka mikrobiologie a infekcni lekarstvi 08/2012; 18(4):102-108.
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    ABSTRACT: Experience with allogeneic hematopoietic cell transplantation (HCT) of patients with XIAP deficiency is limited. We conducted an international survey to estimate outcomes. Nineteen patients underwent allogeneic HCT at a median age of 3 years (range 0.4-19). Twelve patients received reduced intensity conditioning (RIC) regimens and 7 received myeloablative conditioning (MAC) regimens. Patients received grafts from matched (n=11) or single allele mismatched (n=8) grafts. All but 2 grafts were from unrelated donors. Only 1 of the 7 patients who received MAC is surviving (14%), and 6 of the 12 patients who received RIC are surviving (50%), at a median of 414 days following HCT (range 139-1765). The most common causes of death included hepatic veno-occlusive disease, pneumonitis or ARDS, pulmonary hemorrhage, multi-organ failure, and sepsis. We conclude that the survival of patients with XIAP deficiency is poor compared to other forms of HLH and XLP. MAC regimens appear contraindicated.
    2012 Clinical Immunology Society Annual Meeting; 05/2012
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    ABSTRACT: A collection of 178 Aspergillus isolates, recovered from Czech patients, mostly from 2007-2011, was subjected to multilocus DNA sequence typing using the ITS region, β-tubulin, and calmodulin genes. An unusually wide spectrum of etiologic agents that included 36 species of Aspergillus is discussed in the context of recent taxonomic and clinical reports. Invasive aspergillosis (IA), onychomycosis, and otitis externa were the predominant clinical entities. Five cases due to species newly proven as etiologic agents of human mycoses, as well as cases with unique clinical manifestations caused by unusual agents are discussed in more detail. Three species (i.e., A. insulicola, A. westerdijkiae and A. tritici) were identified as the confirmed etiologic agents of non-dermatophytic onychomycosis. Emericella rugulosa was recovered from a premature newborn with a fatal necrotising disseminated infection and is reported for only the second time as the cause of IA. Furthermore, we document the first infection due to A. calidoustus in a patient with chronic granulomatous disease. The infection manifested as a latent brain aspergilloma with an unusual clinical-laboratory finding. In addition to the well-known agents of human mycosis, several rarely isolated or poorly documented species were identified. An undescribed cryptic species related to A. versicolor was found to be common among isolates linked to proven and probable onychomycosis. An isolate representing A. fresenii, or an unnamed sister species, were causal agents of otomycosis. Three well defined, and tentative new species belonging to section Cervini, Candidi and Aspergillus (Eurotium spp.), were associated with cases of probable onychomycosis.
    Medical mycology: official publication of the International Society for Human and Animal Mycology 03/2012; 50(6):601-10. · 2.13 Impact Factor
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    ABSTRACT: Hepatic veno-occlusive disease is a leading cause of morbidity and mortality after haemopoietic stem-cell transplantation (HSCT). We aimed to assess whether defibrotide can reduce the incidence of veno-occlusive disease in this setting. In our phase 3 open-label, randomised controlled trial, we enrolled patients at 28 European university hospitals or academic medical centres. Eligible patients were younger than 18 years, had undergone myeloablative conditioning before allogeneic or autologous HSCT, and had one or more risk factor for veno-occlusive disease based on modified Seattle criteria. We centrally assigned eligible participants on the basis of a computer-generated randomisation sequence (1:1), stratified by centre and presence of osteopetrosis, to receive intravenous defibrotide prophylaxis (treatment group) or not (control group). The primary endpoint was incidence of veno-occlusive disease by 30 days after HSCT, adjudicated by a masked, independent review committee, in eligible patients who consented to randomisation (intention-to-treat population), and was assessed with a competing risk approach. Patients in either group who developed veno-occlusive disease received defibrotide for treatment. We assessed adverse events to 180 days after HSCT in all patients who received allocated prophylaxis. This trial is registered with ClinicalTrials.gov, number NCT00272948. Between Jan 25, 2006, and Jan 29, 2009, we enrolled 356 eligible patients to the intention-to-treat population. 22 (12%) of 180 patients randomly allocated to the defibrotide group had veno-occlusive disease by 30 days after HSCT compared with 35 (20%) of 176 controls (risk difference -7·7%, 95% CI -15·3 to -0·1; Z test for competing risk analysis p=0·0488; log-rank test p=0·0507). 154 (87%) of 177 patients in the defibrotide group had adverse events by day 180 compared with 155 (88%) of 176 controls. Defibrotide prophylaxis seems to reduce incidence of veno-occlusive disease and is well tolerated. Thus, such prophylaxis could present a useful clinical option for this serious complication of HSCT. Gentium SpA, European Group for Blood and Marrow Transplantation.
    The Lancet 02/2012; 379(9823):1301-9. · 39.21 Impact Factor
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    ABSTRACT: We present case of female patient who developed mucormycosis of right forearm and elbow during the initial stage of the induction phase of ALL relapse treatment. Surgical removal of the affected tissues and auto-transplantation of skin, in combination with systemic therapy with amphotericin B lipid complex (ABLC) led to practically complete recovery. Only a small defect remained on the patient‘s elbow, which is being treated conservatively. Mucormycosis interrupted the induction therapy of the main malignancy and delayed the chemotherapy protocols. Nevertheless the therapy of leukaemia was successfully completed and the relapse prognosis was uninfluenced.
    Postgrad Med. 01/2012; 2012(14):54-6.
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    ABSTRACT: Diagnosis of non-Aspergillus mould infections remains challenging despite application of a wide spectrum of non-culture-based microbiological techniques. Invasive diagnostic procedures are often essential. Here we present the case of 4 years old girl diagnosed with Coprinellus domesticus (anamorph Hormographiella verticillata) pneumonia during induction chemotherapy for acute lymphoblastic leukaemia. She was effectively treated with amphotericin B lipid complex during ongoing intensive chemotherapy and subsequently underwent allogeneic hematopoietic stem cell transplantation from unrelated donor. Voriconazole was used as long term secondary prophylaxis.
    Postgrad Med. 01/2012; 2012(14):51-3.
  • P. Sedlacek, V. Chrenkova, P. Keslova
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    ABSTRACT: Invasive fungal infection (IFI) continues to be frequent cause of morbidity and mortality in neonates and in both immunocompromised and immunocompetent children. Although these infections have been well characterized in adults, incidence, diagnostic tools, analysis of risk factors and treatment outcomes have not been well described in children. Data regarding the efficacy, safety and proper dosing of widely used antifungals in children of different age categories still remain to be solved. In this paper we would like to summarize news published about this specific topic of pediatrics over year 2010 and excerpted in PubMed database.
    Pediatr. praxi. 01/2011; 12(2):98-101.
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    ABSTRACT: We report on the outcome of children with advanced primary myelodysplastic syndrome (MDS) transplanted from an HLA-matched sibling (MSD) or an unrelated donor (UD) following a preparative regimen with busulfan, cyclophosphamide and melphalan. Ninety-seven patients with refractory anemia with excess blasts (RAEB, n=53), RAEB in transformation (RAEB-T, n=29) and myelodysplasia-related acute myeloid leukemia (MDR-AML, n=15) enrolled in the European Working Group of MDS in Childhood (EWOG-MDS) 98 study and given hematopoietic stem cell transplantation (HSCT) were analyzed. Median age at HSCT was 11.1 years (range 1.4-19.0). Thirty-nine children were transplanted from an MSD, whereas 58 were given the allograft from a UD (n=57) or alternative family donor (n=1). Stem cell source was bone marrow (n=69) or peripheral blood (n=28). With a median follow-up of 3.9 years (range 0.1-10.9), the 5-year probability of overall survival is 63%, while the 5-year cumulative incidence of transplantation-related mortality (TRM) and relapse is 21% each. Age at HSCT greater than 12 years, interval between diagnosis and HSCT longer than 4 months, and occurrence of acute or extensive chronic graft-versus-host disease were associated with increased TRM. The risk of relapse increased with more advanced disease. This study indicates that HSCT following a myeloablative preparative regimen offers a high probability of survival for children with advanced MDS.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 01/2011; 25(3):455-62. · 10.16 Impact Factor
  • Bone Marrow Transplantation: 37th European Group for Bone and Marrow Transplantation., Paris, France.; 01/2011
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    ABSTRACT: Incidence zygomykóz narůstá. Invazivní zygomykózy jsou významnou příčinou morbidity a mortality pacientů s hematologickými onemocněními.1 U mnoha pacientů je současně nezbytné pokračovat v chemoterapii v co nejkratší době. Diseminované onemocnění především u kojenců probíhá fatálně. Stále častěji jsou v léčbě invazivních zygomykóz používány kombinace antimykotik. Často izolovaný a dobře popsaný druh zygomycet, který bývá u imunokompromitovaných pacientů původcem invazivní infekce, je Rhizopus microsporus. Uvádíme zde případ kojence léčeného pro akutní lymfoblastickou leukemii (ALL), u kterého jsme diagnostikovali invazivní diseminovanou infekci patogenem Rhizopus microsporus měsíc po zahájení intenzivní chemoterapie. Operace a přechodná léčba kombinací lipidového komplexu amfotericinu B (ABLC) s caspofunginem umožnily pokračovat v intenzivní chemoterapii. Posaconazol nebyl v první linii užit. Echinokandiny v kombinaci s polyeny či posaconazolem byly zkoumány pro potenciální synergický účinek proti zygomycetám. Námi testované tři kombinace antimykotik (amfotericin B a caspofungin, amfotericin B a posaconazol, caspofungin a posaconazol) neprokázaly u klinického izolátu žádnou synergii in vitro. Dlouhodobá účinná a dobře snášená léčba ABLC u našeho pacienta vedla ke kompletnímu vymizení infekce.
    Farmakoterapie. 01/2011; 7:233-380.
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    ABSTRACT: Depletion of cellular immunity as a consequence of conditioning before allogeneic hematopoietic SCT (HSCT) frequently results in CMV reactivation, which may in turn lead to life-threatening infections and require timely antiviral treatment. We have investigated the functional signatures of CMV-specific CD4+ and CD8+ T-cells in 191 samples from 118 individuals. We compared healthy donors with both patients with high and undetectable viral loads, and those who controlled and did not control their CMV reactivations. Polychromatic flow-cytometric measurements of CD154 (CD40L), intracellular cytokines (IFNγ, IL2) and a degranulation marker (CD107a) allowed us to assess the functional status of various T-cells simultaneously. We found that dual IFNγ/IL2-producing CD8+ T-cells were present in patients controlling their CMV reactivations but absent from non-controllers. CD8+ T-cells that produce only IFNγ were the most abundant subtype, but they most likely represent non-protective memory cells. Distinct functional signatures were examined by hierarchical clustering, and this revealed that, unlike polyfunctional CD8+ T-cells, CD8+ T-cells that produce IFNγ alone were not functioning in concert with other subsets. In conclusion, our study revealed functional signatures that may be useful for immune monitoring, and it could change the interpretation of previous studies that assessed only IFNγ.
    Bone marrow transplantation 11/2010; 46(8):1089-98. · 3.00 Impact Factor
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    ABSTRACT: Introduction Infection et maladie à CMV sont des complications graves et fréquentes en greffe de CSH. Morbidité et mortalité ont diminué grâce à des stratégies prophylactiques et préemptives basées sur différents tests diagnostiques et drogues antivirales, sans qu’aucune étude comparative ni aucun consensus n’existe. Nous avons mené une enquête européenne afin de faire un état des lieux de la prise en charge pédiatrique du CMV. Matériel et Méthode Envoi à tous les centres EBMT d’un questionnaire de 40 items portant sur les modalités diagnostiques, le schéma de suivi, le type de stratégies (prophylactique, préemptive, curative), les modalités de traitement, la définition de l’échec thérapeutique, la recherche de résistances aux antiviraux, et le recours aux thérapies cellulaires et bithérapies. Résultats Au 17/02, 61 centres de 21 pays ont répondu. L’ensemble des résultats seront présentés et discutés à l’occasion du congrès de la SFP. Quelque soit l’aspect considéré - monitoring, stratégie, drogue utilisée en première et seconde ligne, durée du traitement etc., chaque centre a « sa » propre procédure. Conclusion Des études comparatives dans des centres aux procédures différentes doivent être réalisées afin d’arriver à l’établissement d’une procédure consensuelle.
    Archives De Pediatrie - ARCHIVES PEDIATRIE. 01/2010; 17(6):6-6.

Publication Stats

304 Citations
145.21 Total Impact Points

Institutions

  • 2001–2014
    • University Hospital Motol
      Praha, Praha, Czech Republic
  • 2008
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands
  • 2005–2007
    • University of Freiburg
      • Department of Pediatrics
      Freiburg, Baden-Württemberg, Germany
  • 2001–2007
    • Charles University in Prague
      Praha, Praha, Czech Republic
  • 2004
    • National Museum, Prague, Czech Republic
      Praha, Praha, Czech Republic