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1.
Biomedicines ; 10(11)2022 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-36428483

RESUMO

The optimal bridging therapy before CAR-T cell infusion in pediatric relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL) still remains an open question. The administration of blinatumomab prior to CAR-T therapy is controversial since a potential loss of CD19+ target cells may negatively impact the activation, persistence, and, as a consequence, the efficacy of subsequently used CAR-T cells. Here, we report a single-center experience in seven children with chemorefractory BCP-ALL treated with blinatumomab before CAR-T cell therapy either to reduce disease burden before apheresis (six patients) or as a bridging therapy (two patients). All patients responded to blinatumomab except one. At the time of CAR-T cell infusion, all patients were in cytological complete remission (CR). Four patients had low positive PCR-MRD, and the remaining three were MRD-negative. All patients remained in CR at day +28 after CAR-T infusion, and six out of seven patients were MRD-negative. With a median follow-up of 497 days, four patients remain in CR and MRD-negative. Three children relapsed with CD19 negative disease: two of them died, and one, who previously did not respond to blinatumomab, was successfully rescued by stem cell transplant. To conclude, blinatumomab can effectively lower disease burden with fewer side effects than standard chemotherapeutics. Therefore, it may be a valid option for patients with high-disease burden prior to CAR-T cell therapy without clear evidence of compromising efficacy; however, further investigations are necessary.

2.
J Clin Med ; 11(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36079123

RESUMO

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for an increasing number of nonmalignant indications. Its use is restricted by severe transplant-related complications, including CMV infection; despite various prophylactic and therapeutic strategies, CMV reactivation has remarkable morbidity and mortality. The analysis included 94 children with nonmalignant disorder who underwent allogeneic HSCT in the Department of Pediatric Hematology, Oncology, and Bone Marrow Transplantation in Wroclaw during years 2016-2020. Twenty-seven (29%) children presented with CMV infection, including ten (10/27; 37%) with high level CMV viremia (10,000 copies/mL). Six patients experienced subsequent CMV reactivation. The first-line ganciclovir-based (GCV) treatment was insufficient in 40% (11/27) of children. Overall survival (OS) was significantly lower in children with high CMV viremia compared to those with low levels/no CMV [1yrOS High CMV = 0.80 (95% CI 0.41-0.95) vs. 1yrOS others = 0.96 (95% CI 0.89-0.99)]. Similarly, patients with resistant and recurrent infections had greater risk of death. CMV reactivation at any level relevantly prolonged the hospital stay. CMV reactivation with high viremia load and resistant/recurrent CMV infections lead to a significant decrease in OS in children with nonmalignant disorders treated with HSCT. Our data proves there is an urgent need to introduce an effective anti-CMV prophylaxis in this cohort of patients.

3.
Front Pediatr ; 10: 956108, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36071886

RESUMO

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a treatment method for a wide range of malignant and non-malignant diseases. Infants constitute a distinct patient group, especially due to their organ immaturity and differences in drug metabolism. The present paper aims to analyse the short- and long-term outcomes after allo-HSCT in infants. Material and methods: In the study period, 67 patients under 12 months of age underwent allo-HSCT. This study is a retrospective analysis of patient medical records, in the form of paper and electronic documentation. Results: The probability of 5-year OS was 69% and 72% in patients with malignant and non-malignant diseases, respectively. The allo-HSCT from a matched donor was associated with improved OS in comparison to haploidentical donor (0.8 vs. 0.58%, p = 0.0425). The overall incidence of acute graft-vs.-host disease (aGVHD) was 59.3%, and grade III-IV aGVHD was diagnosed in 23% of patients. The 100-day non-relapse mortality (NRM) in the study cohort was 17.9%, while the 5-year NRM was 26.9%. Among the causes of NRM, infections occurred in 83.3% of patients, and aGVHD in 16.3% of individuals. Twenty-two children (32.8%) required hospitalization in the pediatric intensive care unit (PICU). The median length of PICU hospitalization was 6 days (range 1 to 12 days). Late sequelae diagnosed during post-transplant surveillance included ocular disorders in 26.8% of patients, cardiac complications in 4.4%, as well as endocrinopathy with short stature (<3rd percentile) in 37.2% and overt hypothyroidism in 35.4%. In the long-term perspective, 83.3% of survivors were able to attend a regular school. Conclusions: Improvements in unrelated donor availability, and better supportive care resulted in better outcomes. Management of infant allo-HSCT recipients requires the formation of multi-disciplinary specialist teams. In addition, the role of parental empowerment must be acknowledged; for example, in speech therapy and rehabilitation.

4.
Front Pediatr ; 10: 861692, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402365

RESUMO

We report a child with Fanconi anemia who, after hematopoietic stem cell transplantation (HSCT) complicated by acute graft-versus-host disease (GVHD), underwent orthotopic liver transplantation (OLT). Approximately 1 month after OLT, the presence of third-party genetic material from the liver donor was noted and in the next few weeks, the chimerism assessment revealed 100% liver donor leukocytes in the peripheral blood. The rapidly progressing GVHD with gut involvement resulted in patient's death 6 months after OLT. The liver can act as a clinically significant source of hematopoietic stem cells, and the liver donor's young age must be emphasized as potentially predisposing to this phenomenon. Transfer of OLT hematopoietic stem cells may not have clinical significance unless the patient is not immunocompetent or develops liver-transplantation associated GVHD, that can result in lymphocyte mediated elimination of original hematopoiesis. Patients with preexisting immunity disorder (such as primary or secondary immunodeficiency) might require intensified immunosuppressive therapy in peritransplant period as a prevention of liver-transplantation associated GVHD. Close monitoring of hematopoietic chimerism after OLT is warranted in patients at risk, because cytopenia or OLT hematopoiesis can reflect subclinical GVHD and further studies are necessary to elucidate this phenomenon.

5.
Sci Total Environ ; 811: 152358, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-34921884

RESUMO

Bird collisions with windows are among the highest sources of human caused mortality to this group of animals. However, environmental correlates of spatial patterns in collision risk are poorly understood, thus making mitigation measures difficult to implement. We took advantage of Covid-19 lockdown in the spring of 2020, when people were obligated to stay mainly at home, and performed a memory-recall questionnaire survey concerning bird-window collisions in Poland. We received information on bird-window collisions with 1800 buildings across the whole country accompanied by characteristics of each building, its vicinity and resident's behavior (time spent home, window cleaning). We supplemented these data with landscape description and performed statistical models to estimate importance of 13 explanatory variables as predictors of number of bird-window collisions. Reported number of collisions increased with the share of forests and arable land within 2 km of the building, and with proximity to rivers. Number of collisions also increased when single trees were close to buildings. More collisions were reported for houses than for flats and for new buildings than for old ones. Reported number of collisions increased with window cleaning which might suggest that cleaning reduces glass visibility for birds. As bird-window collision risk is highly variable among buildings but can be reduced with several measures improving glass visibility for birds, we recommend to use predictive models to identify collision hotspots for applying these measures. New houses located near rivers, in forests or agricultural landscapes have highest collision risk, and trees near buildings, often planted to benefit birds, can additionally elevate collision rate, thus potentially creating ecological traps. In such collision hotspots, reduction of window cleaning frequency can be considered as a mitigation measure unless the visual markers improving glass visibility for birds are installed on the panels.


Assuntos
COVID-19 , Ciência do Cidadão , Animais , Aves , Controle de Doenças Transmissíveis , Humanos , Polônia , SARS-CoV-2
6.
Ann Hematol ; 101(1): 191-201, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34674000

RESUMO

The aim of this multi-center study was to evaluate the incidence, clinical course, and risk factors for bacterial multidrug-resistant (MDR) gastrointestinal tract infections (GTI) among children undergoing allogeneic and autologous hematopoietic cell transplantation. A total number of 175 pediatric patients (aged 1-18 years), transplanted between January 2018 and December 2019, who were tested for bacterial colonization/infection were enrolled into this multi-center analysis. Episodes of MDR GTI occurred in 77/175 (44%) patients. In multivariate analysis for higher GTI incidence, the following factors were significant: matched-unrelated donor (MUD) transplantation, HLA mismatch, presence of graft-versus-host disease (GVHD), and gut GVHD. The most common GTI were Clostridium difficile (CDI), multidrug-resistant Enterobacteriaceae (Klebsiella pneumoniae, Escherichia coli extended-spectrum ß-lactamase), and Enterococcus HLAR (high-level aminoglycoside-resistant). No MDR GTI-attributed deaths were reported. MDR GTI is a frequent complication after HCT among children, causes prolonged hospitalization, but rarely contributes to death. We identified risk factors of MDR GTI development in children, with focus on GVHD and unrelated donor and HLA mismatch. We conclude that the presence of Clostridiales plays an important anti-inflammatory homeostatic role and decreases incidence of GVHD or alleviate its course.


Assuntos
Infecções Bacterianas/etiologia , Gastroenteropatias/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Criança , Pré-Escolar , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/etiologia , Farmacorresistência Bacteriana Múltipla , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Incidência , Lactente , Masculino , Fatores de Risco , Transplante Autólogo/efeitos adversos , Transplante Homólogo/efeitos adversos
7.
J Clin Med ; 10(19)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34640434

RESUMO

Severe aplastic anemia (SAA) is a bone marrow failure syndrome that can be treated with hematopoietic cell transplantation (HCT) or immunosuppressive (IS) therapy. A retrospective cohort of 56 children with SAA undergoing transplantation with fludarabine-cyclophosphamide-ATG-based conditioning (FluCyATG) was analyzed. The endpoints were overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of graft versus host disease (GVHD) and CI of viral replication. Engraftment was achieved in 53/56 patients, and four patients died (two due to fungal infection, and two of neuroinfection). The median time to neutrophil engraftment was 14 days and to platelet engraftment was 16 days, and median donor chimerism was above 98%. The overall incidence of acute GVHD was 41.5%, and that of grade III-IV acute GVHD was 14.3%. Chronic GVHD was diagnosed in 14.2% of children. The probability of 2-year GVHD-free survival was 76.1%. In the univariate analysis, a higher dose of cyclophosphamide and previous IS therapy were significant risk factors for worse overall survival. Episodes of viral replication occurred in 33/56 (58.9%) patients, but did not influence OS. The main advantages of FluCyATG include early engraftment with a very high level of donor chimerism, high overall survival and a low risk of viral replication after HCT.

8.
Ann Hematol ; 100(5): 1283-1293, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33661334

RESUMO

BK virus is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic cell transplantation (HCT). Viruses can be found in urine and serum samples of immunocompromised patients. Malignant diseases, age, cell source, day of granulocyte reconstitution, conditioning regimen, or use of total body irradiation may play an important role in BKV epidemiology, development of hemorrhagic cystitis course, and outcome. The aim of this study was to evaluate the incidence, clinical course, and risk factors for BKV-HC in children undergoing HCT. A total number of 133 patients who were prospectively tested for BKV colonization/infection were enrolled into this multicenter analysis. Episodes of BKV-HC occurred in 36/133 (27%) enrolled subjects. In a univariate analysis for BKV-HC incidence, the following factors were significant: age >5 years, peripheral blood transplantation, matched unrelated donor (MUD) transplantation, busulfan-cyclophosphamide-melphalan conditioning regimen, and acute myeloblastic leukemia (AML) diagnosis. Presence of acute graft-versus-host disease (aGVHD) in liver and gut GVHD was a significant risk factor of BKV-HC. No BKV-attributed deaths were reported. In multivariate analysis, the incidence of HC was significantly higher in patients with AML, age >5 years, MUD transplants, and children with GVHD. HC is a frequent complication after HCT among children causes prolonged hospitalization but rarely contributes to death. We identified risk factors of BKV-HC development in children, with focus on aGVHD: we concluded that excessive immune reaction connected with GVHD and immunosuppression drugs might play a pivotal role in the development of BKV-HC.


Assuntos
Vírus BK/isolamento & purificação , Cistite/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Polyomavirus/etiologia , Infecções Tumorais por Vírus/etiologia , Adolescente , Criança , Pré-Escolar , Cistite/terapia , Feminino , Humanos , Incidência , Lactente , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Masculino , Infecções por Polyomavirus/terapia , Estudos Prospectivos , Fatores de Risco , Transplante Homólogo/efeitos adversos , Infecções Tumorais por Vírus/terapia
10.
Pediatr Transplant ; 25(5): e13875, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32949079

RESUMO

Respiratory viral infections are known causes of mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Here, we report a unique case of a child with viral pneumonia caused by coinfection with human metapneumovirus (MPV), respiratory syncytial virus (RSV), and SARS-CoV-2 after HSCT. A 9-year-old girl with acute lymphoblastic leukemia underwent allogeneic HSCT from a matched, unrelated donor. During the post-transplant period, in profound leukopenia (below 10 leukocytes/µL), she was diagnosed with SARS-CoV-2, MPV, and RSV pneumonia and was treated with ribavirin and chloroquine. Before leukocyte recovery, the girl became asymptomatic, and SARS-CoV-2 and RSV clearance was achieved. The shedding of SARS-CoV-2 stopped before immune system recovery, and one may hypothesize that the lack of an inflammatory response might have been a contributing factor to the mild clinical course. Post-transplant care in HSCT recipients with COVID-19 infection is feasible in regular transplant units, provided the patient does not present with respiratory failure. Early and repeated testing for SARS-CoV-2 in post-transplant patients with concomitant infection mitigation strategies should be considered in children after HSCT who develop fever, respiratory symptoms, and perhaps gastrointestinal symptoms to control the spread of COVID-19 both in patients and in healthcare workers in hospital environments. Training of staff and the availability of personal protective equipment are crucial for containing SARS-CoV-2 infection.


Assuntos
COVID-19/imunologia , COVID-19/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , SARS-CoV-2 , Anemia Aplástica/patologia , Medula Óssea/patologia , COVID-19/complicações , Criança , Feminino , Humanos , Metapneumovirus , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Período Pós-Operatório , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/virologia , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/terapia , Vírus Sinciciais Respiratórios , Ribavirina/uso terapêutico , Transplante Homólogo , Tratamento Farmacológico da COVID-19
11.
Pediatr Transplant ; 24(5): e13765, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32558076

RESUMO

Allo-HSCT is associated with life-threatening complications. Therefore, a considerable number of patients require admission to a PICU. We evaluated the incidence and outcome of PICU admissions after allo-HSCT in children, along with the potential factors influencing PICU survival. A retrospective chart review of 668 children who underwent first allo-HSCT in the Department of Pediatric Hematology/Oncology and BMT in Wroclaw during years 2005-2017, particularly focusing on patients admitted to the PICU within 1-year post-HSCT. Fifty-eight (8.7%) patients required 64 admissions to the PICU. Twenty-four (41.5%) were discharged, and 34 (58.6%) patients died. Among the discharged patients, 6-month survival was 66.7%. Compared with survivors, death cases were more likely to have required MV (31/34; 91.2% vs. 16/24; 66.7% P = .049), received more aggressive cardiac support (17/34; 50% vs. 2/24; 8.3% P = .002), and had a lower ANC on the last day of their PICU stay (P = .004). Five patients were successfully treated with NIV and survived longer than 6 months post-discharge. The intensity of cardiac support and ANC on the last day of PICU treatment was independent factors influencing PICU survival. Children admitted to the PICU after allo-HSCT have a high mortality rate. Mainly those who needed a more aggressive approach and had a lower ANC on the last day of treatment had a greater risk of death. While requiring MV is associated with decreased PICU survival, early implementation of NIV might be considered.


Assuntos
Cuidados Críticos/estatística & dados numéricos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Adolescente , Criança , Pré-Escolar , Estado Terminal , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Modelos Logísticos , Masculino , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Transplante Homólogo , Adulto Jovem
12.
Bone Marrow Transplant ; 55(11): 2138-2146, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32398785

RESUMO

Hepatic veno-occlusive disease (VOD) is a potentially fatal complication following hematopoietic stem cell transplantation (HSCT). We evaluated in prospective analysis the usefulness of the pediatric EBMT criteria for VOD diagnosis and their presumable impact on cost effectiveness and patients' outcome. Study included all 282 HSCT procedures performed in Department of Pediatric Hematology/Oncology and BMT in Wroclaw between January 2016 and March 2019. Data were compared with previous VOD research conducted in our center before year 2016. Twenty-five (8.9%) patients (median age 3.5 years) were diagnosed with VOD. Duration of defibrotide (DF) administration varied from 4 to 34 days (median: 16.5), with 96% response rate. Overall survival was 88%. If applying Baltimore and modified Seattle criteria, VOD incidence was 2.13% and 5.7%, respectively. Median diagnosis delay based on modified Seattle criteria was 3 days. Before 2016, VOD incidence was 4.9%, with 74% DF response rate (p = 0.033) and 56.2% OS (p = 0.008). After implementing new criteria length of hospitalization for VOD patients decreased by median of 12 days (p = 0.009). Earlier VOD diagnosis, facilitated by EBMT criteria, resulting in implementing immediate treatment significantly improved patients' outcome. Furthermore, it allows shortening of DF administration and minimizes length of hospital stay.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Criança , Pré-Escolar , Humanos , Incidência , Polidesoxirribonucleotídeos , Estudos Prospectivos
13.
Adv Clin Exp Med ; 29(3): 339-344, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32207590

RESUMO

BACKGROUND: Hepatic veno-occlusive disease (VOD) is a life-threatening complication following hematopoietic stem cell transplantation (HSCT) and associated with a high mortality rate. Therefore, accurate and immediate diagnosis is crucial for implementing appropriate treatment. OBJECTIVES: In our single-center retrospective study, we assessed the accuracy of the Modified Seattle Criteria in children and adolescents undergoing HSCT, and compared them to the diagnostic criteria recently established by the European Society for Blood and Marrow Transplantation (EBMT). MATERIAL AND METHODS: Retrospective analysis of medical records of 951 HSCT procedures performed in 850 children and young adults in the years 2001-2015 in the Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation of Wroclaw Medical University Supraregional Center of Pediatric Oncology "Cape of Hope" in Wroclaw, Poland. RESULTS: Among the 850 children, 48 were diagnosed with VOD according to the Modified Seattle Criteria (5.05%). Thirteen patients (27%) developed VOD later than within 20 days after transplantation, as required in the diagnostic criteria. Five of the 6 patients who died from VOD were diagnosed with late-onset VOD. Using the categories of symptoms described in the Modified Seattle Criteria, hepatomegaly and weight gain were the most common symptoms in the analyzed cohort (81.25% and 68.75%). Fourteen patients (29%) never demonstrated elevated plasma bilirubin level (>2 mg/dL), as suggested in the Modified Seattle Criteria. Twenty-nine patients (64%) had increased platelet consumption requiring daily transfusions. Only 5 patients with decreased plasma antithrombin III (ATIII) activity level (<80%) on the day of HSCT developed VOD despite supplementation of ATIII. CONCLUSIONS: The Modified Seattle Criteria seemed to not meet the special needs of the pediatric population. The new diagnostic criteria proposed by the EBMT appear to be more adequately tailored to the pediatric population and may significantly change the conception of VOD in the future. The surprisingly low incidence of VOD in our cohort may suggest a beneficial role of monitoring and early supplementation of ATIII.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/mortalidade , Adolescente , Criança , Humanos , Polônia , Estudos Retrospectivos , Adulto Jovem
14.
Pediatr Allergy Immunol ; 31(5): 537-543, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32150770

RESUMO

PURPOSE: The aim of this nationwide study was to evaluate the characteristics of bacterial infections (BI), invasive fungal disease (IFD), and viral infections (VI) in pediatric patients with PID after allogeneic hematopoietic stem cell transplantation (allo-HSCT). PATIENTS AND METHODS: In total, 114 HSCT recipients were enrolled into the study. At least one infectious complication (IC) was diagnosed in 60 (52.6%) patients aged 0.1-17.7 years, that is, 59.5% with SCID and 49.4% with non-SCID. RESULTS: Among 60 HSCT recipients diagnosed with at least one IC, 188 episodes of infectious complications (EIC) were recorded, that is, 46.8% of BI, 41.5% of VI, and 11.7% of proven/probable IFD. According to PID and HSCT donor type, the incidence of EIC was comparable (P = .679). The localization of infections differed significantly due to PID type (P = .002). After each HSCT donor type, the most common site of infection was GI. Overall, BI caused by Gram-positive strains (59.1%) were prevalent, especially Staphylococcaceae. The multidrug-resistant (MDR) pathogens were diagnosed in 52.3%, especially ESBL + Enterobacteriaceae. The profile of VI was comparable for SCID and non-SCID patients (P = .839). The incidence of IFD was comparable for each PID and HSCT donor type. Survival after infection was 91.5% and was comparable for PID and HSCT donor type. CONCLUSIONS: The rate of patients diagnosed with IC among pediatric PID-HSCT recipients did not depend on PID type, but rather on HSCT donor type. The localization of IC depended on PID and HSCT donor type. Within bacterial infections, predominated Gram-positive strains and the MDR pathogens were responsible for more than half of EIC.


Assuntos
Infecções Bacterianas , Transplante de Células-Tronco Hematopoéticas , Doenças da Imunodeficiência Primária , Viroses , Criança , Humanos , Incidência , Estudos Retrospectivos
15.
Pediatr Transplant ; 23(8): e13592, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31587440

RESUMO

BACKGROUND: The objective of the study was to analyze the profile of infections in children with BMF following alloHCT. METHODS: Data of 169 consecutive children with inherited and acquired BMF treated with alloHCT between 2012 and 2017 in Polish pediatric transplant departments were analyzed in registry-based retrospective study, with respect to the type of infection, and clinical outcome. RESULTS: At least 1 infection was diagnosed in 107/169 patients (60.4%). In total, 182 infections were diagnosed. The most common were VI (96; 52.7%), followed by BI (71; 39.0%), and FI (15; 8.2%), P < .001. The most common etiological factors of VI were as follows: CMV (38.5%), EBV (22.9%), and BK virus (24%); while of BI were as follows: Staphylococcus spp. (17; 23.9%), Enterococcus faecium (10; 14.1%), and Klebsiella pneumoniae (9; 12.7%). No difference was found between the occurrence of infections with respect to donor type, graft source, and conditioning type. GvHD had no impact on the incidence of VI, BI, and FI. Fifteen FI were diagnosed in 12 patients, of which 14 FI were diagnosed in children transplanted for FA. Of total 107 children, 9 died (8.4%), of which 4 (3.7%) due to infections: bacterial sepsis (2) and invasive FI (2). CONCLUSION: Infections in children with BMF following alloHCT remain an important cause of morbidity. Children with FA had high incidence of FI. In our analysis, aGvHD had no impact on the occurrence on infections, although the study was not strong enough to prove such a difference.


Assuntos
Transtornos da Insuficiência da Medula Óssea/cirurgia , Transplante de Células-Tronco Hematopoéticas , Infecções/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Transplante Homólogo , Adulto Jovem
16.
Adv Clin Exp Med ; 28(9): 1223-1228, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31430069

RESUMO

BACKGROUND: Unmanipulated haploidentical stem cell transplantation (haploSCT) with post-transplant cyclophosphamide is an option for patients with advanced hematologic malignancies. It offers a platform both for non-major histocompatibility complex-restricted alloimmunity due to killer-like immunoglobulin receptor (KIR)-mediated mechanisms of natural killer lymphocyte regulation and for classical T-cell mediated antileukemic effects. OBJECTIVES: The devastating long-term sequelae after total body irradiation (TBI) in children are encouraging omission of irradiation techniques in pediatric stem cell transplantations (SCT). MATERIAL AND METHODS: Five children, 4 with acute leukemia and 1 with hemophagocytic lymphohistiocytosis, aged from 1 to 10 years, underwent haploSCT with post-transplantation cyclophosphamide. In all children, the conditioning regimen consisted of chemotherapy without TBI. The graft material was bone marrow (BM) in 4 cases and peripheral blood stem cells in 1 case. Three out of 5 leukemic patients showed better KIR haplotype associated with augmented alloreactivity. RESULTS: Engraftment with complete donor chimerism was achieved in 4 patients, and 1 recipient died before leukocyte recovery. Three patients developed skin acute graft-versus-host-disease (aGvHD), 1 gut aGvHD and 1 liver aGvHD. In 2 recipients, chronic graft-versus-host-disease (cGvHD) was observed (1 limited and 1 extensive). The 4 engrafted patients were alive and in complete remission 3, 9, 32, and 36 months after transplantation. A T-cell count of 200 cells/uL was reached 90 days after haploSCT in all patients. CONCLUSIONS: HaploSCT with TBI-free protocols can be a viable option for heavily pretreated patients with advanced malignancies.


Assuntos
Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Criança , Pré-Escolar , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Lactente , Condicionamento Pré-Transplante , Irradiação Corporal Total
17.
Adv Clin Exp Med ; 28(9): 1185-1192, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31430073

RESUMO

BACKGROUND: Acute graft-versus-host disease (aGvHD) is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Identifying its risk factors would enable the proper prophylaxis and management, which may significantly improve the general outcome of children treated with HSCT. OBJECTIVES: The aim of this single-center, retrospective cohort study was to assess the potential risk factors for grades II-IV of aGvHD in children after the 1st allo-HSCT from an unrelated donor (UD), performed as a result of an underlying malignant disease. MATERIAL AND METHODS: From among patients who received HSCT in our center in the years 2004-2015, 237 were included in the study cohort. All the patients received standard aGvHD prophylaxis consisting of cyclosporine (CsA) and a short course of methotrexate (MTX). Various clinical and epidemiological features, the transplant proceedings, graft composition, conditioning regimens, as well as the duration and coherence of aGvHD prophylaxis were analyzed as potential risk factors for aGvHD. RESULTS: The incidence of II-IV aGvHD in the study cohort was 58.6%. The median time of the diagnosis of aGvHD was 18 days post-HSCT. In the multivariate analysis, risk factors significantly associated with grades II-IV of aGvHD were: myeloablative conditioning regimen containing total body irradiation (TBI-MAC) (RR (relative risk): 1.69; p = 0.03), premature termination of CsA administration due to its toxicity (RR: 1.99; p = 0.0003) and HSCT performed before the year 2009 (RR: 1.97; p = 0.0001). Donor and recipient age, donor-recipient sex mismatch, stem cell source, risk of disease, and amount of infused CD34+ cells seem to be insignificant as risk factors for aGvHD. The overall survival (OS) of patients with aGvHD was noticeably worse that in those who were aGvHD-free: 60.8% vs 74.1% (p = 0.08). CONCLUSIONS: The conditioning regimen and the proper aGvHD prophylaxis, including continuous CsA administration, have a major impact on aGvHD occurrence. According to our results, the termination of CsA therapy should be carefully considered, and avoided if possible.


Assuntos
Ciclosporina/administração & dosagem , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Criança , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Doadores não Relacionados
18.
Transfus Apher Sci ; 57(3): 316-322, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29880247

RESUMO

The purpose of the survey was to evaluate the development and current use of hematopoietic stem cell transplantation (HSCT) in Poland between 1989-2016. The data for analysis (indication, number of performed HSCT, HSCT type, donor type, and stem cell source, year) have been collected annually using a standardized form. In Poland, between 1989-2016, the number of pediatric transplant beds grew from one to 40 and number and rate of transplants increased annually from 1/year (0.8/10 million) to 186/year (248/10 million). During the analyzed time period 2506 HSCTs were performed, including 1718 (68.6%) allogeneic transplants (allo-HSCT) with142 in 2016 and 788 (31.4%) autologous transplants (auto-HSCT) with 44 in 2016. Among 1718 allo-HSCT, 74% were performed for malignancy (ALL 47.2%, AML 26.2%, MDS 10.8%, CML 8.1%, NHL/HD 6.1%, others 2.5%), and 26% for non-malignant disorders (SAA 41%, congenital immunodeficiencies 35.4%, hereditary bone marrow failure 16%, metabolic disorders 7%). Among 788 auto-HSCTs, 30.8% were done for hematological malignancy (NHL 41.2%, AML 23.9%, HD 17.7%, ALL 15.6%, other 1.5%), while the remaining 69.2% for solid tumors (neuroblastoma 59.8%, Ewing's sarcoma 20.4%, other 19.8%). In Poland, between 1989-2016, the infrastructure indispensable to perform HSCT in every child with indication for this therapeutic procedure was created, and HSCT became an important part of pediatric treatment, especially in pediatric oncology, hematology, and in primary immunodeficiencies.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Criança , Feminino , Humanos , Masculino , Polônia
19.
Adv Clin Exp Med ; 26(4): 695-701, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28691431

RESUMO

BACKGROUND: Management of febrile neutropenia in pediatric patients is challenging. Chest X-ray and CT scan help to identify infective foci; however, exposure to radiation is a risk factor for development of secondary cancer. For this reason, attention is paid to reducing radiation exposure. OBJECTIVES: The aim of the study was to define the role of LDCT examination in the early detection of pulmonary lesions in children during oncology or autoimmune treatment complicated by neutropenia-related fever. Additionally, we focused on the possibility to optimize image quality in low-dose protocols. MATERIAL AND METHODS: The study included 138 pediatric patients (mean age 8.08 years) with fever of 38.2°C or higher with an absolute neutrophil count of 10 mm with or without surrounding GGO or cavitations was sensitive at 77% and specific at 65% for fungal infection insert after neutrophil count: < 500/pL who underwent chest X-ray and LDCT in the maximal interval of 24 h. CT findings were compared with initial and final diagnosis as well as with clinical information. RESULTS: LDCT detected pulmonary abnormalities in 116 patients (84.06%) showing ground-glass opacities (GGO) (n = 79), nodules (n = 60) and air-space consolidations (n = 58). Radiologists correctly diagnosed infective lesions in 94 out of 116 patients (81.03%). The presence of random or pleural-based nodules. Diagnosis of pyogenic infection based on the presence of air-space consolidation, pleural effusion, GGO or centrilobular nodules showed a sensitivity of 78% and specificity of 67%, whereas patchy or diffuse GGO, interstitial thickening and/or air-space consolidation showed a high sensitivity of 81% and specificity of 68% for Pneumocystis jirovecii pneumonia. CONCLUSIONS: LDCT is an excellent modality in the diagnostic algorithm in patients with febrile neutropenia. It allows early detection and detailed characterization of pulmonary abnormalities. Using contrast, unenhanced CT examinations can further reduce radiation dose and diminish the number of complications without a negative influence on the diagnostic process.


Assuntos
Neutropenia Febril/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Neoplasias/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Criança , Pré-Escolar , Neutropenia Febril/etiologia , Feminino , Humanos , Lactente , Masculino , Neoplasias/complicações , Neoplasias/terapia , Doses de Radiação , Radiografia Torácica
20.
Adv Exp Med Biol ; 755: 143-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22826061

RESUMO

Deterioration of pulmonary function can be the sole symptom of early stages of pulmonary complications following allogeneic hematopoietic cells transplantation (alloHCT). The aim of the study was to evaluate the prevalence and types of pulmonary function abnormalities in allogenic cells recipients. Twenty three (5 children and 18 adults) allogeneic hematopoietic cells recipients who underwent pulmonary function assessment before and 6-12 months after alloHCT were included in the study. Forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), total lung capacity (TLC), and lung diffusion capacity for carbon dioxide (D(L)CO) were determined. Values <80% of predicted were considered abnormal. We found significant reductions of FVC, D(L)CO, and TLC after alloHCT. The most important reduction was noted in D(L)CO (pre-alloHCT of 85%±15% vs. post- alloHCT of 60% ± 21%, p< 0.05). Six patients (26%) presented with lung function impairment before alloHCT: obstructive lung disease (4%), restrictive lung disease (13%), and decreased D(L)CO (17%). In 19 patients (83%) pulmonary function abnormalities were demonstrated after alloHCT. The most common disturbance was a D(L)CO decrease that occurred in 16 patients (70%). In conclusion, frequency of pulmonary function abnormalities in patients after alloHCT is high. A diffusion capacity decrease and restrictive pattern of ventilation insufficiency develop in the majority of patients after alloHCT. It would be reasonable to include pulmonary function testing to standard periodic examination in patients qualified for, and after, alloHCT procedure.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pulmão/fisiopatologia , Adolescente , Adulto , Criança , Feminino , Volume Expiratório Forçado , Doença Enxerto-Hospedeiro/fisiopatologia , Humanos , Masculino , Capacidade de Difusão Pulmonar , Transplante Homólogo , Capacidade Vital
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