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1.
Pediatr Blood Cancer ; 69(10): e29750, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35484955

RESUMO

BACKGROUND: Sweden adopted a different strategy than many other countries to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and kept most schools open. Initial reports from China suggested that coronavirus disease 2019 (COVID-19) was milder in children compared to adults, but there was a lack of data from immunocompromised children. Therefore, we investigated the rate of verified SARS-CoV-2 infections in our Swedish pediatric oncology patients. PROCEDURE: This was a multicenter retrospective study. A questionnaire including patient data as well as SARS-CoV-2 data was sent to the six Swedish childhood cancer centers in May 2021. RESULTS: During the first pandemic year, 49 patients were identified as SARS-CoV-2 positive, and 22 (45%) children were hospitalized with COVID-19. Two children needed intensive care, but no COVID-19-related deaths were reported. Most patients (n = 36, 73%) were on active chemotherapy treatment and 23 children (49%) attended school or daycare at least part-time. Half of the SARS-CoV-2-positive patients experienced a delay in cancer treatment. CONCLUSIONS: Despite the rapid spread of SARS-CoV-2 in Sweden, without a strict lockdown of the society, the number of nationally reported pediatric oncology patients with polymerase chain reaction (PCR)-verified infection was low, and the majority of children had mild disease. Our data show that treatment interruptions occurred frequently and this should clearly be avoided for the coming years.


Assuntos
COVID-19 , Neoplasias , Adulto , COVID-19/epidemiologia , Criança , Controle de Doenças Transmissíveis , Humanos , Neoplasias/epidemiologia , Neoplasias/terapia , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Suécia/epidemiologia
2.
Pediatr Hematol Oncol ; 38(3): 216-226, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33150834

RESUMO

Clofarabine has been shown to effectively induce remission in children with refractory leukemia. We conducted a prospective trial (clinicval.trials.gov NCT01025778) to explore the use of clofarabine-based chemotherapy as a bridge-to-transplant approach. Children with refractory acute leukemia were enrolled to receive two induction courses of clofarabine, etoposide, and cyclophosphamide (CloEC). Responding patients were scheduled for T-cell depleted haploidentical hematopoietic stem cell transplantation (HSCT). The primary objective was to improve survival by achieving sufficient disease control to enable stem cell transplantation. Secondary objectives were to evaluate safety and toxicity. Seven children with active disease entered the study. Two children responded to induction courses and underwent transplantation. Five children did not respond to induction: one died in progression after the first course; two received off-protocol chemotherapy and were transplanted; and two succumbed to progressive leukemia. All transplanted children engrafted and no acute skin graft-versus-host disease > grade I was observed. One child is alive and well 7.5 years after the first CloEC course. One child developed fulminant adenovirus hepatitis and died in continuous complete remission 7 months after start of induction. Two children relapsed and died 6.5 and 7.5 months after enrollment. Infection was the most common toxicity. CloEC can induce responses in some patients with refractory acute leukemia but is highly immunosuppressive, resulting in substantial risk of life-threatening infections. In our study, haploidentical HSCT was feasible with sustained engraftment. No clinically significant organ toxicity was observed. Also, repeating CloEC probably does not increase the chance of achieving remission.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Clofarabina/uso terapêutico , Ciclofosfamida/uso terapêutico , Etoposídeo/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
3.
Blood ; 128(3): 440-8, 2016 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-27216217

RESUMO

Chronic granulomatous disease (CGD) can be cured by allogeneic hemopoietic stem cell transplantation (HSCT). Complications include graft failure, graft-versus-host disease (GVHD), infection, and transplant-related mortality; therefore, reduced-intensity conditioning regimens are being used to improve outcomes. In this retrospective study, the aim was to determine the outcome of treosulfan-based conditioning in HSCT for pediatric patients with CGD. The following data were collected: risk features pre-HSCT, additional conditioning agents, donor type and stem cell source, toxicity, engraftment, GVHD, chimerism, viral reactivation, post-HSCT complications, length of follow-up, and outcome. Seventy patients (median age, 107 months; interquartile range [IQR], 46-232 months) from 16 centers worldwide were transplanted between 2006 and 2015. Ninety-one percent had high-risk features. Fifty-seven HLA-matched donors, 12 HLA-mismatched donors, and 1 CD3(+)TCR αß/CD19 depleted parental haploidentical transplants were performed. No major toxicity was reported. Median times to neutrophil and platelet engraftment were 17 (IQR, 15-35) and 16 (IQR, 13-50) days. At a median follow-up of 34 months (IQR, 13-102 months), the overall survival was 91.4%, and event-free survival was 81.4%. The cumulative incidence of acute grade III-IV GVHD was 12%. Nine patients developed chronic GVHD. When split cell chimerism was available, 95% or more myeloid donor chimerism was documented in 80% of surviving patients. Secondary graft failure occurred in 12% of patients. Treosulfan-containing conditioning regimens can be used safely in HSCT for children with CGD and high-risk clinical features, achieving excellent survival with high myeloid chimerism. Further studies are needed to compare with other regimens and evaluate the long-term outcome, particularly on fertility.


Assuntos
Bussulfano/análogos & derivados , Doença Granulomatosa Crônica , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante/métodos , Doença Aguda , Adolescente , Adulto , Aloenxertos , Plaquetas/metabolismo , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Sobrevivência de Enxerto/efeitos dos fármacos , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/mortalidade , Doença Granulomatosa Crônica/sangue , Doença Granulomatosa Crônica/mortalidade , Doença Granulomatosa Crônica/terapia , Humanos , Lactente , Masculino , Neutrófilos/metabolismo , Taxa de Sobrevida
5.
Cytometry B Clin Cytom ; 92(5): 380-388, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-26647177

RESUMO

BACKGROUND: Cytomegalovirus (CMV) specific T-cells are known to provide long-term control of CMV reactivation, which is a frequent complication of hematopoietic stem cell transplantation. We have studied 58 pediatric patients after hematopoietic stem cell transplantation who suffered from CMV reactivation to reveal which functional T cell subset is best correlating with successful reactivation resolution and which protects from reactivation episode. METHODS: Detection of 30 combinatorial subsets of four types of response to ex vivo CMV stimulation (IFNγ secretion, IL-2 secretion, CD40L upregulation and degranulation) that were detectable on either CD8+ or CD4+ T cells through flow cytometry intracellular cytokine staining was used. RESULTS: We found that the presence of CD8+ dual positive (IFNγ+ and IL-2+) cells is the most accurate functional parameter that can predict fast resolution of CMV reactivation. Next, we show that the presence of CD8+ dual positive (IFNγ+ and IL-2+) and CD8+ IFNγ+ cells provides a protective effect (a hazard risk of 0.28 (confidence interval 0.18 - 0.43) and 0.45 (CI 0.27 - 0.75), respectively) and the presence of corticotherapy increases the risk of reactivation (HR 2.47 (CI 1.82-3.36)). Thus, a patient without corticotherapy and with both of the critical T cell subsets present has a cumulative 19.6 times lower risk of developing CMV reactivation than a patient on corticotherapy and without CD8+ dual positive (IFNγ+ and IL-2+) or CD8+ IFNγ+ cells. CONCLUSIONS: We have established parameters of CMV specific functional response ex vivo that can be used in assisting clinical management of patients with CMV reactivation. © 2015 International Clinical Cytometry Society.


Assuntos
Infecções por Citomegalovirus/virologia , Citomegalovirus/metabolismo , Transplante de Células-Tronco Hematopoéticas , Subpopulações de Linfócitos T/imunologia , Viremia/metabolismo , Adolescente , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Criança , Pré-Escolar , Feminino , Citometria de Fluxo/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Masculino , Adulto Jovem
6.
Mol Immunol ; 65(1): 139-47, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25656804

RESUMO

PURPOSE: PFAPA syndrome is a benign, recurrent inflammatory disease of childhood. Tonsillectomy is one of the therapeutic options with a yet unexplained biological mechanism. We tested whether specific lymphocyte subsets recruited from blood to human tonsils participate in PFAPA pathogenesis. METHODS: Paired tonsils/peripheral blood (PB) samples were investigated (a) from children with PFAPA that successfully resolved after tonsillectomy (n=10) (b) from children with obstructive sleep apnoea syndrome as controls (n=10). The lymphocyte profiles were analysed using 8-colour flow cytometry, immunoglobulin (IGH) and T-cell receptor (TCR) gene rearrangements via PCR and next generation sequencing; a TREC/KREC analysis was performed using qPCR. RESULTS: The PFAPA tonsils in the asymptomatic phase had a lower percentage of B-lymphocytes than controls; T-lymphocyte counts were significantly higher in PB. The percentages of cytotoxic CD8pos T-lymphocytes were approximately 2-fold higher in PFAPA tonsils; the transitional B cells and naïve stages of both the CD4pos and CD8pos T-lymphocytes with a low expression of PD-1 molecule and high numbers of TREC were also increased. With the exception of elevated plasmablasts, no other differences were significant in PB. The expression levels of CXCL10, CXCL9 and CCL19 genes were significantly higher in PFAPA tonsils. The IGH/TCR pattern showed no clonal/oligoclonal expansion. DNA from the Epstein-Barr virus, Human Herpervirus-6 or adenovirus was detected in 7 of 10 PFAPA tonsils but also in 7 of 9 controls. CONCLUSIONS: Our findings suggest that the uninhibited, polyclonal response of newly derived lymphocytes participate in the pathogenesis of PFAPA. Because most of the observed changes were restricted to tonsils and were not present in PB, they partly explain the therapeutic success of tonsillectomy in PFAPA syndrome.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Febre de Causa Desconhecida/imunologia , Tonsila Palatina/imunologia , Receptor de Morte Celular Programada 1/biossíntese , Subpopulações de Linfócitos T/imunologia , Adenoviridae/genética , Adenoviridae/isolamento & purificação , Linfócitos B/imunologia , Quimiocina CCL19/biossíntese , Quimiocina CXCL10/biossíntese , Quimiocina CXCL9/biossíntese , Criança , Pré-Escolar , Feminino , Febre de Causa Desconhecida/complicações , Febre de Causa Desconhecida/cirurgia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/isolamento & purificação , Humanos , Lactente , Linfadenite/complicações , Linfadenite/imunologia , Linfadenite/cirurgia , Contagem de Linfócitos , Masculino , Tonsila Palatina/citologia , Tonsila Palatina/cirurgia , Faringite/complicações , Faringite/imunologia , Faringite/cirurgia , Receptores de Antígenos de Linfócitos T/genética , Apneia Obstrutiva do Sono/imunologia , Apneia Obstrutiva do Sono/cirurgia , Estomatite Aftosa/complicações , Estomatite Aftosa/imunologia , Estomatite Aftosa/cirurgia , Tonsilectomia
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