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2.
Leukemia ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578451

RESUMO

AML SCT-BFM 2007 was the first hematopoietic stem cell transplantation (HCT) trial in Germany to comply with the European Clinical Trials Directive, and aimed to standardize pediatric HCT for acute myeloid leukemia (AML) across centers in Germany, Austria, and the Czech Republic. Children with high-risk features and a good early response achieving a complete first remission (CR-1) and those in CR-2 after a first relapse were stratified to receive HCT from a matched donor after myeloablative conditioning consisting of busulfan, cyclophosphamide, and melphalan. Four-year EFS and OS were 61 and 70%. Cumulative incidence of relapse (CIR) was 22%. TRM was 15% and correlated with age reaching 9% (SE 3%) in children younger than 12 years and 31% (SE 9%) in older children and adolescents. Children with poorly responding primary disease or relapse were allocated to receive early HCT after a cytoreductive regimen with fludarabine, amsacrine, and cytarabine, followed by reduced intensity conditioning and prophylactic donor lymphocyte infusions. Four-year EFS and OS were 49 and 53%. CIR was 38% and TRM 11%. For patients with primary poor response disease, early use of RIC HCT followed by prophylactic DLI can induce long-term remissions in more than 50% (EFS 46% (SE 9%)).

3.
Placenta ; 88: 20-27, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31586768

RESUMO

INTRODUCTION: Leukemia Inhibitory Factor (LIF) regulates behavior of trophoblast cells and their interaction with immune and endothelial cells. In vitro, trophoblast cell response to LIF may vary depending on the cell model. Reported differences in the miRNA profile of trophoblastic cells may be responsible for these observations. Therefore, miRNA expression was investigated in four trophoblastic cell lines under LIF stimulation followed by in silico analysis of altered miRNAs and their associated pathways. METHODS: Low density TaqMan miRNA assays were used to quantify levels of 762 mature miRNAs under LIF stimulation in three choriocarcinoma-derived (JEG-3, ACH-3P and AC1-M59) and a trophoblast immortalized (HTR-8/SVneo) cell lines. Expression of selected miRNAs was confirmed in primary trophoblast cells and cell lines by qPCR. Targets and associated pathways of the differentially expressed miRNAs were inferred from the miRTarBase followed by a KEGG Pathway Enrichment Analysis. HTR-8/SVneo and JEG-3 cells were transfected with miR-21-mimics and expression of miR-21 targets was assessed by qPCR. RESULTS: A similar number of miRNAs changed in each tested cell line upon LIF stimulation, however, low coincidence of individual miRNA species was observed and occurred more often among choriocarcinoma-derived cells (complete data set at http://www.ncbi.nlm.nih.gov/geo/ under GEO accession number GSE130489). Altered miRNAs were categorized into pathways involved in human diseases, cellular processes and signal transduction. Six cascades were identified as significantly enriched, including JAK/STAT and TGFB-SMAD. Upregulation of miR-21-3p was validated in all cell lines and primary cells and STAT3 was confirmed as its target. DISCUSSION: Dissimilar miRNA responses may be involved in differences of LIF effects on trophoblastic cell lines.

5.
Bone Marrow Transplant ; 54(11): 1847-1858, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31089287

RESUMO

Although allogeneic hematopoietic stem-cell transplantation (HSCT) provides high cure rates for children with high-risk acute lymphoblastic leukaemia (ALL), relapses remain the main cause of treatment failure. Whereas donor killer cell immunoglobulin-like receptor (KIR) genotype was shown to impact on relapse incidence in adult myeloid leukaemia similar studies in paediatric ALL are largely missing. Effect of donor KIR genotype on transplant outcome was evaluated in 317 children receiving a first myeloablative HSCT from an HLA-matched unrelated donor or sibling within the prospective ALL-SCT-BFM-2003 trial. Analysis of donor KIR gene polymorphism revealed that centromeric presence and telomeric absence of KIR B haplotypes was associated with reduced relapse risk. A centromeric/telomeric KIR score (ct-KIR score) integrating these observations correlated with relapse risk (hazard ratio (HR) 0.58; P = 0.002) while it had no impact on graft-versus-host disease or non-relapse mortality. In multivariable analyses ct-KIR score was associated with reduced relapse risk (HR 0.58; P = 0.003) and a trend towards improved event-free survival (HR 0.76; P = 0.059). This effect proved independent of MRD level prior to HSCT. Our data suggest that in children with ALL undergoing HSCT after myeloablative conditioning, donor selection based on KIR genotyping holds promise to improve clinical outcome by decreasing relapse risk and prolonged event-free survival.

6.
Am J Hematol ; 94(8): 880-890, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31095771

RESUMO

Severe infections (SI) significantly impact on non-relapse mortality after hematopoietic stem cell transplantation (HSCT). We assessed 432 children and adolescents with acute lymphoblastic leukemia (ALL) after total body irradiation based myeloablative HSCT within the multicenter ALL-BFM-SCT 2003 trial for SI grade 3 or higher according to common terminology criteria for adverse events. A total 172 patients experienced at least one SI. Transplantation from matched unrelated donors (MUD) was associated with any type of SI in the pre-engraftment period (hazard ratio [HR]: 2.57; P < .001), and with any SI between day +30 and + 100 (HR: 2.91; P = .011). Bacterial (HR: 2.24; P = .041) and fungal infections (HR: 4.06; P = .057) occurred more often in the pre-engraftment phase and viral infections more often before day +30 (HR: 2.66; P = .007) or between day +30 and + 100 (HR: 3.89; P = .002) after HSCT from MUD as compared to matched sibling donors. Chronic GvHD was an independent risk factor for any type of SI after day +100 (HR: 2.57; P < .002). We conclude that allogeneic HSCT from MUD in children and adolescents with pediatric ALL is associated with higher infection rates, which seems attributable to an intensified GvHD prophylaxis including serotherapy and methotrexate.

7.
Biol Blood Marrow Transplant ; 25(9): 1786-1791, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31082473

RESUMO

Gonadal impairment is an important late effect with a significant impact on quality of life of transplanted patients. The aim of this study was to compare gonadal function after busulfan (Bu) or treosulfan (Treo) conditioning regimens in pre- and postpubertal children. This retrospective, multicenter study included children transplanted in pediatric European Society for Blood and Marrow Transplantation (EBMT) centers between 1992 and 2012 who did not receive gonadotoxic chemoradiotherapy before the transplant. We evaluated 137 patients transplanted in 25 pediatric EBMT centers. Median age at transplant was 11.04 years (range, 5 to 18); 89 patients were boys and 48 girls. Eighty-nine patients were prepubertal at transplant and 48 postpubertal. One hundred eighteen children received Bu and 19 Treo. A higher proportion of girls treated with Treo in the prepubertal stage reached spontaneous puberty compared with those treated with Bu (P = .02). Spontaneous menarche was more frequent after Treo than after Bu (P < .001). Postpubertal boys and girls treated with Treo had significantly lower luteinizing hormone levels (P = .03 and P = .04, respectively) compared with the Bu group. Frequency of gonadal damage associated with Treo was significantly lower than that observed after Bu. These results need to be confirmed in a larger population.

8.
Front Immunol ; 10: 722, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31024554

RESUMO

Here we present a simple and sensitive flow cytometric-based assay to assess T cell proliferation. Given the critical role STAT5A phosphorylation in T cell proliferation, we decided to evaluate phosphorylation of STAT5A as an indicator of T cell proliferation. We determined pSTAT5A in T cell treated with either CD3/CD28 or PHA. After stimulation, T cells from adult healthy donors displayed a strong long-lasting phosphorylation of STAT5A, reaching a peak value after 24 h. The median fluorescence intensity (MFI) of pSTAT5A increased from 112 ± 17 to 512 ± 278 (CD3/CD28) (24 h) and to 413 ± 123 (PHA) (24 h), the IL-2 receptor-α (CD25) expression was greatly enhanced and after 72 h T cell proliferation amounted to 52.3 ± 10.3% (CD3/CD28) and to 48.4 ± 9.7% (PHA). Treatment with specific JAK3 and STAT5 inhibitors resulted in a complete blockage of phosphorylation of STAT5A, CD25 expression, and suppression of T cell proliferation. Compared with currently available methods, STAT5A phosphorylation is well-suited to predict T cell proliferation. Moreover, the method presented here is not very time consuming (several hours) and delivers functional information from which conclusions about T cell proliferation can be drawn.

9.
BMJ Case Rep ; 12(3)2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30936335

RESUMO

Therapies of complementary and alternative medicine (CAM) are used increasingly in paediatric oncology. We present and discuss the influence of supportive mistletoe therapy on factors, such as quality of life, physical ability and performance, and course of disease based on the case of a female patient diagnosed at age 18 with metastasised neuroblastoma, which responded insufficiently to chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/patologia , Neuroblastoma/patologia , Extratos Vegetais/administração & dosagem , Atividades Cotidianas , Adolescente , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/fisiopatologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/fisiopatologia , Escolaridade , Feminino , Humanos , Neuroblastoma/tratamento farmacológico , Neuroblastoma/fisiopatologia , Fitoterapia , Qualidade de Vida , Resultado do Tratamento
10.
Am J Transplant ; 19(6): 1798-1805, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30586230

RESUMO

We report data obtained from a retrospective multicenter pediatric survey on behalf of the European Society for Blood and Marrow Transplantation (EBMT). Information on solid organ transplantation (SOT) performed in pediatric recipients of either autologous or allogeneic hematopoietic stem cell transplantation (HSCT) between 1984 and 2016 was collected in 20 pediatric EBMT Centers (25.6%). Overall, we evaluated data on 44 SOTs following HSCT including 20 liver (LTx), 12 lung (LuTx), 6 heart (HTx), and 6 kidney (KTx) transplantations. The indication for SOT was organ failure related to intractable graft-vs-host disease in 16 children (36.3%), acute or chronic HSCT-related toxicity in 18 (40.9%), and organ dysfunction related to the underlying disease in 10 (22.8%). The median follow-up was 10.9 years (95% confidence interval: 1.7-29.5). The overall survival rate at 1 and 5 years after SOT was 85.7% and 80.4%, respectively: it was 74% and 63.2% after LTx, 83.2% after HTx, and 100% equally after LuTx and KTx. This multicenter survey confirms that SOT represents a promising option in children with severe organ failure occurring after HSCT. Additional studies are needed to further establish the effectiveness of SOT after HSCT and to better understand the mechanism underlying this encouraging success.

11.
Bone Marrow Transplant ; 54(6): 867-876, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30531916

RESUMO

HLA-haploidentical haematopoietic stem cell transplantation (haplo-HSCT) is increasingly offered to patients with high-risk acute leukaemia. Unfortunately, haplo-HSCT is followed by a delayed immunoreconstitution. The aim of this EBMT registry study was to explore the clinical impact of lymphocyte subset counts after haplo-HSCT. We considered 144 leukaemic patients transplanted in the period 2001-2012. Pre-transplantation clinical variables and differential immune-cell counts (CD3, CD4, CD8 T cells, NK and B cells) measured before day 100 were evaluated for their capacity to predict overall survival, relapse mortality or non-relapse mortality (NRM). Negative prognostic factors for overall survival were advanced disease state at transplantation, host age and CMV seropositivity. Higher CD3, CD4 and CD8 counts were associated with a better overall survival and a lower NRM. Strikingly, when tested in multivariable analysis, higher CD3 and CD8 counts were still significantly associated with a lower NRM. These results indicate that an accelerated T-cell reconstitution correlates with less transplantation mortality, likely due to the protective role of T cells against viral infections. This observation suggests that CD8+ T-cell counts should be investigated as surrogate biomarkers of outcome in prospective haplo-HSCT trials.

12.
Int J Radiat Oncol Biol Phys ; 104(1): 137-143, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30593907

RESUMO

PURPOSE: This retrospective analysis aimed to address the efficacy of total nodal irradiation (TNI)-based reconditioning regimens in pediatric patients with graft failure/rejection after allogeneic hematopoietic cell transplantation. METHODS AND MATERIALS: Thirty-three pediatric patients with malignant (n = 25) and nonmalignant diseases (n = 8) were treated with a TNI-based reconditioning regimen. All patients received a 7-Gy single dose combined with anti-T lymphocyte antibody OKT3 (n = 16), anti-thymocyte globulin (n = 24), fludarabine (n = 31), and/or thiotepa (n = 28), followed by an infusion of peripheral blood stem cells (n = 31) or bone marrow transplant (n = 2). Twenty-eight of 33 patients had haploidentical family donors. RESULTS: After a median of 11 days, engraftment was seen in 32 of 33 children. Two children died 34 days after retransplantation because of either disease relapse or treatment-related multiple organ failure. Severe acute toxicity was reported in only 1 child (systemic inflammatory response syndrome-like reaction; recovery after cortisone treatment). The average follow-up was 60.2 months (range, 1.1-162.5 months). Event-free and overall survival rates at 2/5 years follow-up were 62.0%/58.6% and 65.1%/61.7%, respectively. Despite sustained engraftment, 12 patients died from disease relapse (n = 3), Moschkowitz syndrome (n = 1), or multiple organ failure (n = 8). Follow-up data were available for 18 of 21 survivors, with a median follow-up of 92.8 months (range, 3.6-162.5 months). Hypothyroidism was present in 78.6% of patients, and sex/growth hormonal insufficiencies were reported for 37.5%. Mean forced expiratory volume in 1 second after TNI was 84%; mean vital capacity was 79%. Severe growth failure (<3rd percentile) occurred in 28.6% (height) and 35.7% (weight) of patients. No secondary malignancies were reported. CONCLUSIONS: In the high-risk group of patients with graft failure/rejection after allogeneic hematopoietic cell transplantation, the TNI-based reconditioning regimen seems to allow sustained engraftment combined with a favorable toxicity profile, leading to long-term event-free and overall survival. Late toxicity after a median follow-up of over 7.5 years includes growth failure, manageable hormonal deficiencies, and a low risk of decrease of lung function.


Assuntos
Rejeição de Enxerto , Transplante de Células-Tronco Hematopoéticas , Imunossupressão/métodos , Irradiação Linfática/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Aloenxertos , Soro Antilinfocitário/uso terapêutico , Transplante de Medula Óssea , Criança , Pré-Escolar , Seguimentos , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressão/efeitos adversos , Estimativa de Kaplan-Meier , Irradiação Linfática/efeitos adversos , Muromonab-CD3/uso terapêutico , Agonistas Mieloablativos/uso terapêutico , Dosagem Radioterapêutica , Retratamento/efeitos adversos , Retratamento/métodos , Estudos Retrospectivos , Tiotepa/uso terapêutico , Condicionamento Pré-Transplante/efeitos adversos , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Adulto Jovem
13.
Eur J Haematol ; 2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-30465728

RESUMO

OBJECTIVE: Relapse following allogeneic hematopoietic stem cell transplantation (HSCT) is still linked to a poor prognosis. Mainly, donor's T-cells mediate the graft-versus-leukemia effect. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an inhibitory molecule which down-regulates T-cell activation. Single nucleotide polymorphism (SNP) in CTLA-4 may have an effect on immune response. METHODS: Eighty-eight children with acute leukemia and their donors were genotyped of CTLA-4 gene for rs231775. We searched for an association of CTLA-4 SNP with relapse and survival after allogeneic HSCT. RESULTS: We identified a significantly reduced relapse rate in children who received a transplant from a donor with the CTLA-4 genotypes AG or GG in comparison to genotype AA of rs231775 (19% versus 40%, P =.026). In addition, we observed a significant difference in event-free survival (EFS) depending on the donor's genotype. The EFS was 70% or 46% if the patient was transplanted from a donor with CTLA-4 genotype AG/GG or AA, respectively (P =.025). In multivariate analysis, CTLA-4 genotype was an independent risk factor for relapse rate (P = .028). CONCLUSION: This study suggests that CTLA-4 polymorphism rs231775 is relevant for relapse and survival after allogeneic HSCT in childhood and should be further investigated in clinical trials. This article is protected by copyright. All rights reserved.

14.
Haematologica ; 2018 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-30093401

RESUMO

Despite intensified salvage treatments, children with relapsed/refractory acute myeloid leukemia have poor survival. We evaluated Gemtuzumab Ozogamicin (CD33-targeted drug) used on compassionate basis in patients diagnosed from 1995 until 2014 within Acute Myeloid Leukemia-Berlin-Frankfurt-Munster studies and identified 76 patients (<18 years) with highly-advanced and pretreated acute myeloid leukemia [refractory de novo acute myeloid leukemia (n=10), de novo acute myeloid leukemia refractory to relapse (1st early: n=41; 1st late: n=10; 2nd or more: n=10), and secondary acute myeloid leukemia (n=5)]. At doses of 2.5-10 mg/m,2, Gemtuzumab Ozogamicin was administered in 1-4 cycles as single agent (47%), combined with cytarabine (47%), or others (6%). Most common grade 3/4 adverse events were infections or febrile neutropenia (78% of severe adverse events), infusion-related immunologic reactions (6%), and gastrointestinal symptoms (5%). Three patients experienced veno-occlusive disease (one fatal due to exacerbation of a preexisting cardiomyopathy). Sixty-four percent received subsequent hematopoietic stem cell transplantation. Probability of 4-year overall survival was 18±5% in all, 27±7% in patients with and 0% in patients without hematopoietic stem cell transplantation (p<0.0001). Administration of Gemtuzumab Ozogamicin on a patient-specific, compassionate use basis was frequently considered in our study group and proved to be effective for bridging children with very advanced AML to hematopoietic stem cell transplantation. Uniform prospective studies for these patients are urgently needed.

15.
Br J Haematol ; 183(1): 104-109, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30028016

RESUMO

Osteonecrosis (ON) was prospectively assessed in 557 children and adolescents in the Berlin-Frankfurt-Münster Stem Cell Transplantation in children with acute lymphoblastic leukaemia 2003 trial. Median age at haematopoietic stem cell transplantation (HSCT) was 10·3 years (range 0·5-26). Cumulative incidence of symptomatic ON (sON) was 9% at 5 years (standard deviation 1%), median time from HSCT to diagnosis of sON was 12·4 months (range 1-126). Multivariate analysis identified age at HSCT [10-15 years vs. <10 years: hazard ratio (HR) 3·73, P = 0·009; >15 years vs. <10 years: HR 5·46, P = 0·001], diagnosis of sON prior to HSCT and chronic graft-versus-host disease (yes versus no: HR 2·696, P = 0·015) as significant independent risk factors for the development of sON.

17.
Biol Blood Marrow Transplant ; 24(5): 1005-1012, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29307718

RESUMO

Pediatric patients with refractory or relapsed metastatic neuroblastoma (NBL) have a poor prognosis despite autologous stem cell transplantation (SCT). Allogeneic SCT from a haploidentical donor has a remarkable alloreactive effect in patients with leukemia; thus, we evaluated this approach in children with very high-risk NBL. We analyzed data from 2 prospective phase I/II trials. A total of 26 patients with refractory (n = 5), metastatic relapsed (n = 20), or locally relapsed MYCN-positive (n = 1) NBL received a median of 17 × 106/kg T/B cell-depleted CD34+ stem cells with 68 × 103/kg residual T cells and 107 × 106/kg natural killer cells. The conditioning regimen comprised melphalan, fludarabine, thiotepa, OKT3, and a short course of mycophenolate mofetil post-transplantation. Engraftment occurred in 96% of the patients. Event-free survival and overall survival at 5 years were 19% and 23%, respectively. No transplantation-related mortality was observed, and the single death was due to progression/subsequent relapse. The median duration of follow-up was 8.1 years. Patients in complete remission before SCT had a significantly better prognosis than those with residual tumor load (P < .01). All patients with progressive disease before SCT relapsed within 1 year. Grade II and grade III acute graft-versus-host disease (GVHD) occurred in 31% and 12% of the patients, respectively. Chronic limited and extensive GVHD occurred in 28% and 10%, respectively. Our data indicate that haploidentical SCT is a feasible treatment option that can induce long-term remission in some patients with NBL with tolerable side effects, and may enable the development of further post-transplantation therapeutic strategies based on the donor-derived immune system.

18.
J Cancer Res Clin Oncol ; 144(3): 587-592, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29335768

RESUMO

PURPOSE: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative approach for a variety of hematological diseases; however, it is still associated with substantial morbidity and mortality. Transplant-related mortality (TRM) after HSCT depends mainly on the toxicity of the conditioning regimen, infections, and graft-versus-host disease. The purpose of this study was to identify the association between CTLA-4 single nucleotide polymorphisms and TRM in children undergoing allogeneic HSCT. METHODS: 153 donors and 153 children with acute lymphoblastic leukemia, acute myeloid leukemia or juvenile myelomonocytic leukemia who had undergone allogeneic HSCT were genotyped of CTLA-4 gene for rs3087243 (CT60G>A), rs231775 (+ 49 A>G) and rs4553808 using TaqMan real-time polymerase chain reaction. RESULTS: We observed a significant association between the donor's CLTA-4 genotype of rs3087243 and TRM in children undergoing allogeneic HSCT. Genotype AG was found in 78 donors (51%), GG in 44 donors (29%) and 31 donors (20%) were homozygous for AA. 30 patients died as a result of transplant-related causes. Interestingly, we observed a significantly reduced TRM in children who were transplanted from a donor with the CTLA-4 genotype GG in comparison to genotype AG or AA (9 versus 19 versus 36%, P = 0.013). In addition, we found significant differences of event-free survival (EFS) depending on the donor's genotype. The EFS was 64, 46 or 32% if the patient was transplanted from a donor with CTLA-4 genotype GG, AG or AA, respectively (P = 0.043). In multivariate analysis, CTLA-4 genotype of rs3087243 was an independent risk factor for TRM (P = 0.011) and EFS (P = 0.035). CONCLUSION: This study provides first evidence that the CTLA-4 polymorphisms are significant risk factors for TRM and survival in children undergoing allogeneic HSCT and should be evaluated in further trials.


Assuntos
Antígeno CTLA-4/genética , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia/mortalidade , Leucemia/terapia , Polimorfismo de Nucleotídeo Único , Doadores de Tecidos , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Genótipo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia/genética , Masculino , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/mortalidade
19.
Eur J Pediatr Surg ; 28(6): 477-483, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28946164

RESUMO

BACKGROUND: The incidence of invasive aspergillosis (IA) in children with hematooncological malignancies is increasing as a result of intensive treatment, immunosuppression, and extended use of broad-spectrum antibiotics. Infection of the GI tract by Aspergillus spp. is a rare and fatal complication, which often requires surgical diagnostic and therapeutic exploration. OBJECTIVE: The aim of this study was to determine the characteristics of symptomatic intestinal aspergillosis, diagnosis, treatment, and outcome of pediatric patients with an underlying hemato-oncologic disease. PATIENTS AND METHODS: We analyzed 2,307 German patients with acute lymphoblastic leukemia (ALL) from age 1 to 17 years registered in the AIEOP-BFM ALL 2000 study from 2000 to 2006. All reported adverse events were assessed for symptoms of IA and retrospectively reviewed for any sign or proof of intestinal involvement of IA. RESULTS: In this cohort, IA was reported in 30 of 2,307 patients while intestinal involvement was documented in five patients. Four of these patients had intestinal symptoms and three patients underwent explorative laparotomy. Among clinical cases with IA, gastrointestinal manifestation of IA mostly occurred in adolescent patients (10-16 years). Symptoms varied from abdominal tenderness and pain to constipation. Intestinal aspergillosis was proven by microbiological and histopathological examination and fungal infection was observed macroscopically in the jejunal lumen during surgery. Despite the extended surgery and antifungal therapy, outcome of disseminated IA with intestinal involvement remains poor. CONCLUSION: Surgeons should be aware of surgical complications of intestinal aspergillosis in children with hematooncological diseases requiring exploration and resection. IA is a rare event and still difficult to diagnose due to unspecific abdominal symptoms. Thus, biopsy sampling is of utmost importance to ensure diagnosis, and resection of necrotic or perforated tissue should be attempted early.


Assuntos
Aspergilose/cirurgia , Enteropatias/cirurgia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adolescente , Aspergilose/diagnóstico , Aspergilose/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Enteropatias/diagnóstico , Enteropatias/etiologia , Masculino , Estudos Retrospectivos , Resultado do Tratamento
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