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1.
Int J Cancer ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31407318

RESUMO

Immigration in Europe has increased considerably over the past decades with the immigrant population similarly expanding in Finland. Our aim was to study childhood cancer mortality and survival in immigrants. In all, 4,437 patients diagnosed with cancer under the age of 20 years between 1990 and 2009 were identified from the Finnish Cancer Registry and their parents from the Population Register Center. Information on demographic factors was obtained from Statistics Finland. Poisson regression modeling was used to estimate hazard ratios (HRs) for cancer deaths. The life table method and the log rank test were used in survival analysis. Patients or parents of foreign background and born abroad had higher 5-year mortality (patient HR 2.03, 95% CI 1.18-3.49; maternal HR 2.11, 95% CI 1.46-3.04; paternal HR 1.85, 95% CI 1.29-2.66) compared to those of Finnish background and born in Finland. Childhood cancer survival in 5-year follow-up was higher if the mother (83% vs. 68%) or the father (83% vs. 70%) were of Finnish background and born in Finland. Despite equal access to public health care, we observed significant differences in childhood cancer mortality and survival by background. Cultural differences, linguistic obstacles and difficulties in navigating the health care system may contribute, along with genetic and biologic factors. Offering tailored information and taking cultural and linguistic aspects into account is necessary when diagnosing and treating patients from different ethnic backgrounds who have not yet integrated into the local culture and health care system.

2.
Infect Dis (Lond) ; 51(10): 772-778, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31380705

RESUMO

Background: Viral infections are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Although immune suppression plays a central role, the literature shows conflicting results on interplay between post-transplant immune reconstitution (IR) and viral infections. Methods: We prospectively studied viral infections and IR in 30 pediatric patients undergoing allogenic HSCT, with a follow-up time of 24 months. In total, 1337 blood (CMV, EBV, HHV-6, ADV and BKV) and urine (BKV and JCV) virus samples were analyzed. IR including B-cells (CD19+), T cells (CD3+, CD4+, CD8+) and NK-cells were measured. Clinical outcomes included overall survival (OS), non-relapse mortality (NRM), graft-versus-host disease (GVHD) and occurrence of blood culture positive bacterial infections. Results: We found BKV reactivation to be most frequent, 47% of the children had viremia and 77% viruria. The frequencies of CMV, HHV-6 and adeno viremia were 37%, 37% and 6%, respectively. Viremias beyond 3 months post-HSCT were uncommon. Factors such as GVHD, use of steroids, EBV and CMV infections and pre-transplant irradiation affected IR. No specific viral infection or IR related factor was associated to OS or NRM. Conclusions: Viral infections and IR interact in a bi-directional manner. Accordingly, close follow-up of both IR and viral loads is warranted.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31449329

RESUMO

INTRODUCTION: The purpose of this study was to investigate the epidemiology and characteristics of surgically treated ovarian lesions in preadolescent girls. MATERIAL AND METHODS: This was a retrospective cohort study including all 0- to 11-year-old girls operated at a single center from 1999 to 2016 for ovarian cysts, neoplasms or torsions. Patient charts were reviewed for symptoms, preoperative radiological imaging, operative details and histopathology. RESULTS: We identified 78 girls, resulting in a population-based incidence of 4.2/100 000. Infants (n = 44) presented with benign cysts (42/44, 95%, one bilateral), a benign neoplasm (1/44, 2%) and a torsion without other pathology (1/44, 2%). Torsion was found in 25/29 (86%) ovaries with complex cysts and in 3/15 (21%) ovaries with simple cysts in preoperative imaging (P < 0.001). Most infants were symptomless. Lesions in 1- to 11-year-old girls (n = 34) included benign neoplasms (n = 21/34, 62%), malignant neoplasms (n = 5/34, 15%), a cyst with torsion (n = 1/34, 3%) and torsions without other pathology (n = 7/34, 21%). Torsion was more common in benign (17/21, 81%) than in malignant neoplasms (1/5, 20%) (P < 0.020). Ovarian diameter did not differ between ovaries with or without torsion (P = 0.238) or between benign and malignant neoplasms (P = 0.293). The duration of symptoms in lesions with or without torsion was similar. CONCLUSIONS: The majority of surgically treated ovarian lesions in preadolescent are benign lesions with torsion. Surgery should be ovary-preserving and performed without delay.

4.
J Med Genet ; 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413121

RESUMO

BACKGROUND: Metaphyseal dysplasia without hypotrichosis (MDWH) is a rare form of chondrodysplasia with no extraskeletal manifestations. MDWH is caused by RMRP mutations, but it is differentiated from the allelic condition cartilage-hair hypoplasia (CHH), which in addition to chondrodysplasia is characterised by thin hair, immunodeficiency and increased risk of malignancy. The long-term outcome of MDWH remains unknown. OBJECTIVE: We diagnosed severe agranulocytosis in a subject with RMRP mutations and normal hair. Based on this observation, we hypothesised that MDWH may, similar to CHH, associate with immune deficiency and malignancy. METHODS: We collected clinical and laboratory data for a cohort of 80 patients with RMRP mutations followed for over 30 years and analysed outcome data for those with features consistent with MDWH. RESULTS: In our cohort, we identified 10 patients with skeletal but no extraskeletal features during preschool age. Eight of these patients developed malignancy or clinically significant immunodeficiency during follow-up. Two of them died during chemotherapy for malignancy. At the time of the first extraskeletal manifestation, patients were school aged, 20, 43 and 50 years old. Laboratory signs of immunodeficiency (impaired lymphocyte proliferative responses) were demonstrated in four patients before the onset of symptoms. The patient outside this cohort, who had RMRP mutations, skeletal dysplasia, normal hair and severe agranulocytosis at 18 years of age, underwent haematopoietic stem cell transplantation. CONCLUSIONS: MDWH can present with severe late-onset extraskeletal manifestations and thus should be reclassified and managed as CHH.

5.
Front Immunol ; 10: 1581, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379817

RESUMO

Cartilage-hair hypoplasia (CHH) is a skeletal dysplasia with combined immunodeficiency, variable clinical course and increased risk of malignancy. Management of CHH is complicated by a paucity of long-term follow-up data, as well as knowledge on prognostic factors. We assessed clinical course and risk factors for mortality in a prospective cohort study of 80 patients with CHH recruited in 1985-1991 and followed up until 2016. For all patients we collected additional health information from health records and from the national Medical Databases and Cause-of-death Registry. The primary outcome was immunodeficiency-related death, including death from infections, lung disease and malignancy. Standardized mortality ratios (SMRs) were calculated using national mortality rates as reference. Half of the patients (57%, n = 46) manifested no symptoms of immunodeficiency during follow-up while 19% (n = 15) and 24% (n = 19) demonstrated symptoms of humoral or combined immunodeficiency, including six cases of adult-onset immunodeficiency. In a significant proportion of patients (17/79, 22%), clinical features of immunodeficiency progressed over time. Of the 15 patients with non-skin cancer, eight had no preceding clinical symptoms of immunodeficiency. Altogether 20 patients had deceased (SMR = 7.0, 95%CI = 4.3-11); most commonly from malignancy (n = 7, SMR = 10, 95%CI = 4.1-21) and lung disease (n = 4, SMR = 46, 95%CI = 9.5-130). Mortality associated with birth length below -4 standard deviation (compared to normal, SMR/SMR ratio = 5.4, 95%CI = 1.5-20), symptoms of combined immunodeficiency (compared to asymptomatic, SMR/SMR ratio = 3.9, 95%CI = 1.3-11), Hirschsprung disease (odds ratio (OR) 7.2, 95%CI = 1.04-55), pneumonia in the first year of life or recurrently in adulthood (OR = 7.6/19, 95%CI = 1.3-43/2.6-140) and autoimmunity in adulthood (OR = 39, 95%CI = 3.5-430). In conclusion, patients with CHH may develop adult-onset immunodeficiency or malignancy without preceding clinical symptoms of immune defect, warranting careful follow-up. Variable disease course and risk factors for mortality should be acknowledged.

6.
Cancer ; 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31287570

RESUMO

BACKGROUND: Childhood cancer survivors have been reported to be vulnerable to psychiatric morbidities and risky health behavior. Suicides, substance abuse, accidents, and violence as causes of death can be regarded as an extreme manifestation of risky health behavior. In the current study, the authors studied the risk of suicide and other risky health behavior-related deaths among childhood cancer patients in Denmark, Finland, and Sweden. METHODS: Using linkage between national cancer, population, and cause-of-death registries, the authors investigated the causes of death in 29,285 patients diagnosed with cancer before age 20 years between 1971 and 2009 compared with a cohort of 146,282 age-matched, sex-matched, and country-matched population comparisons. Rate ratios (RRs) with 95% CIs were estimated using Poisson regression models, adjusting for demographic factors. RESULTS: The overall risk of dying of a risky health behavior was found to be increased among childhood cancer patients (RR, 1.25; 95% CI, 1.06-1.47) when compared with population comparisons. The elevated risk was statistically significant among patients with central nervous system tumors (RR, 1.49; 95% CI, 1.08-2.05) and patients diagnosed at ages 5 to 9 years and 15 to 19 years (RR, 1.50 [95% CI, 1.01-2.24] and RR, 1.31 [95% CI, 1.03-1.67], respectively). The overall risk of suicide was found to be increased (RR, 1.37; 95% CI, 1.02-1.83), and statistically significantly so when patients were diagnosed between ages 15 and 19 years (RR, 1.61; 95% CI, 1.09-2.39). CONCLUSIONS: Childhood cancer patients appear to have an increased risk of risky health behavior-related causes of death compared with the general population. The results of the current study suggest the importance of integrating psychosocial support into the follow-up care of these individuals.

7.
BMC Infect Dis ; 19(1): 404, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077135

RESUMO

BACKGROUND: Symptomatic primary Epstein-Barr virus infection is a usually self-limiting illness in adolescents. We present a case of an adolescent who had been receiving azathioprine for inflammatory bowel disease for four years and developed a life-threatening primary Epstein-Barr virus infection successfully treated with rituximab. CASE PRESENTATION: An 11-year-old girl presented with chronic, bloody diarrhea. Endoscopic biopsies confirmed a diagnosis of chronic ulcerative colitis with features of Crohn's disease. Azathioprine was initiated after one year due to active colitis. She responded well and remission was achieved. At the age of 16 years she developed a life-threatening Epstein-Barr virus infection including severe multiple organ failure and was critically ill for 4 weeks in the intensive care unit. Natural killer cells were virtually absent in the lymphocyte subset analysis. Azathioprine was stopped on admission. She was initially treated with corticosteroids, acyclovir and intravenous immunoglobulin. Approximately 30 days after admission, she developed signs of severe hepatitis and pneumonitis and received weekly rituximab infusions for 8 weeks. Primary immunodeficiency was excluded by whole exome sequencing in two independent laboratories. Persistent viremia stopped when the natural killer cell count started to rise, approximately 90 days after the cessation of azathioprine. CONCLUSIONS: We found 17 comparable cases in the literature. None of the previous cases reported in the literature, who had been treated with azathioprine and developed either a severe or a fatal Epstein-Barr virus infection, underwent full genetic and prospective immunological workup to rule out known primary immunodeficiencies. Recently, azathioprine has been shown to cause rather specific immunosuppression, resulting in natural killer cell depletion. Our case demonstrates that slow recovery from azathioprine-induced natural killer cell depletion, 3 months after the stopping of azathioprine, coincided with the clearance of viremia and clinical recovery. Finally, our choice of treating the patient with rituximab, as previously used for patients with a severe immunosuppression and Epstein-Barr virus viremia, appeared to be successful in this case. We suggest testing for Epstein-Barr virus serology before starting azathioprine and measuring natural killer cell counts during the treatment to identify patients at risk of developing an unusually severe primary Epstein-Barr virus infection.


Assuntos
Azatioprina/efeitos adversos , Infecções por Vírus Epstein-Barr/etiologia , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/complicações , Células Matadoras Naturais , Azatioprina/uso terapêutico , Biópsia , Criança , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/imunologia , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Células Matadoras Naturais/efeitos dos fármacos , Contagem de Linfócitos , Estudos Prospectivos , Rituximab/uso terapêutico , Resultado do Tratamento
8.
Front Immunol ; 9: 2468, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30410491

RESUMO

Background: Mutations in RMRP, encoding a non-coding RNA molecule, underlie cartilage-hair hypoplasia (CHH), a syndromic immunodeficiency with multiple pathogenetic mechanisms and variable phenotype. Allergy and asthma have been reported in the CHH population and some patients suffer from autoimmune (AI) diseases. Objective: We explored AI and allergic manifestations in a large cohort of Finnish patients with CHH and correlated clinical features with laboratory parameters and autoantibodies. Methods: We collected clinical and laboratory data from patient interviews and hospital records. Serum samples were tested for a range of autoantibodies including celiac, anti-cytokine, and anti-21-hydroxylase antibodies. Nasal cytology samples were analyzed with microscopy. Results: The study cohort included 104 patients with genetically confirmed CHH; their median age was 39.2 years (range 0.6-73.6). Clinical autoimmunity was common (11/104, 10.6%) and included conditions previously undescribed in subjects with CHH (narcolepsy, psoriasis, idiopathic thrombocytopenic purpura, and multifocal motor axonal neuropathy). Patients with autoimmunity more often had recurrent pneumonia, sepsis, high immunoglobulin (Ig) E and/or undetectable IgA levels. The mortality rates were higher in subjects with AI diseases ( χ ( 2 ) 2 = 14.056, p = 0.0002). Several patients demonstrated serum autoantibody positivity without compatible symptoms. We confirmed the high prevalence of asthma (23%) and allergic rhinoconjunctivitis (39%). Gastrointestinal complaints, mostly persistent diarrhea, were also frequently reported (32/104, 31%). Despite the history of allergic rhinitis, no eosinophils were observed in nasal cytology in five tested patients. Conclusions: AI diseases are common in Finnish patients with CHH and are associated with higher mortality, recurrent pneumonia, sepsis, high IgE and/or undetectable IgA levels. Serum positivity for some autoantibodies was not associated with clinical autoimmunity. The high prevalence of persistent diarrhea, asthma, and symptoms of inflammation of nasal mucosa may indicate common pathways of immune dysregulation.

9.
Orphanet J Rare Dis ; 13(1): 139, 2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-30115091

RESUMO

BACKGROUND: The telomere biology disorders (TBDs) include a range of multisystem diseases characterized by mucocutaneous symptoms and bone marrow failure. In dyskeratosis congenita (DKC), the clinical features of TBDs stem from the depletion of crucial stem cell populations in highly proliferative tissues, resulting from abnormal telomerase function. Due to the wide spectrum of clinical presentations and lack of a conclusive laboratory test it may be challenging to reach a clinical diagnosis, especially if patients lack the pathognomonic clinical features of TBDs. METHODS: Clinical sequencing was performed on a cohort of patients presenting with variable immune phenotypes lacking molecular diagnoses. Hypothesis-free whole-exome sequencing (WES) was selected in the absence of compelling diagnostic hints in patients with variable immunological and haematological conditions. RESULTS: In four patients belonging to three families, we have detected five novel variants in known TBD-causing genes (DKC1, TERT and RTEL1). In addition to the molecular findings, they all presented shortened blood cell telomeres. These findings are consistent with the displayed TBD phenotypes, addressing towards the molecular diagnosis and subsequent clinical follow-up of the patients. CONCLUSIONS: Our results strongly support the utility of WES-based approaches for routine genetic diagnostics of TBD patients with heterogeneous or atypical clinical presentation who otherwise might remain undiagnosed.

10.
Thromb Haemost ; 118(8): 1390-1396, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29960273

RESUMO

Coagulation system is disturbed by several mechanisms after allogeneic haematopoietic stem cell transplantation (HSCT). We evaluated the effect of HSCT on coagulation system by various conventional and investigational methods in 30 children and adolescents who received HSCT due to haematological malignancies. Pro-thrombin fragment 1 + 2, a specific measure of thrombin generation, and von Willebrand factor, a measure of endothelial activation, increased after conditioning treatment, and remained elevated until 3 months after HSCT (p < 0.05 for all comparisons to pre-conditioning treatment). D-dimer, a measure of fibrin turnover, was elevated from the second week onwards until 4 weeks after HSCT (p < 0.05). Endogenous thrombin potential was increased after conditioning, and at 2 weeks after HSCT (p < 0.05). Furthermore, the activities of acute phase reactants fibrinogen and coagulation factor VIII were increased (p < 0.05 for all comparisons to pre-conditioning treatment) from the first week onwards up to 3 weeks and 3 months after HSCT, respectively. Taken together, paediatric patients receiving HSCT demonstrate distinct and prolonged variations in the coagulation system towards a pro-coagulant state. This shift is of importance when estimating the risk of haemostatic and thrombotic complications in these children.

11.
J Pediatr Surg ; 2018 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-29887169

RESUMO

PURPOSE: To evaluate the association between Wilms tumor histology at diagnosis and the change in Wilms' tumor volume during preoperative chemotherapy. METHODS: We included all the 52 patients operated for Wilms tumor at 1988-2015, who had both pathology samples and either CT or MRI-images before and after preoperative chemotherapy, available for reevaluation. RESULTS: The median tumor volume was 586 ml (IQR 323-903) at diagnosis. The median change in tumor volume was -68% (IQR -85 to -40, p < 0.001) and the proportion of tumor necrosis 85% (IQR 24-97), after preoperative chemotherapy. There was a correlation between blastemal cell content in prechemotherapy cutting needle biopsy (CNB) sample and the reduction in tumor volume (Rho = -0.452, p = 0.002). High stromal and epithelial cell contents in CNB samples were associated with the lesser change in tumor volume (Rho = 0.279, p  =0.053 and Rho = 0.300, p = 0.038 respectively). Reduction of tumor volume and the proportion of tumor necrosis after chemotherapy were associated (Rho = -0.502, p < 0.001). The actual viable tumor volume decreased in median by 97% (IQR 65-100), and the decrease could be seen in all cellular components. In three patients, the tumor volume increased more than 10% during the preoperative chemotherapy. Two of them had anaplastic tumor in the nephrectomy specimen. CONCLUSION: Wilms tumor total and viable tumor volumes were reduced by 68% and 97% with preoperative chemotherapy, respectively. High proportion of blastemal cells in CNB was associated with greatest decrease in Wilms tumor volume. Increase in tumor volume during preoperative chemotherapy may indicate anaplastic tumor and prolonging of preoperative therapy should be avoided. TYPE OF STUDY: Retrospective review. LEVEL OF EVIDENCE: Level III.

12.
Acta Oncol ; 57(11): 1547-1555, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29863418

RESUMO

INTRODUCTION: Parental socioeconomic status has been proposed to have an influence on childhood cancer mortality even in high-income countries. Our study investigated the influence of parental socioeconomic factors on childhood cancer mortality. MATERIAL AND METHODS: We identified 4437 patients diagnosed with cancer under the age of 20 from 1990 to 2009 and their parents from the Finnish cancer and central population registers. Information on death from primary cancer during five-year follow-up and parental socioeconomic factors was obtained from Statistics Finland. Poisson regression modeling was used to estimate hazard ratios (HRs) for factors related to cause-specific mortality and recursive tree based survival analysis to identify important risk factors and interactions. RESULTS: Mortality was lower in the highest quartile of combined parental disposable income (HR 0.68, CI 95% 0.52-0.89) compared to the lowest quartile. In the most recent diagnostic period from 2000 to 2009, highest attained education of either parent being post-secondary predicted lower mortality (HR 0.73, CI 95% 0.60-0.88) compared to parents who had attained primary or lower education. CONCLUSION: Despite high quality public health care and comprehensive social security, both high parental income and education were associated with lower mortality after childhood cancer. Lower health literacy and financial pressures limiting treatment adherence may explain higher mortality in children with less educated parents and parents with lower income. Motivation and support during treatment and follow-up period is needed concerning the families of these patients.

14.
J Pediatr Hematol Oncol ; 40(1): e13-e18, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29200159

RESUMO

Posterior reversible encephalopathy syndrome (PRES) in children with acute lymphoblastic leukemia has been increasingly recognized as a clinicoradiological entity. Our aim was to describe the incidence of PRES in pediatric patients with ALL, identify its risk factors, and examine its prognostic importance. For this research, we conducted a systematic, retrospective review of the patient records in a population-based series of children with acute lymphoblastic leukemia (n=643) treated in Finland from 1992 to 2008. Of the patients with ALL, 4.5% (n=29) developed radiologically confirmed PRES, of which 28 cases occurred during induction. Hypertension (P=0.006; odds ratio [OR], 4.10, confidence interval [CI], 1.50-11.25), constipation (P=0.001; OR, 5.60; CI, 2.02-15.52), and >14 days of alkalinization (P=0.017; OR, 3.27; CI, 1.23-8.68) were significant independent risk factors for PRES. One-third of the patients developed epilepsy. Relapses occurred significantly more often in those patients with PRES (P=0.001), which was associated with worse overall survival (P=0.040; 5-year survival=75.9% [60.3%-91.4%] vs. 88.4% [85.8%-90.9%]). Using NOPHO-ALL 92/2000 protocols, PRES is a significant early complication of therapy in ALL, and was associated with a poorer prognosis and significant neurological morbidity.


Assuntos
Síndrome da Leucoencefalopatia Posterior/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adolescente , Criança , Pré-Escolar , Epilepsia/etiologia , Feminino , Finlândia/epidemiologia , Humanos , Hipertensão/etiologia , Incidência , Quimioterapia de Indução/efeitos adversos , Lactente , Masculino , Síndrome da Leucoencefalopatia Posterior/epidemiologia , Síndrome da Leucoencefalopatia Posterior/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Convulsões/etiologia , Análise de Sobrevida
15.
J Pediatr Surg ; 53(8): 1611-1614, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29074135

RESUMO

PURPOSE: To evaluate usefulness of cutting needle biopsy (CNB) to recognize pediatric renal tumors and to predict the evolution of histology during preoperative chemotherapy of Wilms tumors. METHODS: Ninety pediatric patients were operated for renal tumors at our institution in 1988-2015. We included all 64 patients who had undergone CNB at diagnosis and whose CNB and nephrectomy samples were available for re-evaluation. RESULTS: The CNB was diagnostic in all 59 Wilms tumors but only in two out of five non-Wilms tumors. Anaplasia was missed by CNB in one of three with diffuse anaplasia in nephrectomy specimens. In Wilms tumors the proportions of the blastemal, stromal and epithelial components were 55% (IQR 25-85), 28% (IQR 10-58) and 2% (IQR 0-10) in CNB samples and 5% (IQR 0-64), 15% (IQR 0-50) and 15% (IQR 0-44) in the nephrectomy specimens (p-values 0.002, 0.599 and 0.005 respectively). The degree of tumor necrosis was in median 80% (IQR 21-97), after preoperative chemotherapy. The degree of tumor necrosis after chemotherapy had a positive correlation with the proportion of blastemal component (p=0.008) and a negative correlation with proportion of epithelial component in pre-chemotherapy CNB samples (p<0.001). CONCLUSIONS: Wilms tumors are usually recognizable unlike non-Wilms tumors in CNB at diagnosis. In Wilms tumors, high blastemal cell content is associated with significant tumor necrosis during pre-operative chemotherapy. Our results do not support routine use of CNB in diagnosis of renal tumors. TYPE OF STUDY: Retrospective review. LEVEL OF EVIDENCE: Level III.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Tumor de Wilms/tratamento farmacológico , Tumor de Wilms/patologia , Antineoplásicos/uso terapêutico , Biópsia por Agulha , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Nefrectomia/métodos , Estudos Retrospectivos
16.
J Allergy Clin Immunol ; 141(1): 322-328.e10, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28392333

RESUMO

BACKGROUND: Rare DNA breakage repair disorders predispose to infection and lymphoreticular malignancies. Hematopoietic cell transplantation (HCT) is curative, but coadministered chemotherapy or radiotherapy is damaging because of systemic radiosensitivity. We collected HCT outcome data for Nijmegen breakage syndrome, DNA ligase IV deficiency, Cernunnos-XRCC4-like factor (Cernunnos-XLF) deficiency, and ataxia-telangiectasia (AT). METHODS: Data from 38 centers worldwide, including indication, donor, conditioning regimen, graft-versus-host disease, and outcome, were analyzed. Conditioning was classified as myeloablative conditioning (MAC) if it contained radiotherapy or alkylators and reduced-intensity conditioning (RIC) if no alkylators and/or 150 mg/m2 fludarabine or less and 40 mg/kg cyclophosphamide or less were used. RESULTS: Fifty-five new, 14 updated, and 18 previously published patients were analyzed. Median age at HCT was 48 months (range, 1.5-552 months). Twenty-nine patients underwent transplantation for infection, 21 had malignancy, 13 had bone marrow failure, 13 received pre-emptive transplantation, 5 had multiple indications, and 6 had no information. Twenty-two received MAC, 59 received RIC, and 4 were infused; information was unavailable for 2 patients. Seventy-three of 77 patients with DNA ligase IV deficiency, Cernunnos-XLF deficiency, or Nijmegen breakage syndrome received conditioning. Survival was 53 (69%) of 77 and was worse for those receiving MAC than for those receiving RIC (P = .006). Most deaths occurred early after transplantation, suggesting poor tolerance of conditioning. Survival in patients with AT was 25%. Forty-one (49%) of 83 patients experienced acute GvHD, which was less frequent in those receiving RIC compared with those receiving MAC (26/56 [46%] vs 12/21 [57%], P = .45). Median follow-up was 35 months (range, 2-168 months). No secondary malignancies were reported during 15 years of follow-up. Growth and developmental delay remained after HCT; immune-mediated complications resolved. CONCLUSION: RIC HCT resolves DNA repair disorder-associated immunodeficiency. Long-term follow-up is required for secondary malignancy surveillance. Routine HCT for AT is not recommended.

17.
Duodecim ; 133(3): 251-8, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29205023

RESUMO

Graft-versus-host disease (GvHD) remains a major treatment-related risk in patients undergoing stem cell transplantation. Although advances in HLA-typing and graft types have reduced the risk of GvHD, a breakthrough in the treatment of severe GvHD is still lacking. Allogenic stem cell transplant has potentially beneficial immunological effects on the malignant disease necessitating transplantation, and the importance of these effects must be considered when treating GvHD.


Assuntos
Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco , Humanos , Fatores de Risco
18.
Blood ; 130(24): 2682-2688, 2017 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-28974505

RESUMO

Deficiency of adenosine deaminase 2 (DADA2) is caused by biallelic deleterious mutations in CECR1 DADA2 results in variable autoinflammation and vasculopathy (recurrent fevers, livedo reticularis, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency and bone marrow failure. Tumor necrosis factor-α blockade is the treatment of choice for the autoinflammation and vascular manifestations. Hematopoietic stem cell transplantation (HSCT) represents a potential definitive treatment. We present a cohort of 14 patients from 6 countries who received HSCT for DADA2. Indication for HSCT was bone marrow dysfunction or immunodeficiency. Six of 14 patients had vasculitis pre-HSCT. The median age at HSCT was 7.5 years. Conditioning regimens were myeloablative (9) and reduced intensity (5). Donors were HLA-matched sibling (n = 1), HLA-matched unrelated (n = 9), HLA-mismatched unrelated (n = 3), and HLA haploidentical sibling (n = 1). All patients are alive and well with no new vascular events and resolution of hematological and immunological phenotype at a median follow-up of 18 months (range, 5 months to 13 years). Plasma ADA2 enzyme activity normalized in those tested post-HSCT (7/7), as early as day +14 (myeloid engraftment). Post-HSCT hematological autoimmunity (cytopenias) was reported in 4 patients, acute graft-versus-host disease grade 1 in 2, grade 2 in 3, and grade 3-4 in 1, and moderate chronic graft-versus-host disease in 1 patient. In conclusion, in 14 patients, HSCT was an effective and definitive treatment of DADA2.


Assuntos
Adenosina Desaminase/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/terapia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Mutação , Adenosina Desaminase/sangue , Adenosina Desaminase/metabolismo , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Síndromes de Imunodeficiência/enzimologia , Lactente , Recém-Nascido , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Fenótipo , Condicionamento Pré-Transplante/métodos
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