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2.
Br J Haematol ; 187(5): 559-562, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31309539
3.
Clin Adv Hematol Oncol ; 17(2): 122-131, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30845115

RESUMO

Langerhans cell histiocytosis (LCH) is an inflammatory neoplasm of myeloid origin characterized by the presence of classic CD1a+/CD207+ cells. An ongoing debate over the grouping of LCH was finally settled in favor of neoplasm after the discovery of the BRAF V600E mutation in 2010. The pathologic cells were found to involve an almost universal activation of the MAPK/ERK pathway, with mutations identified in most kinases upstream of ERK (RAS/RAF/MEK). The clinical presentation of LCH is a mixed bag, ranging from self-resolving localized disease to fulminant, fatal disseminated disease. The current standard of care for patients with multisystem LCH, who have high relapse rates, continues to be combination treatment with vinblastine and prednisone. Patients treated with BRAF and MEK inhibitors have shown a significant and sustained response in early-phase trials. During the current decade, researchers have described an extensive genomic landscape for LCH that has significantly enlarged our understanding of the biology and pathogenesis of this disease, especially neurodegenerative LCH. These advances have opened the door to studies of precision medicine and targeted therapy in LCH. Disease reactivation, long-term sequelae, very high-risk disease, and neurodegenerative LCH represent ongoing challenges. A renewed understanding of the biology of this disease, coupled with targeted therapies, may help in overcoming most of these challenges.


Assuntos
Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/terapia , Biomarcadores , Criança , Gerenciamento Clínico , Suscetibilidade a Doenças , Histiocitose de Células de Langerhans/etiologia , Histiocitose de Células de Langerhans/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , Terapia de Alvo Molecular , Mutação , Fenótipo , Índice de Gravidade de Doença
4.
J Cancer Educ ; 2019 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-30739269

RESUMO

Videotaped information has been shown to be effective in reducing parental anxiety and facilitating knowledge transfer in various clinical settings. There is lack of literature on the use of videotaped information during the pediatric oncology initial family disclosure meeting. The purpose of this study was to deliver an informative DVD, highlighting information on childhood acute lymphoblastic leukemia (ALL), to parents of children with newly diagnosed ALL and to assess if the DVD provided increased levels of satisfaction and decreased levels of anxiety in parents around the time of diagnosis. We surveyed 24 parents of children on active treatment for ALL, diagnosed between the ages of 1 and 18 years from 2008 to 2016 at The Hospital for Sick Children, Toronto, Canada. Parents were provided a survey questionnaire assessing levels of satisfaction with information communicated by the healthcare team and anxiety following verbal disclosure and were asked to report satisfaction and anxiety levels immediately following viewing the DVD intervention. Twenty-three/24 (95.8%) parents surveyed reported seeking information from additional resources after disclosure. Of the 24 parents who watched the DVD, 12 (50.0%) watched it once, while 12 (50.0%) watched it twice or more. All parents were satisfied with DVD information, and there was a significant decrease in anxiety after viewing (P = 0.03). All 24 parents felt that the DVD was a useful educational tool. Videotaped information after verbal disclosure is an effective educational resource and is associated with reduced anxiety among parents of children with ALL.

5.
Cancer ; 125(6): 963-971, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30521100

RESUMO

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm characterized by the presence of abnormal CD1a-positive (CD1a+ )/CD207+ histiocytes. Hemophagocytic lymphohistiocytosis (HLH) represents a spectrum of hyperinflammatory syndromes typified by the dysregulated activation of the innate and adaptive immune systems. Patients with LCH, particularly those with multisystem (MS) involvement, can develop severe hyperinflammation mimicking that observed in HLH. Nevertheless, to the authors' knowledge, little is known regarding the prevalence, timing, risk factors for development, and outcomes of children and young adults who develop HLH within the context of MS-LCH (hereafter referred to LCH-associated HLH). METHODS: To gain further insights, the authors conducted a retrospective, multicenter study and collected data regarding all patients diagnosed with MS-LCH between 2000 and 2015. RESULTS: Of 384 patients with MS-LCH, 32 were reported by their primary providers to have met the diagnostic criteria for HLH, yielding an estimated 2-year cumulative incidence of 9.3% ± 1.6%. The majority of patients developed HLH at or after the diagnosis of MS-LCH, and nearly one-third (31%) had evidence of an intercurrent infection. Patient age <2 years at the time of diagnosis of LCH; female sex; LCH involvement of the liver, spleen, and hematopoietic system; and a lack of bone involvement each were found to be independently associated with an increased risk of LCH-associated HLH. Patients with MS-LCH who met the criteria for HLH had significantly poorer 5-year survival compared with patients with MS-LCH who did not meet the criteria for HLH (69% vs 97%; P < .0001). CONCLUSIONS: Given its inferior prognosis, further efforts are warranted to enhance the recognition and optimize the treatment of patients with LCH-associated HLH.


Assuntos
Sistema Hematopoético/imunologia , Histiocitose de Células de Langerhans/complicações , Fígado/imunologia , Linfo-Histiocitose Hemofagocítica/epidemiologia , Baço/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Sistema Hematopoético/patologia , Histiocitose de Células de Langerhans/imunologia , Humanos , Lactente , Recém-Nascido , Fígado/patologia , Linfo-Histiocitose Hemofagocítica/imunologia , Masculino , Prognóstico , Estudos Retrospectivos , Baço/patologia , Adulto Jovem
6.
Front Immunol ; 10: 3045, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31998317

RESUMO

Langerhans Cell Histiocytosis (LCH) is a neoplastic disorder of hematopoietic origin characterized by inflammatory lesions containing clonal histiocytes (LCH-cells) intermixed with various immune cells, including T cells. In 50-60% of LCH-patients, the somatic BRAF V600E driver mutation, which is common in many cancers, is detected in these LCH-cells in an otherwise quiet genomic landscape. Non-synonymous mutations like BRAF V600E can be a source of neoantigens capable of eliciting effective antitumor CD8+ T cell responses. This requires neopeptides to be stably presented by Human Leukocyte Antigen (HLA) class I molecules and sufficient numbers of CD8+ T cells at tumor sites. Here, we demonstrate substantial heterogeneity in CD8+ T cell density in n = 101 LCH-lesions, with BRAF V600E mutated lesions displaying significantly lower CD8+ T cell:CD1a+ LCH-cell ratios (p = 0.01) than BRAF wildtype lesions. Because LCH-lesional CD8+ T cell density had no significant impact on event-free survival, we investigated whether the intracellularly expressed BRAF V600E protein is degraded into neopeptides that are naturally processed and presented by cell surface HLA class I molecules. Epitope prediction tools revealed a single HLA class I binding BRAF V600E derived neopeptide (KIGDFGLATEK), which indeed displayed strong to intermediate binding capacity to HLA-A*03:01 and HLA-A*11:01 in an in vitro peptide-HLA binding assay. Mass spectrometry-based targeted peptidomics was used to investigate the presence of this neopeptide in HLA class I presented peptides isolated from several BRAF V600E expressing cell lines with various HLA genotypes. While the HLA-A*02:01 binding BRAF wildtype peptide KIGDFGLATV was traced in peptides isolated from all five cell lines expressing this HLA subtype, KIGDFGLATEK was not detected in the HLA class I peptidomes of two distinct BRAF V600E transduced cell lines with confirmed expression of HLA-A*03:01 or HLA-A*11:01. These data indicate that the in silico predicted HLA class I binding and proteasome-generated neopeptides derived from the BRAF V600E protein are not presented by HLA class I molecules. Given that the BRAF V600E mutation is highly prevalent in chemotherapy refractory LCH-patients who may qualify for immunotherapy, this study therefore questions the efficacy of immune checkpoint inhibitor therapy in LCH.

7.
J Pediatr Oncol Nurs ; 35(6): 406-416, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29950139

RESUMO

PURPOSE: Needle procedures are among the most distressing aspects of pediatric cancer-related treatment. Virtual reality (VR) distraction offers promise for needle-related pain and distress given its highly immersive and interactive virtual environment. This study assessed the usability (ease of use and understanding, acceptability) of a custom VR intervention for children with cancer undergoing implantable venous access device (IVAD) needle insertion. METHOD: Three iterative cycles of mixed-method usability testing with semistructured interviews were undertaken to refine the VR. RESULTS: Participants included 17 children and adolescents (8-18 years old) with cancer who used the VR intervention prior to or during IVAD access. Most participants reported the VR as easy to use (82%) and understand (94%), and would like to use it during subsequent needle procedures (94%). Based on usability testing, refinements were made to VR hardware, software, and clinical implementation. Refinements focused on increasing responsiveness, interaction, and immersion of the VR program, reducing head movement for VR interaction, and enabling participant alerts to steps of the procedure by clinical staff. No adverse events of nausea or dizziness were reported. CONCLUSIONS: The VR intervention was deemed acceptable and safe. Next steps include assessing feasibility and effectiveness of the VR intervention for pain and distress.


Assuntos
Ferimentos Penetrantes Produzidos por Agulha/terapia , Neoplasias/terapia , Manejo da Dor/métodos , Dor Processual/psicologia , Realidade Virtual , Adolescente , Criança , Feminino , Humanos , Masculino , Interface Usuário-Computador
8.
Blood ; 131(26): 2877-2890, 2018 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-29720485

RESUMO

Rosai-Dorfman-Destombes disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by accumulation of activated histiocytes within affected tissues. RDD, which now belongs to the R group of the 2016 revised histiocytosis classification, is a widely heterogeneous entity with a range of clinical phenotypes occurring in isolation or in association with autoimmune or malignant diseases. Recent studies have found NRAS, KRAS, MAP2K1, and ARAF mutations in lesional tissues, raising the possibility of a clonal origin in some forms of RDD. More than 1000 reports have been published in the English literature; however, there is a lack of consensus regarding approach for the clinical management of RDD. Although in most cases RDD can be observed or treated with local therapies, some patients with refractory or multifocal disease experience morbidity and mortality. Here we provide the first consensus multidisciplinary recommendations for the diagnosis and management of RDD. These recommendations were discussed at the 32nd Histiocyte Society Meeting by an international group of academic clinicians and pathologists with expertise in RDD. We include guidelines for clinical, laboratory, pathologic, and radiographic evaluation of patients with RDD together with treatment recommendations based on clinical experience and review of the literature.


Assuntos
Histiócitos/patologia , Histiocitose Sinusal/diagnóstico , Histiocitose Sinusal/terapia , Corticosteroides/uso terapêutico , Biópsia , Gerenciamento Clínico , Predisposição Genética para Doença , Histiócitos/metabolismo , Histiocitose Sinusal/genética , Histiocitose Sinusal/patologia , Humanos , Imunoterapia , Mutação , Guias de Prática Clínica como Assunto , Prognóstico , Radioterapia
9.
Mediterr J Hematol Infect Dis ; 10(1): e2018019, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29531656

RESUMO

Familial Mediterranean fever (FMF) has been associated with hematological malignancies but has not been reported in association with Hodgkin lymphoma (HL). We hereby describe the first pediatric patient with FMF and stage IIA nodular sclerosis HL. She was treated with prednisone, doxorubicin, vincristine and etoposide (OEPA) being on therapy with colchicine. However, she suffered more than expected treatment-related toxicity attributed either to chemotherapy (severe neutropenia) or colchicine (Abdominal pains and diarrhoea). Colchicine had to be discontinued. In the absence of colchicine, she tolerated very well the second cycle of chemotherapy. Currently, she is in remission at 17 months after her HL diagnosis, and her FMF is under control with colchicine without any signs of toxicity.

10.
Mediterr J Hematol Infect Dis ; 10(1): e2018020, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29531657

RESUMO

Background: The incidence and biology of non-Hodgkin lymphoma (NHL) vary according to age. Some data suggest that the impact of age in pediatric and adolescent NHL patients depends on the histological subtype. Objectives: We aimed to analyze the impact of age at diagnosis on clinical characteristics and treatment-related toxicity in children and adolescents with NHL. Methods: Retrospective review of medical records of children and adolescents diagnosed with NHL at the Hospital for Sick Children, Toronto, between January 1995 and December 2008. Results: 164 children were diagnosed with NHL during the study period, with a median age at diagnosis of 10 years. With a median follow-up of 6.2 years, 5-year OS in patients aged <15 and 15-18 years was 89± 2% vs 82% ± 6%, respectively (P = 0.30), and 5-year EFS was 84% ± 3% vs. 77% ± 7% (P= 0.37). In Burkitt's lymphoma (BL) and lymphoblastic lymphoma (LL) there was a trend towards better outcomes in children compared to adolescents, with EFS of 91% ± 4% vs. 75% ± 15%, respectively in BL (P= 0.17), and 82% ± 7% vs. 51.4% ± 2% respectively in LL (P= 0.16). Late effects occurred in 21 patients (12.8%). Conclusions: Children with NHL aged < 15 years tend to have better survival rates and similar long-term toxicity than adolescents aged 15-18 years.

11.
Pediatr Blood Cancer ; 65(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28944988

RESUMO

Central nervous system (CNS) involvement in Langerhans cell histiocytosis (LCH) can include mass lesions of the hypothalamic pituitary axis, choroid plexus, cerebrum, and cerebellum or magnetic resonance imaging (MRI) signal abnormalities of the cerebellum, pons, and basal ganglia. The term neurodegenerative (ND) CNS-LCH has been given to the MRI signal abnormalities and neurologic dysfunction, although initially patients may have no clinical symptoms. Standardized evaluations to better understand the natural history and response to therapy are needed. We propose guidelines for clinical, radiologic, and physiologic tests as a framework for developing the best methods of evaluation, which can then be tested in prospective treatment protocols.


Assuntos
Encéfalo/diagnóstico por imagem , Histiocitose de Células de Langerhans , Imagem por Ressonância Magnética , Doenças Neurodegenerativas , Histiocitose de Células de Langerhans/diagnóstico por imagem , Histiocitose de Células de Langerhans/terapia , Humanos , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/terapia , Guias de Prática Clínica como Assunto
12.
Pediatr Blood Cancer ; 65(4)2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29286565

RESUMO

Data on management of pediatric marginal zone lymphoma (MZL) are scarce. This retrospective study assessed characteristics and outcome in 66 patients who were <18 years old. Forty-four (67%) had an extranodal MZL (EMZL), 21 (32%) a nodal MZL (NMZL), and one patient a splenic MZL. Thirty-three patients (50%) received a variable combination of adjuvant chemotherapy/immunotherapy/radiotherapy, while the remainder, including 20 of 21 with NMZL, entered an active observation period. Overall survival was excellent (98 ± 2%), although 11 patients relapsed (17%; NMZL, n = 1; EMZL, n = 10), seven after any therapy and four after complete resection only. In conclusion, outcome of NZML, in particular, seems to be excellent after (in)complete resection and observation only.


Assuntos
Linfoma de Zona Marginal Tipo Células B/mortalidade , Linfoma de Zona Marginal Tipo Células B/fisiopatologia , Linfoma de Zona Marginal Tipo Células B/terapia , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Taxa de Sobrevida
13.
Pediatr Hematol Oncol ; 34(4): 187-198, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-29039989

RESUMO

Relapsed/refractory acute myeloid leukemia (AML) has an extremely poor prognosis. We describe 17 children and adolescents with relapsed/refractory AML who received clofarabine, cyclophosphamide, and etoposide. Seven patients (41%) responded: 4 with a complete response (CR); 1 with CR with incomplete platelet recovery; and 2 with a partial response. Additionally, 4 developed hypocellular marrow without evidence of leukemia; 5 patients had resistant disease; and 1 suffered early toxic death. After further therapy including transplantation, 4 patients (24%) are alive without evidence of disease at a median of 60 months. This anthracycline-free regimen may be studied for relapsed or refractory AML, but due to the high risk of marrow aplasia reduced doses of clofarabine and cyclophosphamide should be used.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Nucleotídeos de Adenina/administração & dosagem , Nucleotídeos de Adenina/efeitos adversos , Adolescente , Adulto , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Arabinonucleosídeos/administração & dosagem , Arabinonucleosídeos/efeitos adversos , Criança , Pré-Escolar , Clofarabina , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Masculino , Taxa de Sobrevida
14.
Blood ; 130(17): 1874-1875, 2017 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-29074592
15.
Ann Hematol ; 96(9): 1449-1456, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28597167

RESUMO

Clinical trials on childhood acute promyelocytic leukemia (APL) report early death (ED) rates of 3-8%, but predictors of thrombohemorrhagic (TH)-ED are not well understood. In a retrospective study, we aimed to determine the incidence and predictors of TH-ED in childhood APL. Data were analyzed from children and adolescents with t(15;17)-positive APL (n = 683) who started treatment with all-trans retinoic acid (ATRA) and chemotherapy in different international studies. Demographic data; initial white blood cell (WBC), peripheral blood (PB) blast, and platelet counts; hemoglobin value; coagulation parameters; morphologic variant (M3 or M3v); and induction details were analyzed. Early death was defined as death occurring within 30 days of presentation. The incidence of ED was 4.7% (32 of 683 patients). Predictors of TH-ED were identified by univariable and multivariable Cox proportional hazard regression analyses (n = 25). In univariable analysis, high WBC (>10 × 109/L) (P < 0.001) and high PB blast (>30 × 109/L) (P < 0.001), M3v (P < 0.01), and black ethnicity (P < 0.001) were independent predictors of TH-ED. In multivariable analysis, high WBC count (P < 0.01) and obesity (i.e., body mass index ≥95th percentile for age) (P = 0.03) were predictors of TH-ED. Initial high WBC counts and obesity are likely predictors of TH-ED in childhood APL. The efficacy of novel drugs for APL-associated coagulopathy or of frontline arsenic trioxide and ATRA combination regimens in reducing ED rates in childhood APL remains to be established.


Assuntos
Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 17/genética , Coagulação Intravascular Disseminada , Translocação Genética , Tretinoína , Adolescente , Adulto , Criança , Pré-Escolar , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/induzido quimicamente , Coagulação Intravascular Disseminada/genética , Coagulação Intravascular Disseminada/mortalidade , Feminino , Humanos , Lactente , Recém-Nascido , Leucemia Promielocítica Aguda/sangue , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/mortalidade , Contagem de Leucócitos , Masculino , Obesidade/sangue , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/mortalidade , Fatores de Risco , Tretinoína/administração & dosagem , Tretinoína/efeitos adversos
16.
Pediatr Blood Cancer ; 64(2): 302-305, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27577695

RESUMO

To study the prevalence of pediatric cancer patients who have underlying inherited bone marrow failure syndrome (IBMFS), we retrospectively reviewed the medical records of newly diagnosed pediatric cancer patients at The Hospital for Sick Children from June 2009 to May 2010, focusing on clinical, laboratory, and treatment-related findings which may indicate underlying IBMFS. We found five (1.8%) patients out of 276 who had two or more findings suggestive of IBMFS. We conclude that a small fraction of patients with cancer have clinical features that indicate investigations to rule out underlying IBMFSs. A prospective study is needed to determine their prevalence.


Assuntos
Doenças da Medula Óssea/diagnóstico , Neoplasias/complicações , Adolescente , Doenças da Medula Óssea/etiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Neoplasias/patologia , Prognóstico , Estudos Retrospectivos
17.
Hematology Am Soc Hematol Educ Program ; 2016(1): 386-389, 2016 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-27913505

RESUMO

A 14-year-old boy with no significant past medical history presents with headaches and vomiting and is found to have a 2 × 3-cm left parietal lobe mass. A stereotactic biopsy reveals diffuse large B-cell lymphoma (DLBCL). Cerebrospinal fluid cytology, as well as bone marrow biopsies are negative, and a whole-body positron emission tomography/computed tomography scan does not demonstrate other areas of disease. The primary medical team asks how you would treat this patient.


Assuntos
Neoplasias Encefálicas , Linfoma , Lobo Parietal/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adolescente , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Humanos , Linfoma/diagnóstico por imagem , Linfoma/terapia , Masculino
19.
Haematologica ; 101(12): 1581-1591, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27515251

RESUMO

Children and adolescents with pre-existing conditions such as DNA repair defects or other primary immunodeficiencies have an increased risk of non-Hodgkin lymphoma. However, large-scale data on patients with non-Hodgkin lymphoma and their entire spectrum of pre-existing conditions are scarce. A retrospective multinational study was conducted by means of questionnaires sent out to the national study groups or centers, by the two largest consortia in childhood non-Hodgkin lymphoma, the European Intergroup for Childhood non-Hodgkin Lymphoma, and the international Berlin-Frankfurt-Münster Study Group. The study identified 213 patients with non-Hodgkin lymphoma and a pre-existing condition. Four subcategories were established: a) cancer predisposition syndromes (n=124, 58%); b) primary immunodeficiencies not further specified (n=27, 13%); c) genetic diseases with no increased cancer risk (n=40, 19%); and d) non-classifiable conditions (n=22, 10%). Seventy-nine of 124 (64%) cancer predispositions were reported in groups with more than 20 patients: ataxia telangiectasia (n=32), Nijmegen breakage syndrome (n=26), constitutional mismatch repair deficiency (n=21). For the 151 patients with a known cancer risk, 5-year event-free survival and overall survival rates were 40%±4% and 51%±4%, respectively. Five-year cumulative incidences of progression/relapse and treatment-related death as a first event were 22%±4% and 24%±4%, respectively. Ten-year incidence of second malignancy was 24%±5% and 7-year overall survival of the 21 patients with a second malignancy was 41%±11%. Patients with non-Hodgkin lymphoma and pre-existing conditions have an inferior survival rate with a large proportion of therapy-related deaths compared to patients with non-Hodgkin lymphoma and no pre-existing conditions. They may require special vigilance when receiving standard or modified/reduced-intensity chemotherapy or when undergoing allogeneic stem cell transplantation.


Assuntos
Comorbidade , Suscetibilidade a Doenças , Linfoma não Hodgkin/epidemiologia , Vigilância em Saúde Pública , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/terapia , Masculino , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Recidiva , Resultado do Tratamento
20.
Pediatr Blood Cancer ; 63(11): 1915-21, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27392123

RESUMO

BACKGROUND: ZNF384 gene rearrangements with multiple partner genes are recurrent in acute leukemia and are most often associated with a precursor B cell immunophenotype. The overall incidence of this genetic category of leukemia is uncertain. PROCEDURE: Patients with ZNF384 gene rearrangements from a cohort of 240 precursor B cell acute lymphoblastic leukemia (ALL) pediatric patients over a 3.5-year time period were characterized with detailed cytogenetic, FISH, genomic, and clinical analyses. RESULTS: Seven of the 240 patients were identified to have ZNF384 gene rearrangements including partner genes TCF3 (four patients), EWSR1 (one patient), EP300 (one patient), and the novel gene partner ARID1B (one patient). The translocations were confirmed by FISH analysis and with RNA sequencing for the EP300 and ARID1B partner genes. Genomic microarray analysis showed an average of 2.7 copy number alterations in each case with no evidence of imbalance at the translocation breakpoints. Six of the patients with ZNF384 gene rearrangements had precursor B cell ALL with a CD10- immunophenotype and myeloid-associated antigens. One of the patients also had myeloperoxidase expression and was diagnosed as mixed phenotype B/myeloid acute leukemia. None of the patients have relapsed with event-free survival ranging from 6 years 2 months to 9 years 2 months. CONCLUSIONS: This study suggests that the frequency of ZNF384 gene rearrangement in pediatric precursor B cell ALL is approximately 3%. The ARID1B gene, commonly mutated in multiple types of cancer, was identified as an additional ZNF384 gene fusion partner.


Assuntos
Proteínas de Ligação a DNA/genética , Fusão Gênica , Rearranjo Gênico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Transativadores/genética , Fatores de Transcrição/genética , Translocação Genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Análise de Sequência de RNA
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