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1.
Haematologica ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33440924

RESUMO

Pediatric-onset Evans syndrome (pES) is defined by both immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) before the age of 18 years. There have been no comprehensive long-term studies of this rare disease, which can be associated to various immunopathological manifestations (IMs). We report outcomes of the 151 patients with pES and more than 5 years of follow-up from the nationwide French prospective OBS'CEREVANCE cohort. Median age at final follow-up was 18.5 (6.8-50.0) years and the median follow-up period was 11.3 (5.1-38.0) years. At 10 years, ITP and AIHA were in sustained complete remission in 54.5% and 78.4% of patients, respectively. The frequency and number of clinical and biological IMs increased with age: at 20 years old, 74% had at least one clinical cIM. A wide range of cIMs occurred, mainly lymphoproliferation, dermatological, gastrointestinal/hepatic and pneumological IMs. The number of cIMs was associated with a subsequent increase in the number of second-line treatments received (other than steroids and immunoglobulins; hazard ratio, 1.4; 95% confidence interval, 1.15-1.60; p = 0.0002, Cox proportional hazards method). Survival at 15 years after diagnosis was 84%. Death occurred at a median age of 18 (1.7-31.5) years, and the most frequent cause was infection. The number of second-line treatments and severe/recurrent infections were independently associated with mortality. In conclusion, longterm outcomes of pES showed remission of cytopenias but frequent IMs linked to high secondline treatment burden. Mortality was associated to drugs and/or underlying immunodeficiencies, and adolescents-young adults are a high-risk subgroup.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33454725

RESUMO

We included 255 patients from the L.E.A. French long-term follow-up cohort. All had received hematopoietic stem cell transplantation (HSCT) and/or testicular radiation for childhood acute leukemia and were older than 18 years at last L.E.A. evaluation. Total testosterone deficiency was defined as a <12 nmol/l level or by substitutive therapy, partial deficiency as normal testosterone with elevated luteinizing hormone (>10 UI/l). After myeloablative total body irradiation (n = 178), 55.6% had total deficiency, 15.7% partial deficiency, and 28.7% were normal. A 4-6 Gy testicular boost and a younger age at HSCT increased significantly the risk. After a Busulfan-containing myeloablative conditioning regimen (n = 53), 28.3% had total deficiency, 15.1% partial deficiency, 56.6% were normal (62.5% vs. 0% in patients without or with additional testicular radiation). A 24-Gy testicular radiation without HSCT induced total or partial deficiency in 71.4% and 28.6%, respectively (n = 21). Total testosterone deficiency increased the risk of metabolic syndrome: 25% vs. 12.1% in men with partial testosterone deficiency and 8.8% when Leydig cell function was normal (p = 0.031).

3.
Artigo em Inglês | MEDLINE | ID: mdl-32980546

RESUMO

Hematopoietic stem cell transplantation (HSCT) is a curative treatment for most hematologic diseases. To evaluate the level of donor engraftment, chimerism must be carefully monitored after HSCT. Short tandem repeats, quantitative PCR (qPCR), and, more recently, digital PCR (dPCR) are widely used to determine the proportions of donor and recipient cells after HSCT. The screening and quantification of chimerism have been evaluated by 2 new methods: a ready-to-use next-generation sequencing (NGS)-based method using the Devyser ChimerismNGS kit and an original combination of the Stilla crystal digital PCR (cdPCR) platform with 3-color multiplexing capacity using GenDX KMRtrack reagents. The genotyping of 4 HSCT pairs by cdPCR using 11 triplex mixes of the GenDX KMRtype kit was consistent at 98.8% with qPCR. Informative samples (n = 20) from 6 donor-recipient pairs and 1 external proficiency test demonstrated the reliability of the results (0.1% to 50%) for the 2 methods. The methods are also highly sensitive (0.1%) and accurate. The chimerism values of the 2 methods are correlated and concordant with those of the reference methods. In addition, the ADVYSER software (Devyser) is user-friendly and well adapted to chimerism monitoring. In conclusion, these 2 innovative methods are easy to perform and user-friendly in all molecular, hematology, and immunogenetic laboratories and allow the genotyping and monitoring of chimerism with high performance and sensitivity.

4.
Pediatr Blood Cancer ; 67(10): e28419, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32798263

RESUMO

INTRODUCTION: Our objectives were to assess the quality of life (QoL) of parents of childhood leukemia survivors compared with population norms and to identify the determinants of parents' long-term QoL. METHODS: Parents of minors who had survived childhood leukemia participating in the French LEA cohort (Leucémie de l'Enfant et de l'Adolescent-French Childhood Cancer Survivor Study for Leukemia) were asked to complete the French version of the WHOQOL-BREF. Results were compared with age- and sex-matched values from a French reference population. Parents' and survivors' characteristics likely to be associated with QoL, long after the child's leukemia diagnosis, were explored using multivariate analysis. RESULTS: We included 487 parents (mean age 42.9 ± 6.0 years, mean follow-up time from diagnosis 7.3 ± 3.3 years). Compared with the reference population, scores for physical health and social relationships for parents of childhood leukemia survivors were significantly lower (P < 0.001, effect size = 0.24 and P < 0.001, effect size = 0.29, respectively) contrary to scores for psychological health which were significantly higher (P < 0.001, effect size = 0.29). Even if health- and cancer-related characteristics were associated with parents' QoL in some dimensions, the only factor associated with each of the three dimensions (social relationships, physical health, and psychological) in the multivariate analysis was the parent's financial situation. CONCLUSIONS: Long after leukemia diagnosis, the parents reported lower scores in the physical health and social relationship domains. Despite the difficulties of actually influencing socioeconomic characteristics, it is important to consider the social situation of each family in the long-term care of survivors and their families.

5.
Bull Cancer ; 107(6): 629-632, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32387061

RESUMO

Since the emergence of the SARS-CoV-2 infection, many recommendations have been made. However, the very nature of acute lymphoblastic leukemias and their treatment in children and adolescents led the Leukemia Committee of the French Society for the fight against cancers and leukemias in children and adolescents (SFCE) to propose more specific recommendations, even if data for this population are still scarce. They may have to evolve according to the rapid evolution of knowledge on COVID-19.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/farmacocinética , Antivirais/uso terapêutico , Criança , Técnicas de Laboratório Clínico , Terapia Combinada , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Gerenciamento Clínico , Síndrome de Down/epidemiologia , Interações Medicamentosas , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/prevenção & controle , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Indução de Remissão , Risco , Medição de Risco , Terapia de Salvação , Avaliação de Sintomas
6.
Am J Hematol ; 95(7): 809-816, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32267023

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative for bone marrow failure in patients with Fanconi anemia (FA), but the presence of a malignant transformation is associated with a poor prognosis and the management of these patients is still challenging. We analyzed outcome of 74 FA patients with a diagnosis of myelodysplastic syndrome (n = 35), acute leukemia (n = 35) or with cytogenetic abnormalities (n = 4), who underwent allo-HSCT from 1999 to 2016 in EBMT network. Type of diagnosis, pre-HSCT cytoreductive therapies and related toxicities, disease status pre-HSCT, donor type, and conditioning regimen were considered as main variables potentially influencing outcome. The 5-year OS and EFS were 42% (30-53%) and 39% (27-51%), respectively. Patients transplanted in CR showed better OS compared with those transplanted in presence of an active malignant disease (OS:71%[48-95] vs 37% [24-50],P = .04), while none of the other variables considered had an impact. Twenty-two patients received pre-HSCT cytoreduction and 9/22 showed a grade 3-4 toxicity, without any lethal event or negative influence on survival after HSCT(OS:toxicity pre-HSCT 48% [20-75%] vs no-toxicity 51% [25-78%],P = .98). The cumulative incidence of day-100 grade II-IV a-GvHD and of 5-year c-GvHD were 38% (26-50%) and 40% (28-52%). Non-relapse-related mortality and incidence of relapse at 5-years were 40% (29-52%) and 21% (11-30%) respectively, without any significant impact of the tested variables. Causes of death were transplant-related events in most patients (34 out of the 42 deaths, 81%). This analysis confirms the poor outcome of transformed FA patients and identifies the importance of achieving CR pre-HSCT, suggesting that, in a newly diagnosed transformed FA patient, a cytoreductive approach pre-HSCT should be considered if a donor have been secured.


Assuntos
Anemia de Fanconi , Transplante de Células-Tronco Hematopoéticas , Leucemia , Síndromes Mielodisplásicas , Doença Aguda , Aloenxertos , Intervalo Livre de Doença , Anemia de Fanconi/complicações , Anemia de Fanconi/mortalidade , Anemia de Fanconi/terapia , Feminino , Seguimentos , Humanos , Leucemia/etiologia , Leucemia/mortalidade , Leucemia/terapia , Masculino , Síndromes Mielodisplásicas/etiologia , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Estudos Retrospectivos , Taxa de Sobrevida
7.
Bone Marrow Transplant ; 55(8): 1540-1551, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32203263

RESUMO

Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.

8.
Br J Haematol ; 189(5): 931-942, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32130726

RESUMO

Childhood chronic immune thrombocytopenic purpura (cITP) is a rare disease. In severe cases, there is no evidence for the optimal therapeutic strategy. Our aim was to describe the real-life management of non-selected children with cITP at diagnosis. Since 2004, patients less than 18 years old with cITP have been enrolled in the national prospective cohort, OBS'CEREVANCE. From 1990 to 2014, in 29 centres, 392 children were diagnosed with cITP. With a median follow-up of six years (2·0-25), 45% did not need second-line therapy, and 55% (n = 217) received one or more second lines, mainly splenectomy (n = 108), hydroxychloroquine (n = 61), rituximab (n = 61) or azathioprine (n = 40). The overall five-year further second-line treatment-free survival was 56% [95% CI 49·5-64.1]. The use of splenectomy significantly decreased over time. Hydroxychloroquine was administered to children with positive antinuclear antibodies, more frequently older and girls, and reached 55% efficacy. None of the patients died. Ten years after the initial diagnosis, 55% of the 56 followed children had achieved complete remission. Children with cITP do not need second-line treatments in 45% of cases. Basing the treatment decision on the pathophysiological pathways is challenging, as illustrated by ITP patients with positive antinuclear antibodies treated with hydroxychloroquine.

9.
Pediatr Blood Cancer ; 67(4): e28177, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31925926

RESUMO

BACKGROUND: Hepatitis-associated aplastic anemia (AA) is a rare syndrome combining acute hepatitis of variable severity and AA. Hepatitis may be severe enough to require urgent liver transplantation (LT). Herein, we describe clinical presentation and management of a cohort of pediatric patients diagnosed with AA after undergoing LT for nonviral hepatitis. METHODS: To describe this rare clinical situation, we performed a national survey and identified nine children treated for AA following LT during the last 10 years in France. RESULTS: All patients were treated first for hepatic failure with urgent LT. AA was diagnosed with a median delay of 34 days [21-200] from the diagnosis of hepatitis. Seven children were treated with antithymocyte globulin/cyclosporine, one with CSA alone and one received bone marrow transplantation. At the last visit (median follow-up: 4 years), outcomes were excellent: all patients were alive and in hematological remission (complete remission: 7; partial remission: 2). Immunosuppressive therapy was pursued in all patients due to the liver transplant. No unusual toxicities were reported. CONCLUSION: AA after LT is considered a therapeutic challenge. Nevertheless, hematological outcome is good using a standard immunosuppressive approach.


Assuntos
Anemia Aplástica , Hepatite , Imunossupressão/efeitos adversos , Transplante de Fígado , Adolescente , Anemia Aplástica/epidemiologia , Anemia Aplástica/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , França/epidemiologia , Hepatite/epidemiologia , Hepatite/etiologia , Hepatite/terapia , Humanos , Masculino
10.
Pediatr Infect Dis J ; 39(3): 258-259, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31876612

RESUMO

We are reporting a case of Bacillus Calmette-Guérin vaccine-disseminated infection in a 19-month-old HIV-negative girl diagnosed with severe combined immunodeficiency. While standard culture protocols failed to isolate and culture the Mycobacterium bovis Bacillus Calmette-Guérin strain, it was isolated from skin and mesenteric lymph node biopsies using the shell-vial assay, allowing whole-genome sequencing and in silico drug susceptibility testing.


Assuntos
Testes de Sensibilidade Microbiana/métodos , Mycobacterium bovis , Imunodeficiência Combinada Severa/complicações , Tuberculose/diagnóstico , Tuberculose/etiologia , Antituberculosos/uso terapêutico , Biópsia , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/métodos , Quimioterapia Combinada , Feminino , Humanos , Lactente , Linfonodos/microbiologia , Linfonodos/patologia , Mycobacterium bovis/efeitos dos fármacos , Mycobacterium bovis/genética , Mycobacterium bovis/imunologia , Imunodeficiência Combinada Severa/terapia , Úlcera Cutânea/etiologia , Úlcera Cutânea/patologia , Resultado do Tratamento , Tuberculose/tratamento farmacológico
11.
Biol Blood Marrow Transplant ; 25(12): 2438-2446, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31394275

RESUMO

Outcomes for adolescents and young adults (AYAs) with leukemia differ from other age groups and are still under-represented in clinical research. The aim of this study was to analyze outcomes of umbilical cord blood transplant (UCBT) in AYAs with acute leukemia reported to Eurocord/European Society for Blood and Marrow Transplantation. Patients (N = 504) had acute lymphoblastic (59%) or myeloid leukemia (41%), were aged 15 to 25 years, and received UCBT after myeloablative conditioning regimens between 2004 and 2016. The primary endpoint was 3-year overall survival (OS). Median follow-up was 3.9 years. Transplant was single in 58% and double UCBT in 42%. Three-year OS was 45% and leukemia free survival (LFS) was 41%. Cumulative incidence functions (CIFs) of nonrelapse mortality (NRM) and relapse were 31% and 28%, respectively. CIF of acute graft-versus-host disease (GVHD) grades II to IV at day 100 was 28%. Three-year CIF of chronic GVHD was 25%. In adjusted analysis, better disease status at UCBT (hazard ratio [HR], 2.74; P < .001) and more recent UCBT (HR, 1.43; P = .01) were associated with increased OS, and a similar effect of these factors was observed on LFS. Contrastingly, the use of antithymocyte globulin had a negative effect in LFS. The risk of acute GVHD grades II to IV increased with the use of double UCBT (HR, 1.65; P  = .02) and decreased with more recent transplant period (HR, .65; P = .02) and antithymocyte globulin use (HR, .55; P  = .01). Outcomes of AYA UCBT improved in more recent years, becoming comparable with pediatric results. Demonstrating the feasibility of UCBT in AYAs facilitates stem cell source selection and provides the basis for future prospective studies.


Assuntos
Soro Antilinfocitário/administração & dosagem , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sistema de Registros , Doadores não Relacionados , Doença Aguda , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Incidência , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Retrospectivos , Taxa de Sobrevida
12.
Biol Blood Marrow Transplant ; 25(9): 1786-1791, 2019 09.
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.


Assuntos
Bussulfano/análogos & derivados , Gônadas/metabolismo , Transplante de Células-Tronco Hematopoéticas , Puberdade Precoce , Adolescente , Adulto , Aloenxertos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Criança , Pré-Escolar , Feminino , Gônadas/patologia , Humanos , Masculino , Puberdade Precoce/induzido quimicamente , Puberdade Precoce/metabolismo , Puberdade Precoce/patologia , Estudos Retrospectivos
14.
Endocr Connect ; 8(4): 349-359, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30844749

RESUMO

Background/objective: The number of long-term survivors of childhood acute leukemia (AL) is substantially growing. These patients are at high risk for metabolic syndrome (MS), especially those who received total body irradiation (TBI). The consequences of children's irradiation on adipose tissue (AT) development in adulthood are currently unknown. The objective of this study is to assess the impact of TBI on AT of childhood AL survivors. Design: We compared the morphological and functional characteristics of AT among survivors of childhood AL who developed MS and received (n = 12) or not received (n = 12) TBI. Subjects/methods: Body fat distribution and ectopic fat stores (abdominal visceral and liver fat) were evaluated by DEXA, MRI and 1H-spectroscopy. Functional characteristics of subcutaneous AT were investigated by studying gene expression and pre-adipocyte differentiation in culture. Results: Patients who have received TBI exhibited a lower BMI (minus 5 kg/m2) and a lower waist circumference (minus 14 cm), especially irradiated women. Despite the lower quantity of intra-abdominal AT, irradiated patient displayed a nearly two-fold greater content of liver fat when compared to non-irradiated patient (17 vs 9%, P = 0.008). These lipodystrophic-like features are supplemented by molecular abnormalities in subcutaneous AT of irradiated patients: decrease of gene expression of SREBP1 (minus 39%, P = 0.01) and CIDEA (minus 36%, P = 0.004) and a clear alteration of pre-adipocyte differentiation. Conclusions: These results strongly support the direct effect of irradiation on AT, especially in women, leading to specific nonalcoholic fatty liver disease, despite lower BMI. A long-term appropriate follow-up is necessary for these patients.

15.
Cancer ; 125(13): 2300-2308, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30913309

RESUMO

BACKGROUND: Efforts to improve the quality of end-of-life (EOL) care depend on better knowledge of the care that children, adolescents, and young adults with cancer receive, including high-intensity EOL (HI-EOL) care. The objective was to assess the rates of HI-EOL care in this population and to determine patient- and hospital-related predictors of HI-EOL from the French national hospital database. METHODS: This was a population-based, retrospective study of a cohort of patients aged 0 to 25 years at the time of death who died at hospital as a result of cancer in France between 2014 and 2016. The primary outcome was HI-EOL care, defined as the occurrence of ≥1 chemotherapy session <14 days from death, receiving care in an intensive care unit ≥1 time, >1 emergency room admission, and >1 hospitalization in an acute care unit in the last 30 days of life. RESULTS: The study included 1899 individuals from 345 hospitals; 61.4% experienced HI-EOL care. HI-EOL was increased with social disadvantage (adjusted odds ratio [AOR], 1.30; 95% confidence interval [CI], 1.03-1.65; P = .028), hematological malignancies (AOR, 2.09; 95% CI, 1.57-2.77; P < .001), complex chronic conditions (AOR, 1.60; 95% CI, 1.23-2.09; P = .001) and care delivered in a specialty center (AOR, 1.70; 95% CI, 1.22-2.36; P = .001). HI-EOL was reduced in cases of palliative care (AOR, 0.31; 95% CI, 0.24-0.41; P < .001). CONCLUSION: A majority of children, adolescents, and young adults experience HI-EOL care. Several features (eg, social disadvantage, cancer diagnosis, complex chronic conditions, and specialty center care) were associated with HI-EOL care. These findings should now be discussed with patients, families, and professionals to define the optimal EOL.


Assuntos
Bases de Dados Factuais , Neoplasias/terapia , Cuidados Paliativos/métodos , Cuidados Paliativos/estatística & dados numéricos , Assistência Terminal/métodos , Assistência Terminal/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , França/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias/epidemiologia , Neoplasias/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
16.
Cytometry B Clin Cytom ; 96(2): 128-133, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30734503

RESUMO

BACKGROUND: In children with acute lymphoblastic leukemia (ALL) low levels of minimal residual disease (MRD) after induction, essentially assessed in the bone marrow, have been shown to be of good prognosis. However, only few studies have tested the peripheral blood for MRD. METHODS: Here, we report the impact on survival of peripheral blood (PB) MRD assessment by multiparameter flow cytometry (MFC) at early time points of treatment in 125 B-ALL children, compared to Day 35 molecular bone marrow (BM) MRD. Patients were sampled for MFC one week postdiagnosis after a pre-phase of corticotherapy (Day 8), then after one week of chemotherapy (Day 15). The study enrolled 67 boys and 58 girls with a median follow-up of 52 months. Over the duration of the study, 20 patients relapsed and eight died. MFC was performed based on the leukemia-associated immunophenotype at diagnosis, using panels of 10 antibodies. RESULTS: Although, PB MFC-MRD had no prognostic impact at Day 8, Day 15 MRD negativity was associated with a significantly better 4 years DFS (91.6 ± 3% vs. 67.6 ± 9% P = 0.0013). Furthermore, while MFC and molecular data were concordant in most cases, patients with detectable PB MRD on Day 15, yet negative in BM on Day 35 had a significantly lower DFS (P < 0.0001). CONCLUSION: This study demonstrates that the less invasive procedure of MFC-MRD assessment in PB can be informative for childhood ALL patients at the early point of Day 15 of the treatment schedule. © 2019 International Clinical Cytometry Society.


Assuntos
Citometria de Fluxo , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Neoplasia Residual/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras B/sangue
17.
J Clin Immunol ; 39(2): 171-181, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30671780

RESUMO

PURPOSE: Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) are associated in the definition of Evans syndrome (ES). The occurrence of neurological involvement in this population is poorly described and suggests an underlying primary immunodeficiency (PID). We aimed to describe the clinical manifestations, evolution, and PID profiles of these patients. METHODS: OBS'CEREVANCE is a French, nationwide prospective cohort that includes children with chronic ITP, AIHA, and ES. Patients with a neurological involvement were described. Centralized radiological and pathological reviews and genetic analyses were performed. RESULTS: On October 2016, eight patients (7/181 ES, 1/371 AIHA, and 0/615 ITP) were identified, all male, with a median age (range) at cytopenia onset of 11.5 years (1.6-15.8). Neurological symptoms appeared with a median delay of 6 years (2.5-18) after cytopenia and were polymorphic: seizures (n = 4), cranial nerve palsy (n = 2), Brown-Sequard syndrome (n = 2), intracranial pressure (n = 2), vertigo (n = 1), and/or sensory neuropathy (n = 1). Magnetic resonance imaging (MRI) showed inflammatory lesions, confirmed by pathology for five patients with macrophagic or lymphoplasmocytic infiltrates. All patients had other relevant immunopathological manifestations: pulmonary nodules (n = 6), lymphoproliferation (n = 4), abnormal immunophenotype (n = 8), and hypogammaglobulinemia (n = 7). Treatment consisted of steroids that improved symptomatology and MRI. Five patients relapsed and three had an asymptomatic radiological progression. A PID was identified in 3/8 patients: 22q11.2 microdeletion (n = 1) and CTLA deficiency (n = 2). CONCLUSION: Neurological involvement is a rare and severe late event in the course of childhood ES, which can reveal an underlying PID. Imaging and pathology examination highlight a causative immune dysregulation that may guide targeted therapeutic strategies.


Assuntos
Anemia Hemolítica Autoimune , Doenças do Sistema Nervoso , Doenças da Imunodeficiência Primária , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Adolescente , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/tratamento farmacológico , Criança , Pré-Escolar , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Masculino , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Esteroides/uso terapêutico , Trombocitopenia/diagnóstico , Trombocitopenia/tratamento farmacológico
18.
Front Oncol ; 9: 1374, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31921638

RESUMO

Background: B-cell acute lymphoblastic leukemia associated with t(5;14)(q31;q32); IGH-IL3 is an exceptional cause of eosinophilia. The IGH enhancer on 14q32 is juxtaposed to the IL3 gene on 5q31, leading to interleukin-3 overproduction and release of mature eosinophils in the blood. Clinical, biological and outcome data are extremely scarce in the literature. Except for eosinophilia, no relevant common feature has been highlighted in these patients. However, it has been classified as a distinct entity in the World Health Organization classification. Cases Presentation: Eight patients with t(5;14)(q31;q32) treated by French or Austrian protocols were retrospectively enrolled. Array comparative genomic hybridization, multiplex ligation-dependent probe amplification or genomic PCR search for IKZF1 deletion were performed in 7. Sixteen patients found through an exhaustive search in the literature were also analyzed. For those 24 patients, median age at diagnosis is 14.3 years with a male predominance (male to female ratio = 5). Eosinophilia-related symptoms are common (neurologic in 26%, thromboembolic in 26% or pulmonary in 50%). Median white blood cells count is high (72 × 109/L) and linked to eosinophilia (median: 32 × 109/L). Peripheral blasts are present at a low level or absent (median: 0 × 109/L; range: 0-37 × 109/L). Bone marrow morphology is marked by a low blast infiltration (median: 42%). We found an IKZF1 deletion in 5 out of 7 analyzable patients Outcome data are available for 14 patients (median follow-up: 28 months): 8 died and 6 are alive in complete remission. Some of these features are concordant with those seen in patients with other IGH-rearranged B-cell acute lymphoblastic leukemias: young age at onset, male sex, low blast count, high incidence of IKZF1 deletion and intermediate prognosis. Conclusion: Based on shared epidemiological and biological features, B-cell acute lymphoblastic leukemia with t(5;14)(q31;q32) is a peculiar subset of IGH-rearranged B-cell acute lymphoblastic leukemia with an intermediate prognosis and particular clinical features related to eosinophilia.

19.
Leukemia ; 33(2): 348-357, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30089916

RESUMO

Despite constant progress in prognostic risk stratification, children with acute myeloid leukemia (AML) still relapse. Treatment failure and subsequent relapse have been attributed to acute myeloid leukemia-initiating cells (LSC), which harbor stem cell properties and are inherently chemoresistant. Although pediatric and adult AML represent two genetically very distinct diseases, we reasoned that common LSC gene expression programs are shared and consequently, the highly prognostic LSC17 signature score recently developed in adults may also be of clinical interest in childhood AML. Here, we demonstrated prognostic relevance of the LSC17 score in pediatric non-core-binding factor AML using Nanostring technology (ELAM02) and RNA-seq data from the NCI (TARGET-AML). AML were stratified by LSC17 quartile groups (lowest 25%, intermediate 50% and highest 25%) and children with low LSC17 score had significantly better event-free survival (EFS: HR = 3.35 (95%CI = 1.64-6.82), P < 0.001) and overall survival (OS: HR = 3.51 (95%CI = 1.38-8.92), P = 0.008) compared with patients with high LSC17 scores. More importantly, the high LSC17 score was an independent negative EFS and OS prognosticator determined by multivariate Cox model analysis (EFS: HR = 3.42 (95% CI = 1.63-7.16), P = 0.001; OS HR = 3.02 (95%CI = 1.16-7.85), P = 0.026). In conclusion, we have demonstrated the broad applicability of the LSC17 score in the clinical management of AML by extending its prognostic relevance to pediatric AML.


Assuntos
Biomarcadores Tumorais/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Células-Tronco Neoplásicas/patologia , Transcriptoma , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/classificação , Masculino , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Taxa de Sobrevida
20.
Br J Haematol ; 184(3): 397-404, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30460979

RESUMO

Allogeneic haematopoietic stem cell transplantation is still the only available curative option for Familial Haemophagocytic Lymphohistiocytosis (FHLH). Most studies report outcomes after bone marrow or peripheral blood stem cell transplantation. We analysed the outcomes of 118 children with FHLH undergoing single-unit umbilical cord blood transplantation performed from 1996 to 2014. Myeloablative conditioning regimen was given to 90% of the patients, and was mostly busulfan-based (n = 81, 76%), including anti-thymocyte globulin or alemtuzumab (n = 102, 86%). The cumulative incidence of Day 60 neutrophil engraftment was 85%; and that of non-relapse mortality and acute graft-versus-host disease (GvHD) was 21% and 33% at 100 days, respectively. The 6-year cumulative incidence of chronic GvHD was 17% and the 6-year probability of overall survival was 55%. In multivariate analysis, children receiving a graft with a total nucleated cell dose greater than 9·9 × 107 /kg had a better overall survival (hazard ratio [HR]: 0·49, 95% CI: 0·27-0·88, P = 0·02). Degree of human leucocyte antigen (HLA) matching was associated with improved disease-free survival (5/6 vs. 6/6 HR: 2·11, 95% confidence interval [CI]: 1·01-4·4, P = 0·05 and ≤4/6 vs. 6/6, HR: 2·82, CI: 1·27-6·23, P = 0·01). Umbilical cord blood transplantation with a high cell dose and good HLA match is a suitable alternative option to haematopoietic stem cell transplantation in children with FHLH who lack a HLA-matched donor.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Linfo-Histiocitose Hemofagocítica , Condicionamento Pré-Transplante , Doadores não Relacionados , Adolescente , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Recém-Nascido , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
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