RESUMO
PURPOSE: To investigate the role of parental smoking during pre-conception and pregnancy, maternal beverage consumption (alcohol, coffee and tea) during pregnancy and their possible interactions, in the etiology of childhood acute leukemia (CL). METHODS: The ESTELLE study included 747 cases of CL [636 cases of acute lymphoblastic leukemia (ALL) and 100 cases of acute myeloblastic leukemia (AML)] diagnosed in France in 2010-2011 and 1,421 population controls frequency-matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to the mothers. The odds ratios (OR) and their 95 % confidence intervals were estimated using unconditional logistic regression models adjusted for potential confounders. RESULTS: AML, but not ALL, was non-significantly associated with alcohol drinking during pregnancy [OR = 1.3 (0.8-2.0)] with a significant positive dose-response trend (p-trend = 0.02). Pre-conception paternal smoking was significantly associated with ALL [OR = 1.2 (1.1-1.5)] and AML [OR = 1.5 (1.0-2.3)]. CL was not associated with maternal smoking [OR = 1.0 (0.8-1.2)], or maternal coffee [OR = 0.9 (0.8-1.1)] or tea drinking [OR = 0.9 (0.8-1.1)] during pregnancy. However, a high consumption of coffee (>2 cups/day) was significantly associated with ALL [OR = 1.3 (1.0-1.8)]. CONCLUSIONS: The findings constitute additional evidence that maternal alcohol drinking during pregnancy may be involved in AML, and that paternal smoking before pregnancy may be a risk factor for CL. The role of maternal coffee drinking in CL remains unclear and should be investigated further in consortium analyses and in large birth cohort studies with exposure assessment more contemporaneous with the exposure, before the occurrence of the disease.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Leucemia Mieloide Aguda/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Efeitos Tardios da Exposição Pré-Natal , Fumar/epidemiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Café , Feminino , França/epidemiologia , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Razão de Chances , Pais , Gravidez , Fatores de Risco , Inquéritos e Questionários , CháRESUMO
BACKGROUND: The association between acute childhood leukaemia and residing next to petrol stations and automotive repair garages was analysed in a national registry-based case-control study carried out in France in 2003-2004. METHODS: Population controls were frequency matched with cases on age and gender. Data were collected by standardised telephone interview with the mothers. The latter were asked to report the proximity of their homes to petrol stations, automotive repair garages and other businesses from the conception of the index child to the diagnosis (for cases) or interview (for controls). Odds ratios were estimated using unconditional regression models adjusted for age, gender, number of children under 15 years of age in the household, degree of urbanisation and type of housing. RESULTS: 765 cases of acute leukaemia and 1681 controls were included. Acute leukaemia was significantly associated with residence next to petrol stations or automotive repair garages (OR 1.6, 95% CI 1.2 to 2.2) and next to a petrol station (OR 1.9, 95% CI 1.2 to 3.0). The OR showed no tendency to increase with duration of exposure. The results were not modified by adjustment for potential confounding factors including urban/rural status and type of housing. CONCLUSIONS: The results support the findings of our previous study and suggest that living next to a petrol station may be associated with acute childhood leukaemia. The results also suggest that the role of low-level exposure to benzene in acute childhood leukaemia deserves further evaluation.
Assuntos
Exposição Ambiental/efeitos adversos , Gasolina/efeitos adversos , Leucemia/epidemiologia , Doença Aguda , Adolescente , Distribuição por Idade , Poluentes Atmosféricos/efeitos adversos , Benzeno/efeitos adversos , Carcinógenos Ambientais/efeitos adversos , Estudos de Casos e Controles , Criança , Pré-Escolar , Escolaridade , Exposição Ambiental/análise , Monitoramento Ambiental/métodos , Monitoramento Epidemiológico , Feminino , França/epidemiologia , Humanos , Lactente , Recém-Nascido , Leucemia/etiologia , Masculino , Características de Residência , Distribuição por Sexo , Classe SocialRESUMO
The clinical and biological characteristics of children under 2 years (infants) with acute myeloid leukemia (AML) are different from those of older children. We aimed to describe the specific characteristics of this population and the potential factors that influence the prognosis. We analyzed data concerning 438 children with newly-diagnosed AML treated in the ELAM02 protocol between March 2005 and December 2011, of which 103 were under 2 years old at diagnosis. The evaluation criteria were overall survival (OS) and event-free survival (EFS) of infants vs older children. The clinical and biological features were secondary criteria. Infants presented more frequent extra-medullary presentation than older children. They had a significantly higher proportion of skin lesions and central nervous system involvement (15% vs 3%, pâ<â0.0001 and 26% vs 12%, pâ=â0.0005, respectively). The global incidence of KMT2A rearrangements was nearly 55% for infants vs 11% for older children (pâ<â0.0001). Median 5-year OS was 70.4% for infants vs 71.4% for older children (pâ=â0.83). Five-year EFS was 67% for infants vs 58% for older children (pâ=â0.27). Infants with AML represent a cohort of patients with specific clinical and biological features. These remarkable differences had no significant impact on their outcome in the ELAM02 protocol.
RESUMO
There is no consensus on the type of nutritional support to introduce in children undergoing allogeneic stem cell transplantation (allo-SCT) after myeloablative conditioning (MAC). This retrospective, multicenter, observational study compared the early administration of enteral nutrition (EN group, n = 97) versus parenteral nutrition (PN group, n = 97) in such patients with matching for important covariates. The primary endpoint was the study of day 100 overall mortality. The early outcome at day 100 was better in EN group regarding mortality rate (1% vs. 13%; p = 0.0127), non relapse mortality (1% vs. 7%; p = 0.066), acute GVHD grades II-IV (37% vs. 54%; p = 0.0127), III-IV (18% vs. 34%; p = 0.0333) and its gut localization (16% vs. 32%; p = 0.0136). Platelet engraftment was better in EN group than in PN group for the threshold of 20 G/L (97% vs. 80% p < 0.0001) and 50 G/L (92% vs. 78%, p < 0.0001). The length of stay was shorter in EN group (28 vs. 52 days, p < 0.0001). There were no differences between the two groups regarding the polynuclear neutrophil engraftment, infection rate or mucositis occurrence. These results suggest that, in children undergoing MAC allo-SCT, PN should be reserved to the only cases when up-front EN is insufficient or impossible to perform.
Assuntos
Nutrição Enteral , Transplante de Células-Tronco Hematopoéticas , Nutrição Parenteral , Transplante Homólogo , Adolescente , Peso Corporal , Criança , Pré-Escolar , Nutrição Enteral/efeitos adversos , Nutrição Enteral/estatística & dados numéricos , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Neoplasias Hematológicas/cirurgia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Masculino , Nutrição Parenteral/efeitos adversos , Nutrição Parenteral/estatística & dados numéricos , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante Homólogo/efeitos adversos , Transplante Homólogo/mortalidade , Transplante Homólogo/estatística & dados numéricos , Resultado do TratamentoRESUMO
BACKGROUND: Previous studies on the putative role of allergy in the aetiology of childhood leukaemia have reported contradictory results. The present study aimed to analyse the relation between a medical history of asthma or eczema and childhood acute lymphoid leukaemia (ALL) in light of potential candidate gene-environment interactions. METHODS: Analyses were based on a subset of 434 cases of ALL and 442 controls successfully genotyped and of European ancestry children enrolled in a French population-based case-control study conducted in 2003-2004. Information about medical history was obtained during a standardized interview with the mothers. Candidate polymorphisms in genes of the Th2 cytokines IL4, IL10, IL13 and IL4-receptor, were genotyped or imputed. RESULTS: None of the variant alleles were directly associated with childhood acute lymphoid leukaemia. A medical history of asthma or eczema was reported more often in the control group (ORâ¯=â¯0.7 [0.5-1.0]). This association was mostly seen in the group of children not carrying the IL13-rs20541 variant allele (Interaction Odds Ratio IOR 1.9, p-interactionâ¯=â¯0.07) and in those carrying the IL10 triple variant haplotype (IOR 0.5, p-interactionâ¯=â¯0.04). No interaction was observed with the candidate polymorphisms in IL4 and IL4R. CONCLUSION: This study provides a new insight into the relationship between allergic symptoms and childhood acute lymphoid leukaemia, by suggesting this inverse association could be limited to children carrying certain genetic polymorphisms. If confirmed, these results could help better understand the biological mechanisms involved in the development of childhood acute lymphoid leukaemia.
Assuntos
Asma/genética , Eczema/genética , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Células Th2/metabolismo , Alelos , Asma/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Eczema/epidemiologia , Feminino , França/epidemiologia , Genótipo , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologiaRESUMO
A multicentric phase 2 study was conducted to determine the efficiency and the tolerance of imatinib mesylate in children with chronic myelogenous leukemia (CML) in advanced phase of the disease, in relapse after stem cell transplantation, or in case of failure to an interferon alpha-based regimen. In all, 30 children from eight European countries were enrolled. In 18 children assessable for hematologic response, imatinib mesylate induced complete hematologic response in eight (80%) of the 10 patients included in chronic phase and in six (75%) of eight enrolled in advanced phase of the disease with acceptable toxicity. In 27 patients assessable for cytogenetic response, imatinib mesylate induced disappearance of Philadelphia chromosome-positive bone marrow cells in 12 (60%) of 20 children included in chronic phase and in two (29%) of seven included in advanced phase. A reduction of the bcr-abl/abl ratio to less than 10(-4) was achieved in 11 (50%) of the children included in chronic phase. Estimated 12-month overall survival rate was 95% (95% CI, 87-100%) for the patients included in chronic phase and 75% (95%CI, 45-100%) for those enrolled in advanced phase. Imatinib mesylate is well tolerated and molecular remission can be achieved in children with CML.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Transplante de Células-Tronco , Adolescente , Benzamidas , Criança , Pré-Escolar , Doença Crônica , Esquema de Medicação , Europa (Continente) , Feminino , Seguimentos , Humanos , Mesilato de Imatinib , Lactente , Masculino , Recidiva , Indução de Remissão , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Allogeneic hematopoietic stem cell transplantation (SCT) contributes to improved outcome in childhood acute leukemia (AL). However, therapeutic options are poorly defined in the case of post-transplantation relapse. We aimed to compare treatment strategies in 334 consecutive children with acute leukemia relapse or progression after SCT in a recent 10-year period. Data could be analyzed in 288 patients (157 ALL, 123 AML and 8 biphenotypic AL) with a median age of 8.16 years at transplantation. The median delay from first SCT to relapse or progression was 182 days. The treatment consisted of chemotherapy alone (n=108), chemotherapy followed by second SCT (n=70), supportive/palliative care (n=67), combination of chemotherapy and donor lymphocyte infusion (DLI; n=30), or isolated reinfusion of donor lymphocytes (DLI; n=13). The median OS duration after relapse was 164 days and differed according to therapy: DLI after chemotherapy=385 days, second allograft=391 days, chemotherapy=174 days, DLI alone=140 days, palliative care=43 days. A second SCT or a combination of chemotherapy and DLI yielded similar outcome (hazard ratio (HR)=0.85, P=0.53) unlike chemotherapy alone (HR=1.43 P=0.04), palliative care (HR=4.24, P<0.0001) or isolated DLI (HR=1,94, P<0.04). Despite limitations in this retrospective setting, strategies including immunointervention appear superior to other approaches, mostly in AML.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia/terapia , Doença Aguda , Criança , Progressão da Doença , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia/mortalidade , Leucemia Aguda Bifenotípica/mortalidade , Leucemia Aguda Bifenotípica/terapia , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Transfusão de Linfócitos , Cuidados Paliativos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Falha de Tratamento , Resultado do TratamentoRESUMO
We analyzed the impact of cytogenetics on 193 children enrolled in two successive French trials (LAME89/91 and ELAM02), who received hematopoietic stem cell transplantation during CR1. Detailed karyotype was available for 66/74 (89%) in LAME89/91 and 118/119 (99%) in ELAM02. Several karyotype and transplant characteristics differed according to therapeutic protocol: unfavorable karyotypes were more frequent in ELAM02 (36% vs 18%), pretransplant chemotherapy included high-dose cytarabine in ELAM02 and not in LAME89/91, IV replaced oral busulfan in the conditioning regimen, methotrexate was removed from post-transplant immunosuppression, and matched unrelated donor and cord blood transplantation were introduced. Five-year overall survival (OS) was 78.2% in LAME89 and 81.4% in ELAM02. OS was significantly lower for the unfavorable cytogenetic risk group in LAME89/91 when compared with intermediate and favorable groups (50% vs 90.6 and 86.4%, P=0.001). This difference was no longer apparent in ELAM02 (80.9% vs 71.3% and 5/5, respectively). Survival improvement for children with unfavorable karyotype was statistically significant (P=0.026) and was due to decrease in relapse risk. Five-year transplantation-related mortality was 6.75% in LAME89/91. In ELAM02, it was 3.2% for patients with a sibling donor and 10.9% with an unrelated donor or cord blood. We conclude that the outcome of children with unfavorable karyotype transplanted in CR1 has improved.
Assuntos
Citogenética , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Criança , Feminino , França , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Cariotipagem , Leucemia Mieloide Aguda/mortalidade , Masculino , Indução de Remissão , Análise de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
OBJECTIVES: To investigate the relation between childhood acute leukaemia and household exposure to pesticides. METHODS: The study included 280 incident cases of acute leukaemia and 288 controls frequency matched on gender, age, hospital, and ethnic origin. The data were obtained from standardised face to face interviews of the mothers with detailed questions on parental occupational history, home and garden insecticide use, and insecticidal treatment of pediculosis. Odds ratios were estimated using unconditional regression models including the stratification variables parental socioeconomic status and housing characteristics. RESULTS: Acute leukaemia was observed to be significantly associated with maternal home insecticide use during pregnancy (OR = 1.8, 95% CI 1.2 to 2.8) and during childhood (OR = 1.7, 95% CI 1.1 to 2.4), with garden insecticide use (OR = 2.4, 95% CI 1.3 to 4.3), and fungicide use (OR = 2.5, 95% CI 1.0 to 6.2) during childhood. Insecticidal shampoo treatment of pediculosis was also associated with childhood acute leukaemia (OR = 1.9, 95% CI 1.2 to 3.3). CONCLUSION: The results reported herein support the hypothesis that various types of insecticide exposure may be a risk factor for childhood acute leukaemia. The observed association with insecticidal shampoo treatment of pediculosis, which has never been investigated before, requires further study.
Assuntos
Leucemia/induzido quimicamente , Praguicidas/toxicidade , Doença Aguda , Adolescente , Criança , Pré-Escolar , Exposição Ambiental/efeitos adversos , Métodos Epidemiológicos , Feminino , Humanos , Lactente , Recém-Nascido , Inseticidas/toxicidade , Infestações por Piolhos/tratamento farmacológico , Masculino , Exposição Materna/efeitos adversos , Exposição Paterna/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Dermatoses do Couro Cabeludo/tratamento farmacológicoRESUMO
We report a case of neuroblastoma diagnosed after adrenal haemorrhage following a minor trauma in a thirteen-month-old boy. Minor trauma is not commonly described as a cause of AH in the literature. Therefore when no accepted cause for AH can be found in a young child below the age of 5 years, it is important to look for a neuroblastoma and discuss the necessity of surgical exploration.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Hemorragia/etiologia , Neuroblastoma/diagnóstico , Acidentes por Quedas , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/cirurgia , Glândulas Suprarrenais/irrigação sanguínea , Evolução Fatal , Humanos , Lactente , Masculino , Neuroblastoma/complicações , Neuroblastoma/genética , Neuroblastoma/cirurgia , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To determine whether granulocyte colony-stimulating factor (G-CSF; lenograstim) decreases the incidence of febrile neutropenia after induction courses in treatment of childhood non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients were randomized to receive (G-CSF+) or not receive (G-CSF-) prophylactic G-CSF, 5 microg/kg/d, from day 7 until an absolute neutrophil count > or = 500/microL was sustained over 48 hours, after two consecutive induction courses of cyclophosphamide 1.5 or 3 g/m(2), vincristine 2 mg/m(2), prednisone 60 mg/m(2)/d x 5, doxorubicin 60 mg/m(2), high-dose methotrexate 3 or 8 g/m(2), and intrathecal injections (COPAD[M]) on protocols LMB89, LMT89, and HM91 of the French Society of Pediatric Oncology. RESULTS: One hundred forty-eight patients were assessable, 75 G-CSF+ and 73 G-CSF-. Although duration of neutropenia less than 500/microL was 3 days shorter in G-CSF+ patients (P = 10(-4)), incidence of febrile neutropenia (89% v. 93% in the first course, 88% v. 88% in the second course), durations of hospitalization and antimicrobial therapy, percentages of infections, mucositis, and transfusions were not significantly different. Although the percentage of G-CSF+ patients commencing the following course on day 21 was significantly higher (84% v 68% after the first and 57% v. 38% after the second course; P <.05), the median delay between the two courses was only 1 day less in G-CSF+ patients (median delay after first COPAD(M), 19 v. 20 days, P =.01; after second, 21 v. 22 days, P = not significant). Remission and survival rates were similar in both arms. CONCLUSION: This study demonstrates that G-CSF did not decrease treatment-related morbidity, nor increase the dose-intensity in children undergoing COPAD(M) induction chemotherapy for NHL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/farmacologia , Linfoma não Hodgkin/tratamento farmacológico , Neutropenia/prevenção & controle , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transfusão de Sangue , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Hospitalização , Humanos , Infecções , Masculino , Metotrexato/administração & dosagem , Morbidade , Prednisona/administração & dosagem , Estomatite/induzido quimicamente , Vincristina/administração & dosagemRESUMO
PURPOSE: To correlate the presence of p53 mutations and initial characteristics, response to chemotherapy, and survival in newly diagnosed Burkitt's lymphoma (BL) and Burkitt's acute lymphoblastic leukemia (L3 ALL). PATIENTS AND METHODS: Forty-eight patients with newly diagnosed BL or L3 ALL, most of whom were treated with very intensive regimens, including early CNS disease treatment, were studied. Detection of p53 mutations was made by single-strand conformation polymorphism (SSCP) analysis of exons 5 to 8 of the gene, and mutations were determined by direct sequencing of exons with abnormal SSCP findings. Comparison of outcome between mutated and nonmutated cases was made in all patients and also after excluding five patients who received therapeutic regimens considered as suboptimal and one patient who died of AIDS while in complete remission (CR), as those six patients had no p53 mutations. RESULTS: A point mutation was found in nine patients (19%), and consisted of a missense mutation in seven and a chain-terminating mutation in two. SSCP, sequence, and cytogenetic analysis strongly suggested that eight of nine patients with mutations had retained the normal p53 allele, which had been lost in the remaining patient. These findings were confirmed by fluorescence-in-situ hybridization (FISH) with a p53-specific probe in two patients, including the one who had lost the normal p53 allele. Unexpectedly, mutations were significantly less frequent in patients with disseminated disease, ie, L3 ALL or stage IV BL (four of 35, 11%), than in more localized forms, ie, BL stage I, II, or III (five of 13, 38%) (P = .03). CR rates were similar in mutated (78%) and nonmutated cases (78%). The actuarial disease-free interval (DFI) after 12 months and actuarial survival rates after 24 months were 49% and 66%, respectively, in patients with mutations, and 73% and 48%, respectively, those without mutations. The differences were not significant. CONCLUSION: Our findings suggest that, contrary to what is seen in most other neoplasias, p53 mutations in newly diagnosed BL and L3 ALL are not associated with extensive tumor mass or poor response to intensive therapeutic regimens. It is hypothesized that this difference with most tumors could be due to the fact that p53 mutations in BL and L3 ALL are generally associated with persistence of a normal residual p53 allele, contrary to what is observed in the majority of tumors.
Assuntos
Linfoma de Burkitt/genética , Genes p53/genética , Mutação Puntual , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Análise Atuarial , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sequência de Bases , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/mortalidade , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Taxa de SobrevidaRESUMO
The recurring chromosomal 1;19 translocation in acute lymphoblastic leukemia (ALL) occurs in balanced t(1;19) (q23;p13) and unbalanced, -19, +der(19)t(1;19)(q23;p13) forms. The clinical features and outcome were compared for 30 patients with the t(1;19) and 36 patients with the der(19) forms. These were 45 children (less than 1-14 years) and 21 adults (15-54 years) (median age 9.0 years), 41 females, 25 males, with median white blood count (WBC) 20.9 x 10(9)/1. Patients were classified by karyotype thus: t(1;19) 11 cases; t(1;19) with additional change (+A) 19 cases; der(19) 17 cases; and der(19) +A, 19 cases. Non-random additional structural abnormalities included involvement of 1q, 6q, i(7q), i(9q), 9p, and 13q. The only significant difference in clinical or blast cell features between patients with the t(1;19) and the der(19) was the greater age of adults with t(1;19) (p less than 0.05). Projected median event-free survival and survival of all cases together was 22 months and greater than 112 months respectively. Neither age nor WBC contributed significantly to prognosis. For patients at all ages, prognosis of der(19) was better than t(1;19). This was statistically significant for event-free and overall survival in childhood (p = 0.02 and p = 0.01 respectively) and was independent of age (p = 0.04 and p = 0.008 respectively) and WBC (p = 0.03 and p = 0.04 respectively). Future studies should examine separately the outcome for patients with the balanced and unbalanced forms of the t(1;19).
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Cariotipagem , Masculino , Pessoa de Meia-Idade , Monossomia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Estudos Retrospectivos , TrissomiaRESUMO
We sequentially performed cytogenetic analysis and RT-PCR analysis of BCR-ABL transcripts in 17 cases of Ph1-positive ALL who had achieved hematological complete remission (CR) with intensive chemotherapy (CT). Sixteen cases were studied prospectively. All but one of the patients had reached cytogenetic CR, but cytogenetic has low sensitivity in predicting relapse. Twelve patients relapsed, three died in first CR and two were alive in first CR. Two of five, two of four, and five of nine patients who were allografted (in first or second CR), autografted and received consolidation CT, respectively, achieved negative two-round PCR in the bone marrow (BM): three died in CR, three remained in CR with negative two-step PCR in the BM and three relapsed after 22 to 28 months. In all cases, relapse was preceded by switch to PCR positivity in the BM by 4 to 6 months. The remaining nine patients remained PCR-positive in the BM and relapsed after 2 to 16 months. In the four autografted cases, PCR was positive at the time of bone marrow harvest. The two patients who received a purged transplant achieved negative PCR and prolonged CR, whereas the two patients who received an unpurged transplant remained PCR positive and relapsed. In 34% of the samples where analysis was concomitant, sensitivity of PCR proved lower in the blood than in the BM. These findings show that RT-PCR is a useful tool in the monitoring of MRD in Ph1 positive ALL.
Assuntos
DNA de Neoplasias/genética , Proteínas de Fusão bcr-abl/genética , Proteínas de Neoplasias/genética , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , RNA Mensageiro/análise , RNA Neoplásico/análise , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Transplante de Medula Óssea , Criança , Seguimentos , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , RNA Mensageiro/sangue , RNA Neoplásico/sangue , Recidiva , Sensibilidade e Especificidade , Falha de TratamentoRESUMO
We present here the long-term results of three randomized clinical trials conducted on children with newly diagnosed acute lymphoblastic leukemia (ALL) between 1983 and 1998 by the Children Leukemia Cooperative Group (CLCG) from EORTC. In study 58831/32, the overall event-free survival (EFS) rates (+/- s.e.) at 6 and 10 years were 66% +/- 1.8% and 65% +/- 1.8%, respectively, and the risk of isolated central nervous system (CNS) relapse was 6% +/- 1% and 7% +/- 1%, respectively. In patients with a standard risk of relapse the omission of cyclophosphamide had no adverse effect on disease-free survival rates at 10 years (trial 58831). In medium- and high-risk patients the omission of radiotherapy did not increase the risk of CNS or systemic relapse (trial 58832). In study 58881 (1989-1998) the overall EFS rate at 8 years was 68.4% +/- 1.2% and the risk of isolated CNS relapse was 4.2%+/-0.5%. In this trial which adressed three randomized questions, the following results were obtained: the combination of cytarabine at high doses with methotrexate at high doses during interval therapy did not improve prognosis. The addition of 6-mercaptopurine iv during maintenance increased the risk of late relapse. E. coli asparaginase was more toxic and has a higher efficacy than Erwinia asparaginase. Leukocyte counts >100 x 10(9)/l, specific genetic abnormalities, a poor initial response to steroids or a high level of minimal residual disease at early time points were consistently associated with an adverse prognosis in the 58881 trial.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Intervalo Livre de Doença , Humanos , Prognóstico , Recidiva , Indução de RemissãoRESUMO
We report two pediatric cases of superior vena cava thrombosis (VTE) in patients treated for primary mediastinal large B-cell lymphoma (PMBCL). PMBCL is a rare entity in children and adolescents and no thrombosis has been described in this population. Thrombosis in lymphoma is frequently asymptomatic, detected as an incidental finding in the first months following diagnosis. The thrombosis mechanisms are often multifactorial based on veinous compression by the mass, elevated risk of thrombosis in neoplasia, and/or presence of a central catheter. The risk factors of venous thromboembolism (VTE) in lymphoma are high-grade lymphoma, comorbidities, central nervous system lymphoma, and mediastinal mass. Because thrombosis has an impact on prognosis and treatment, it seems important to improve knowledge in order to improve the diagnosis and prevention of thrombosis in lymphoma.
Assuntos
Linfoma Difuso de Grandes Células B/complicações , Neoplasias do Mediastino/complicações , Síndrome da Veia Cava Superior/etiologia , Adolescente , Feminino , Humanos , Radiografia , Síndrome da Veia Cava Superior/diagnóstico por imagemRESUMO
To evaluate the nutritional consequences of acute lymphoblastic leukemia and its treatment, 15 children with leukemia were studied. Anthropometric data, fat-free mass by impedance, energy intake, and resting energy expenditure (REE) were determined at diagnosis and on days 22, 36, and 71 of the treatment. Interleukin (IL)-1 beta, IL-6, interferon-gamma, and tumor necrosis factor were also measured. Fifteen healthy control subjects were matched for age and sex. Body weight and height and body composition were comparable at all times of the study, although three children were underweight at diagnosis (weight-for-height < 85% of French standards). Although two different methods were used for dietary recall in the two groups, energy intake expressed as a percentage of normal recommended values for age and sex was lower in patients than in control subjects (104 +/- 19%) on day 1 (47 +/- 32.1%) and day 22 (58 +/- 24%), but was comparable on day 36 (85 +/- 71%) and day 71 (85 +/- 48%). This low energy intake involved both carbohydrates and fats. Energy and carbohydrate intakes improved significantly during the study in patients. The nonprotein respiratory quotient (RQ) in patients was significantly lower than in control subjects (0.84 +/- 0.04) on day 1 (0.79 +/- 0.02) but was comparable on day 71. The REE of the patients on day 1 (5057.8 +/- 1588.4 kJ/24 h) and day 71 (4844.7 +/- 116.1 kJ/24 h) and of the control subjects (4313.8 +/- 823.5 kJ/24 h) was not significantly different. Cytokines remained undetectable on days 1, 36, and 71. The results showed that at the time of diagnosis and during this period of chemotherapy there was no evidence of raised REE. The poor intakes during the first month of chemotherapy were recent as shown by the parents' questionnaire responses and the absence of consequences in body composition. The transient decrease in RQ seemed to be an adaptative mechanism to the poor carbohydrate intake. No indication of undernutrition in the patients as a group was evident during the first 71 d of treatment although further long-term nutritional assessment is needed.
Assuntos
Metabolismo Energético/fisiologia , Estado Nutricional , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Antropometria , Estatura/fisiologia , Peso Corporal/fisiologia , Criança , Pré-Escolar , Feminino , Humanos , Interferon gama/sangue , Interleucina-1/sangue , Interleucina-6/sangue , Estudos Longitudinais , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Estudos Prospectivos , Inquéritos e Questionários , Fator de Necrose Tumoral alfa/análiseRESUMO
The objective of this study was to compare allogeneic bone marrow transplantation (BMT) with high-dose cytarabine containing chemotherapy in children with acute myeloid leukemia (AML) in first complete remission (CR). One hundred and seventy-one children were enrolled on the LAME89/91 protocol. Induction chemotherapy was a combination of cytarabine and mitoxantrone. After achieving CR, patients who had an HLA-identical sibling donor underwent allogeneic BMT. Children not eligible for BMT received post remission chemotherapy which included two consolidation courses, the second consolidation consisting of high-dose cytarabine with amsacrine and asparaginase. CR was achieved in 149 children (87%). Thirty-two had an HLA-identical sibling donor and were eligible for BMT. These 32 patients, as well as an additional child who had a one antigen HLA-mismatched father, received BMT during first CR. Consequently, 33 patients were analyzed in the BMT group and 116 in the chemotherapy group. The 4-year probability of relapse was 26 +/- 15% in the BMT group and 47 +/- 10% in the chemotherapy group (P = 0.04). The risk of therapy-related death was 3% for BMT and 7.7% for chemotherapy. Disease-free survival (DFS) was 72 +/- 15% in the BMT group and 48 +/- 10% in the chemotherapy group (p = 0.02). We conclude that allogeneic BMT from a matched sibling donor is the treatment of choice for reducing the relapse risk and for increasing DFS in children with AML in first CR.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/terapia , Amsacrina/administração & dosagem , Amsacrina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Asparaginase/administração & dosagem , Asparaginase/efeitos adversos , Transplante de Medula Óssea/mortalidade , Criança , Pré-Escolar , Terapia Combinada , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Histocompatibilidade , Humanos , Lactente , Leucemia Mieloide/mortalidade , Tábuas de Vida , Masculino , Mitoxantrona/administração & dosagem , Mitoxantrona/efeitos adversos , Núcleo Familiar , Prognóstico , Estudos Prospectivos , Indução de Remissão , Análise de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
A transient leukemoid disorder (TLD) was observed in a newborn with Down syndrome (DS), demonstrating a clonal abnormality: 47,XX,der(X;15)(p10;q10),+21(c). Spontaneous remission was observed, but 19 months later an acute leukemia from the myeloid series was discovered. Cytogenetic study revealed the same structural change as at birth, with karyotypic evolution corresponding to addition of one chromosome 8 and a fourth chromosome 21. These findings demonstrate, at least in our patient, that TLD and the subsequent acute leukemia are closely related and that TLD, closely related to DS, must be viewed as a preleukemic disorder undergoing spontaneous remission. A review of literature data shows that most cytogenetic studies reported so far are related to either TLD or acute leukemia in DS. Serial studies performed in the same patient are quite infrequent and, to the best of our knowledge, there is only one other report demonstrating a cytogenetic relation between TLD and the subsequent acute leukemia.
Assuntos
Aberrações Cromossômicas , Síndrome de Down/genética , Leucemia Mieloide/genética , Doença Aguda , Medula Óssea/fisiologia , Cromossomos Humanos Par 15 , Síndrome de Down/complicações , Feminino , Humanos , Lactente , Recém-Nascido , Cariotipagem , Leucemia Mieloide/complicações , Leucemia Mieloide/tratamento farmacológico , Cromossomo XRESUMO
We report clinical, immunologic, and cytogenetic characteristics of six patients with a t(1;19)(q23;p13) that was balanced in one case and of the unbalanced type [-19,der(19)t(1;19)(q23;p13)] in the remaining five cases. Intracytoplasmic immunoglobulins (cIg) were positive in the three cases where they were found. We also report on another patient, with a t(17;19) involving 17q11 and probably 19q13 regions, although involvement of 19p13 could not be excluded. In this patient, cIg were also present, thus raising the issue of whether such a rearrangement could be a variant of t(1;19). Clinically, five patients belonged to the high-risk acute lymphoblastic leukemia (ALL) group, because of high leukocytosis, central nervous system (CNS) disease at presentation, or massive organomegaly. Cytologically, all cases were FAB type L1. Except for the two cases allografted in the first complete remission (CR) all patients relapsed, three of them within 13 months. Two CNS relapses were seen in spite of adequate CNS prophylaxis. ALL with t(1;19) appears to be a poor-risk ALL subgroup and probably requires a reinforcement of therapeutic modalities that might include, when possible, allografting at first CR.