RESUMO
BACKGROUND: Imatinib, given concurrently or alternating with chemotherapy, has improved the response and survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) but relapses are still frequent. The aim of this study was to evaluate the feasibility and results of giving imatinib concurrently with intensive chemotherapy, stem cell transplantation and post-transplant imatinib maintenance therapy in patients with newly diagnosed Ph(+) ALL. DESIGN AND METHODS: This was a phase II study of patients with newly diagnosed Ph(+) ALL given standard chemotherapy, together with imatinib (400 mg/day) until stem cell transplantation, followed by imatinib maintenance therapy for all patients regardless of the molecular status of the disease. RESULTS: Of the 30 patients included, 27 (90%) achieved complete remission, one was resistant to treatment and two died during induction therapy. The percentages of major and complete molecular responses were 86% and 21% after induction, and 81% and 65% after consolidation, respectively. Similar results were observed assessing minimal residual disease by flow cytometry. Of the 27 patients who achieved complete remission, 21 underwent stem cell transplantation (16 allogeneic, 5 autologous). Imatinib (400 mg/day) could be administered after transplantation for a median of 3.9 months in 12 patients, although it was interrupted in 10 patients (in 2 cases because of side effects of the drug). Nine patients relapsed, four before and five after stem cell transplantation and eight patients died of transplant-related causes. With a median follow-up of 4.1 years, the probabilities (95% CI) of disease-free and overall survival were 30% (15% to 45%) and 30% (16% to 45%), respectively. CONCLUSIONS: These results confirm that imatinib is an effective first-line treatment for adult Ph(+) ALL when given concurrently with chemotherapy, making stem cell transplantation feasible in a high proportion of patients. However, post-transplantation imatinib administration was limited, mainly because of transplantation-derived complications rather than drug-specific toxicity.
Assuntos
Cromossomo Filadélfia , Piperazinas/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pirimidinas/uso terapêutico , Transplante de Células-Tronco , Adolescente , Adulto , Benzamidas , Criança , Terapia Combinada , Feminino , Seguimentos , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Estudos Prospectivos , Indução de Remissão/métodos , Transplante de Células-Tronco/mortalidade , Taxa de Sobrevida/tendências , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: About one half of adults with acute lymphoblastic leukemia are not cured of the disease and ultimately die. The objective of this study was to explore the factors influencing the outcome of adult patients with relapsed acute lymphoblastic leukemia. DESIGN AND METHODS: We analyzed the characteristics, the outcome and the prognostic factors for survival after first relapse in a series of 263 adult patients with acute lymphoblastic leukemia (excluding those with mature B-cell acute lymphoblastic leukemia) prospectively enrolled in four consecutive risk-adapted PETHEMA trials. RESULTS: The median overall survival after relapse was 4.5 months (95% CI, 4-5 months) with a 5-year overall survival of 10% (95% CI, 8%-12%); 45% of patients receiving intensive second-line treatment achieved a second complete remission and 22% (95% CI, 14%-30%) of them remained disease free at 5 years. Factors predicting a good outcome after rescue therapy were age less than 30 years (2-year overall survival of 21% versus 10% for those over 30 years old; P<0.022) and a first remission lasting more than 2 years (2-year overall survival of 36% versus 17% among those with a shorter first remission; P<0.001). Patients under 30 years old whose first complete remission lasted longer than 2 years had a 5-year overall survival of 38% (95% CI, 23%-53%) and a 5-year disease-free survival of 53% (95% CI, 34%-72%). CONCLUSIONS: The prognosis of adult patients with acute lymphoblastic leukemia who relapse is poor. Those aged less than 30 years with a first complete remission lasting longer than 2 years have reasonable possibilities of becoming long-term survivors while patients over this age or those who relapse early cannot be successfully rescued using the therapies currently available.
Assuntos
Antineoplásicos/uso terapêutico , Recidiva Local de Neoplasia/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Ensaios Clínicos como Assunto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Estudos Prospectivos , Indução de Remissão , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: T-cell acute lymphoblastic leukemia (ALL) includes 4 immunological subtypes: pro-T, pre-T, thymic or cortical and mature. In some studies, pro-T and mature subtypes have a poor prognosis. The objective of this study was to describe the clinical characteristics, the result of treatment and the prognosis of the immunological subtypes of T-cell ALL in 81 adult patients included in 2 protocols of the Spanish PETHEMA group (ALL-96 and ALL-93). PATIENTS AND METHOD: Between 1993 and 2003, 81 adult patients from 22 Spanish hospitals were included in two PETHEMA protocols: ALL-96 for standard-risk patients, and ALL-93 for high- risk patients. The main clinical and biological parameters as well as the rate of response to treatment, the frequency of complete remission , disease free survival and overall survival were compared in each T-cell ALL subtype. RESULTS: Of the 64 evaluable patients the distribution of the immunological subtypes was: 3 pro-T, 17 pre-T, 22 thymic or cortical and 22 mature. Patients with mature T-ALL had higher frequency of central nervous system involvement and myeloid antigen expression than those of the remaining subgroups. Patients with mature T-cell ALL had a slow rate of response to treatment in comparison with patients wit pre-T and mature T-cell ALL but this did not translate to significant differences in frequency of complete remission (77% vs 94%), disease free survival (42% vs 46%) and overall survival (29% vs 47%). CONCLUSIONS: Although patients with mature T-cell ALL had a slow rate of response to treatment and their survival tended to be shorter, in the present study there were no statistically significant differences in the prognosis of the different subtypes of T-cell ALL.
Assuntos
Leucemia-Linfoma de Células T do Adulto/mortalidade , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Imunofenotipagem , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/patologia , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND AND OBJECTIVES: The optimal post-remission therapy for adults with high-risk acute lymphoblastic leukemia (ALL) is not well established. This multicenter randomized trial by the Spanish PETHEMA Group was addressed to compare three options of post-remission therapy in adults with high-risk ALL: chemotherapy, allogeneic stem cell transplantation (SCT) and autologous SCT. DESIGN AND METHODS: A total of 222 valid high-risk ALL patients entered the trial. All received a standard five-drug/five-week induction course. Patients in complete remission with an HLA-identical family donor were assigned to allogeneic SCT (n=84) and the remaining were randomized to autologous SCT (n=50) or to delayed intensification followed by maintenance chemotherapy up to 2 years in complete remission (n=48). RESULTS: Overall, 183 patients achieved complete remission (82%). With a median follow-up of 70 months, the median disease-free survival and overall survival were 17 and 23 months, respectively. The 5-year disease-free survival and overall survival were 35% (95% CI, 30%-41%) and 34% (95% CI, 28%-39%), respectively. Patients allocated to the chemotherapy, allogeneic and autologous SCT were comparable in the main pre-treatment ALL characteristics and the rate of response to therapy. Intention-to-treat analysis showed no differences between patients according to whether they had or did not have a donor in disease-free survival (39%, 95% CI 30-48% vs. 33%, 95% CI 23-41%) and overall survival (44%, 95% CI 35-52% vs. 35%, 95% CI 25-44%), as well as for autologous SCT vs. chemotherapy comparisons (disease-free survival: 40%, 95% CI 28-52% vs. 51%, 95% CI 37-67%; overall survival: 43%, 95% CI 29-58% vs. 52%, 95% CI 39-65%). No differences were observed when the analysis was made on the basis of the treatment actually performed. INTERPRETATION AND CONCLUSIONS: This study failed to prove that, when a family donor is available, allogeneic SCT produces a better outcome than autologous SCT or chemotherapy in adults with high-risk ALL.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Indução de Remissão , Fatores de Risco , Transplante Autólogo , Transplante HomólogoRESUMO
BACKGROUND AND OBJECTIVE: The prognostic value of myeloid antigen expression in adult acute lymphoblastic leukemia (ALL) is controversial. The objective of this study was to evaluate the frequency and prognostic significance of myeloid antigen expression in adults with high risk ALL. PATIENTS AND METHOD: Between June 1993 and July 2002, 222 adults patients with high-risk ALL were treated according to the PETHEMA LAL 93 protocol. The frequency of myeloid antigen expression, its association with other clinical and biologic variables and the prognostic significance in terms of complete remission (CR) rate, event free survival (EFS) and overall survival (OS) were analyzed. RESULTS: Myeloid antigen expression was present in 96 out of 222 patients (43%). No association was observed between myeloid antigen expression and the main clinical and biologic characteristics of ALL. Response to treatment was slower in patients expressing myeloid antigens, but no differences were found in CR achievement, EFS or OS. The probability of EFS at 10 years for ALL patients without and with myeloid antigen expression was 35% and 34%, respectively, while the probability of OS at 10 years was 30% and 33%, respectively. This absence of differences in EFS and OS probabilities was also observed when only slow responding patients were analyzed. CONCLUSIONS: In this study, myeloid antigen expression did not have prognostic influence in adult patients with high risk ALL.
Assuntos
Antígenos CD/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Imunofenotipagem , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prevalência , Prognóstico , Análise de SobrevidaRESUMO
OBJECTIVE: Compare if localization of sounds and words discrimination in reverberant environment is different between children with dyslexia and controls. METHOD: We studied 30 children with dyslexia and 30 controls. Sound and word localization and discrimination was studied in five angles from left to right auditory fields (-90o, -45o, 0o, +45o, +90o), under reverberant and no-reverberant conditions; correct answers were compared. RESULTS: Spatial location of words in no-reverberant test was deficient in children with dyslexia at 0º and +90o. Spatial location for reverberant test was altered in children with dyslexia at all angles, except -90o. Word discrimination in no-reverberant test in children with dyslexia had a poor performance at left angles. In reverberant test, children with dyslexia exhibited deficiencies at -45o, -90o, and +45o angles. CONCLUSION: Children with dyslexia could had problems when have to locate sound, and discriminate words in extreme locations of the horizontal plane in classrooms with reverberation.
Assuntos
Dislexia/fisiopatologia , Localização de Som/fisiologia , Percepção da Fala/fisiologia , Estimulação Acústica , Audiometria/métodos , Limiar Auditivo , Estudos de Casos e Controles , Criança , Meio Ambiente , Feminino , Humanos , Masculino , Análise Multivariada , Valores de Referência , Estatísticas não Paramétricas , Fatores de Tempo , Acuidade VisualRESUMO
Phenolic acids (benzoic, phenylacetic and phenylpropionic acids) are the most abundant phenolic structures found in fecal water. As an approach towards the exploration of their action in the gut, this paper reports the antimicrobial activity of thirteen phenolic acids towards Escherichia coli, Lactobacillus spp., Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. The growth of E. coli ATCC 25922 was inhibited by only four of the phenolic acids tested at a concentration of 1000 microg/mL, whereas pathogenic E. coli O157:H7 (CECT 5947) was susceptible to ten of them. The genetically manipulated E. coli lpxC/tolC strain was highly susceptible to phenolic acids. The growth of lactobacilli (Lactobacillus paraplantarum LCH7, Lactobacillus plantarum LCH17, Lactobacillus fermentum LPH1, L. fermentum CECT 5716, Lactobacillus brevis LCH23, and Lactobacillus coryniformis CECT 5711) and pathogens (S. aureus EP167 and C. albicans MY1055) was also inhibited by phenolic acids, but to varying extents. Only P. aeruginosa PAO1 was not susceptible to any of the phenolic compounds tested. Structure-activity relationships of phenolic acids and some of their diet precursors [(+)-catechin and (-)-epicatechin] were established, based on multivariate analysis of microbial activities. The antimicrobial properties of phenolic acids reported in this paper might be relevant in vivo.
Assuntos
Antibacterianos/farmacologia , Benzoatos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Fenilacetatos/farmacologia , Fenilpropionatos/farmacologia , Antibacterianos/química , Candida albicans/efeitos dos fármacos , Farmacorresistência Bacteriana , Farmacorresistência Fúngica , Escherichia coli/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/crescimento & desenvolvimento , Humanos , Hidroxibenzoatos/química , Hidroxibenzoatos/farmacologia , Intestinos/microbiologia , Lactobacillus/efeitos dos fármacos , Probióticos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Objective Compare if localization of sounds and words discrimination in reverberant environment is different between children with dyslexia and controls. Method We studied 30 children with dyslexia and 30 controls. Sound and word localization and discrimination was studied in five angles from left to right auditory fields (-90o, -45o, 0o, +45o, +90o), under reverberant and no-reverberant conditions; correct answers were compared. Results Spatial location of words in no-reverberant test was deficient in children with dyslexia at 0º and +90o. Spatial location for reverberant test was altered in children with dyslexia at all angles, except -90o. Word discrimination in no-reverberant test in children with dyslexia had a poor performance at left angles. In reverberant test, children with dyslexia exhibited deficiencies at -45o, -90o, and +45o angles. Conclusion Children with dyslexia could had problems when have to locate sound, and discriminate words in extreme locations of the horizontal plane in classrooms with reverberation. .
Objetivo Comparar localización de sonidos y localización-discriminación de palabras bajo reverberación y sin reverberación en niños disléxicos y controles. Método Estudiamos 30 niños disléxicos y 30 controles, pareados por edad. La localización sonora y discriminación a palabras fue estudiada en cinco ángulos horizontales en los campos izquierdo y derecho (-90o, -45o, 0o, +45o, +90o), bajo reverberación y sin reverberación; las respuestas correctas fueron comparadas Resultados: La localización sonora sin reverberación fue deficiente en niños disléxicos a 0º y +90º. La localización bajo reverberación falló en niños disléxicos en todos los ángulos, excepto -90o. Durante la discriminación a palabras, sin reverberación, los niños disléxicos fallaron en ángulos izquierdos. En la prueba reverberante, los niños disléxicos fallaron a -45o, -90o y +45o. Conclusion Los niños con dislexia pueden tener problemas cuando tienen que localizar sonidos y discriminar palabras en las localizaciones extremas del plano horizontal en salones de clases típicos con reverberación. .
Assuntos
Criança , Feminino , Humanos , Masculino , Dislexia/fisiopatologia , Localização de Som/fisiologia , Percepção da Fala/fisiologia , Estimulação Acústica , Limiar Auditivo , Audiometria/métodos , Estudos de Casos e Controles , Meio Ambiente , Análise Multivariada , Valores de Referência , Estatísticas não Paramétricas , Fatores de Tempo , Acuidade VisualRESUMO
PURPOSE: The optimal postremission therapy for children with very high-risk (VHR) acute lymphoblastic leukemia (ALL) is not well established. This randomized trial compared three options of postremission therapy: chemotherapy and allogeneic or autologous stem-cell transplantation (SCT). PATIENTS AND METHODS: All 106 VHR-ALL patients received induction with five drugs followed by intensification with three cycles of chemotherapy. Patients in complete remission (CR) with an HLA-identical family donor were assigned to allogeneic SCT (n = 24) and the remaining were randomly assigned to autologous SCT (n = 38) or to delayed intensification followed by maintenance chemotherapy up to 2 years in CR (n = 38). RESULTS: Overall, 100 patients achieved CR (94%). With a median follow-up of 6.5 years, 5-year disease-free survival (DFS) and overall survival (OS) probabilities were 45% (95% CI, 37% to 54%) and 48% (95% CI, 40% to 57%), respectively. The three groups were comparable in the main pretreatment ALL characteristics. Intention-to-treat analysis showed no differences for donor versus no donor in DFS (45%; 95% CI, 27% to 65% v 45%; 95% CI, 37% to 55%) and OS (48%; 95% CI, 30% to 67% v 51%; 95% CI, 43% to 61%), as well as for autologous SCT versus chemotherapy comparisons (DFS: 44%; 95% CI, 29% to 60% v 46%; 95% CI, 32% to 62%; OS: 45%; 95% CI, 31% to 62% v 57%; 95% CI, 43% to 73%). No differences were found within the different subgroups of ALL and neither were differences observed when the analysis was made by treatment actually performed. CONCLUSION: This study failed to prove that, when a family donor is available, allogeneic SCT produces a better outcome than autologous SCT or chemotherapy in children with VHR-ALL.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transplante de Células-Tronco/métodos , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Indução de Remissão , Risco , Transplante Autólogo , Transplante Homólogo , Resultado do TratamentoRESUMO
Recurrence of acute lymphoblastic leukemia (ALL) in the central nervous system (CNS) confers a poor prognosis, although to the authors' knowledge, only a few studies have analyzed this issue in adults. For the current study, the authors analyzed the frequency, predictive factors, and prognosis of CNS involvement and recurrence in adult patients with ALL who did not receive cranial irradiation for CNS prophylaxis. Four hundred sixty-seven adult patients (age > or = 15 years) with ALL were treated on 4 protocols: ALL-89 (standard-risk and high-risk ALL; n = 108 patients), ALL-93 (high-risk ALL; n = 222 patients), ALL-96 (standard-risk ALL; n = 84 patients), and ALL3-97 (Burkitt leukemia; n = 53 patients). CNS prophylaxis consisted of intrathecal methotrexate, cytarabine, and hydrocortisone together with high-dose systemic methotrexate and cytarabine. The mean age (+/- standard deviation) was 33 years (+/- 16 years), and 272 patients were males. ALL subtypes included an early pre-B phenotype (15%), a common phenotype (45%), a pre-B phenotype (5%), a mature B phenotype (11%), and a T phenotype (24%). CNS involvement at diagnosis was observed in 18 patients (3.9%). Of 159 recurrences, 22 occurred (5.8%) in the CNS (14 isolated and 8 combined). A lactate dehydrogenase level > 1000 U/L was the only factor associated with the risk of CNS recurrence. A complete remission was attained in 7 of 22 patients (32%). The median overall survival after recurrence was 0.7 years for patients with isolated CNS recurrence, 0.13 years for patients with combined recurrence, and 0.41 years for patients with bone marrow recurrence (P = .11). The only 2 survivors underwent stem cell transplantation. The frequency of CNS recurrence in adult patients with ALL who do not receive radiotherapy for CNS prophylaxis was similar to the frequency observed in protocols that included cranial irradiation. A lactate dehydrogenase value >1000 U/L was the only factor found to be associated with CNS recurrence. The prognosis for patients who develop CNS recurrence is poor, identical to that for patients who develop bone marrow recurrence.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/patologia , Recidiva Local de Neoplasia/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Adolescente , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias do Sistema Nervoso Central/prevenção & controle , Terapia Combinada , Irradiação Craniana , Citarabina/administração & dosagem , Feminino , Humanos , Hidrocortisona/administração & dosagem , Incidência , Lactato Desidrogenases/análise , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de SobrevidaRESUMO
BACKGROUND AND OBJECTIVES: Cytogenetic analysis is one of the most reliable prognostic factors in acute lymphoblastic leukemia. The objective of this study was to analyze the prognostic value of cytogenetic analysis in children and adults with high-risk acute lymphoblastic leukemia (HR-ALL) included in a prospective multicenter trial. DESIGN AND METHODS: One hundred and thirty patients (44 children and 86 adults) with HR-ALL included in the PETHEMA ALL-93 trial had an adequate cytogenetic study after review. Cytogenetic subgroups were established according to the cancer and acute leukemia group B criteria (unfavorable: 11q23, t(9;22), -7 and +8; normal; miscellaneous: the remaining chromosome abnormalities) and their main clinicobiological features were compared. Univariable and multivariable analyses for complete remission (CR) attainment, event-free survival (EFS) and overall survival (OS) were performed. RESULTS: The mean SD age was 26 14 years. Two were infants (<1 year), 42 were children and 86 adults (19-50 years). The cytogenetic study was normal in 44 (34%) cases. The most frequent chromosomal rearrangement was t(9;22)(q34;q11) (34 cases, 26%, 30 adults), followed by 11q23 (12 cases, 9% -8 children-, including t(4;11)(q21;q23) in 8, 7 children). Patients with t(9;22) were older than the remaining cases, whereas those with 11q23 rearrangements were younger and had higher WBC counts. Multivariable analyses showed two associated factors in adults with a lower frequency of CR and a shorter EFS and OS: t(9;22) and slow response to therapy (assessed by a percentage of blast cells higher than 10% in bone marrow study on day 14). For children with very high-risk ALL, only slow response to therapy (assessed by the presence of blast cells in peripheral blood on day 8) was associated with a negative impact on CR, EFS and OS. INTERPRETATION AND CONCLUSIONS: In adult patients with high-risk acute lymphoblastic leukemia included in the PETHEMA ALL-93 protocol, cytogenetic analysis at diagnosis is a useful independent prognostic marker. The poorest prognosis for patients with t(9;22) justifies the development of specific treatments for these patients. In this small subgroup of children with very high-risk ALL no cytogenetic characteristics was found to influence the results of therapy, slow response to therapy being the only prognostic factor.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aberrações Cromossômicas , Cariotipagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Medula Óssea/patologia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Estudos Prospectivos , Indução de Remissão , Análise de Sobrevida , Translocação Genética , Resultado do TratamentoAssuntos
Antineoplásicos/efeitos adversos , Cromossomo Filadélfia , Piperazinas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pirimidinas/efeitos adversos , Dermatopatias/induzido quimicamente , Idoso , Benzamidas , Feminino , Humanos , Mesilato de ImatinibRESUMO
Fundamento y objetivo: La leucemia aguda linfoblástica (LAL) de fenotipo T incluye 4 subtipos inmunológicos: pro-T, pre-T, tímica o cortical y madura. En algunos estudios, los subtipos LAL pro-T y maduro tienen un peor pronóstico. El objetivo de este estudio ha sido describir las principales características clínicas, los resultados del tratamiento y el pronóstico de los subtipos inmunológicos de LAL-T en 81 pacientes adultos incluidos en 2 protocolos del grupo PETHEMA (LAL-96 y LAL-93). Pacientes y método: Entre 1993 y 2003, se incluyó en 2 protocolos de PETHEMA a 81 pacientes adultos de 22 hospitales españoles: LAL-96 para pacientes de riesgo estándar y LAL-93 para pacientes de alto riesgo. Se comparó los principales parámetros clínicos y biológicos iniciales de cada subgrupo de LAL-T, así como la rapidez en la respuesta al tratamiento, la tasa de remisión completa, la supervivencia libre de enfermedad y la supervivencia global. Resultados: De los 64 pacientes evaluables, la distribución de los subtipos inmunológicos fue: 3 pro-T, 17 pre-T, 22 tímica o cortical y 22 madura. Los pacientes con LAL-T madura presentaron afección inicial del sistema nervioso central y marcadores mieloides con mayor frecuencia que el resto de los pacientes. Los pacientes con LAL-T madura tuvieron una respuesta significativamente más lenta al tratamiento que los que presentaban LAL-T pre-T y cortical, pero ello no se tradujo en diferencias significativas en la tasa de remisión completa (el 77 frente al 94%) supervivencia libre de enfermedad (el 42 frente al 46%) y la supervivencia global (el 29 frente al 47%). Conclusiones: Aunque los pacientes con LAL-T madura respondieron más lentamente al tratamiento y su supervivencia tendió a ser más corta, en el presente estudio no se encontraron diferencias estadísticamente significativas en el pronóstico de los diferentes subtipos de LAL-T
Background and objective: T-cell acute lymphoblastic leukemia (ALL) includes 4 immunological subtypes: pro-T, pre-T, thymic or cortical and mature. In some studies, pro-T and mature subtypes have a poor prognosis. The objective of this study was to describe the clinical characteristics, the result of treatment and the prognosis of the immunological subtypes of T-cell ALL in 81 adult patients included in 2 protocols of the Spanish PETHEMA group (ALL-96 and ALL-93). Patients and method: Between 1993 and 2003, 81 adult patients from 22 Spanish hospitals were included in two PETHEMA protocols: ALL-96 for standard-risk patients, and ALL-93 for high- risk patients. The main clinical and biological parameters as well as the rate of response to treatment, the frequency of complete remission , disease free survival and overall survival were compared in each T-cell ALL subtype. Results: Of the 64 evaluable patients the distribution of the immunological subtypes was: 3 pro-T, 17 pre-T, 22 thymic or cortical and 22 mature. Patients with mature T-ALL had higher frequency of central nevous system involvement and myeloid antigen expression than those of the remaining subgroups. Patients with mature T-cell ALL had a slow rate of response to treatment in comparison with patients wit pre-T and mature T-cell ALL but this did not translate to significant differences in frequency of complete remission (77% vs 94%), disease free survival (42% vs 46%) and overall survival (29% vs 47%). Conclusions: Although patients with mature T-cell ALL had a slow rate of response to treatment and their survival tended to be shorter, in the present study there were no statistically significant differences in the prognosis of the different subtypes of T-cell ALL
Assuntos
Masculino , Feminino , Adulto , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/imunologia , Prognóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/classificação , Protocolos Clínicos , Biomarcadores/análise , Citometria de Fluxo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/classificação , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológicoRESUMO
Fundamento y objetivo: El valor pronóstico de los marcadores mieloides en la leucemia aguda linfoblástica (LAL) del adulto es controvertido. El objetivo de este estudio fue evaluar la frecuencia y el significado pronóstico de los marcadores mieloides en adultos con LAL de alto riesgo. Pacientes y método: Entre junio de 1993 y julio de 2002, 222 pacientes adultos con LAL de alto riesgo se trataron según el protocolo PETHEMA LAL 93. Se analizó la frecuencia de los marcadores mieloides, su asociación con otras variables clínico-biológicas de la LAL y el significado pronóstico expresado como la probabilidad de obtención de la remisión completa (RC), supervivencia libre de evento (SLE) y supervivencia global (SG). Resultados: La presencia de marcadores mieloides se constató en 96 de los 222 pacientes (43%). No se observó ninguna relación entre la presencia de marcadores mieloides y las principales características clínico-biológicas de la LAL. La rapidez de la respuesta al tratamiento fue menor en los pacientes con marcadores mieloides, pero no se hallaron diferencias en la tasa de obtención de la RC, la SLE y la SG. La probabilidad de SLE a los 10 años fue, respectivamente, del 35 y del 34% para las LAL con marcadores mieloides y sin ellos. La probabilidad de SG a los 10 años fue del 33% para las LAL con marcadores mieloides y del 30% para las que no los presentaban. Cuando se estudiaron de manera aislada los pacientes con respuesta lenta al tratamiento, tampoco se hallaron diferencias en términos de SLE y SG entre ambos tipos de LAL. Conclusiones: En este estudio los marcadores mieloides no tuvieron significado pronóstico en los pacientes adultos con LAL de alto riesgo
Background and objective: The prognostic value of myeloid antigen expression in adult acute lymphoblastic leukemia (ALL) is controversial. The objective of this study was to evaluate the frequency and prognostic significance of myeloid antigen expression in adults with high risk ALL. Patients and method: Between June 1993 and July 2002, 222 adults patients with high-risk ALL were treated according to the PETHEMA LAL 93 protocol. The frequency of myeloid antigen expression, its association with other clinical and biologic variables and the prognostic significance in terms of complete remission (CR) rate, event free survival (EFS) and overall survival (OS) were analyzed. Results: Myeloid antigen expression was present in 96 out of 222 patients (43%). No association was observed between myeloid antigen expression and the main clinical and biologic characteristics of ALL. Response to treatment was slower in patients expressing myeloid antigens, but no differences were found in CR achievement, EFS or OS. The probability of EFS at 10 years for ALL patients without and with myeloid antigen expression was 35% and 34%, respectively, while the probability of OS at 10 years was 30% and 33%, respectively. This absence of differences in EFS and OS probabilities was also observed when only slow responding patients were analyzed. Conclusions: In this study, myeloid antigen expression did not have prognostic influence in adult patients with high risk ALL