Perfil epidemiológico, incidência, mortalidade e sobrevida de crianças e adolescentes com leucemias em Pernambuco / Epidemiological Profile, Incidence, Mortality, and Survival of Children and Adolescents Diagnosed with Leukemia in Pernambuco, Brazil

Introdução: Leucemia é o câncer mais comum em crianças e a principal causa de óbito relacionada ao câncer na infância. A sobrevida das crianças com leucemia tem melhorado de forma significativa, entretanto, ainda permanece abaixo de 50% na maioria dos países com recursos limitados. Objetivo: Descrever o perfil epidemiológico, incidência, mortalidade, sobrevida das leucemias agudas e os fatores de risco para o óbito em crianças e adolescentes com leucemia mieloide aguda (LMA) em Pernambuco. Metodologia: a) coorte retrospectiva com crianças e adolescentes (0-19 anos), a partir das informações do Registro de Câncer de Base populacional (RCBP) do Recife (período de 1998 - 2007). As tendências da incidência e da mortalidade foram avaliadas utilizando-se o método Joinpoint. A sobrevida relativa foi calculada, utilizando-se a tábua completa de mortalidade disponível no Instituto Brasileiro de Geografia Estatística (IBGE) para o Brasil em 2010. b) Foram analisados o risco cumulativo de óbito precoce (até 6 semanas do diagnóstico) e a sobrevida global (SG) e livre de eventos (recidiva, segunda neoplasia ou óbito) pelo método de Kaplan Meier para leucemia promielocítica aguda (LPA), LMA da síndrome de Down (LMA-SD) e outros subtipos (exceto LMASD e LPA) e os fatores preditivos para o óbito, por características do diagnóstico utilizando-se a regressão multivariada de Cox, distintamente para leucemia promielocítica aguda (LPA) e para outros subtipos de LMA a partir de uma coorte de crianças diagnosticadas entre 2000-2014 com LMA e acompanhadas no Instituto de Medicina Integral Prof. Fernando Figueira (IMIP). Resultados: a) o estudo de base populacional envolveu 175 casos. A taxa de incidência para leucemias foi de 41,1/milhão de habitantes menores de 20 anos, com pico de incidência de 78,3/milhão na faixa de 1 a 4 anos....

Introduction Leukemia is the most common cancer in children and the leading cause of cancerrelateddeath in childhood, with a variable incidence worldwide. The survival rates for children with leukemia have significantly improved. However, it remains below 50% in most countries with limited resources. Objective The aim of the study was to describe the epidemiological profile, incidence,mortality, survival, and risk factors for death in children and adolescents with acute myeloid leukemia (AML) in Pernambuco, Brazil. Methodology Two studies were conducted. a) The first study included a retrospective cohort of children and adolescents aged 0–19 years, based on the data obtained fromthe population-based cancer registry in Recife (1998–2007). Joinpoint method was used to evaluate the incidence and mortality trends. The relative survival was calculated using the complete mortality table available at the Instituto Brasileiro de Geografia e Estatística for Brazil in 2010. b) The second study included a cohort of children who were diagnosed with AML between 2000 and 2014 and treated at the Instituto de Medicina Integral Prof. Fernando Figueira - IMIP. The cumulative risk ofearly death (until 6 weeks of diagnosis), overall survival (OS), and event-free survival (EFS) considered as recurrence, second neoplasia, or death for acute promyelocytic leukemia (APL), AML with Down syndrome (AML-DS), and other subtypes (except AML-DS and APL) were analyzed using the Kaplan-Meier method. Cox multivariate regression model was used to identify factors predictive of death, by the characteristics of the diagnosis, distinctly for APL and for the othersubtypes of AML...

Outcome of children and adolescents with lymphoblastic lymphoma / Evolução de crianças e adolescentes com linfoma linfoblástico

SUMMARY Introduction: lymphoblastic lymphoma (LBL) is the second most common subtype of non-Hodgkin lymphoma in children. The aim of this study was to characterize the clinical course of children and adolescents with LBL treated at a tertiary center. Methods: this is a retrospective cohort study of 27 patients aged 16 years or less with LBL admitted between January 1981 and December 2013. Patients received intensive chemotherapy regimen derived from acute lymphoblastic leukemia (ALL) therapy. Diagnosis was based on biopsy of tumor and/or cytological examination of pleural effusions. The overall survival was analyzed using the Kaplan-Meier method. Results: the median age at diagnosis was 11.6 years (interquartile range, 4.6-13.8). LBL had T cell origin in 16 patients (59%). The most common primary manifestation in T-cell LBL was mediastinum involvement in 9 patients (56%). Intra-abdominal tumor was the major site of involvement in patients with pB-LBL. Most patients had advanced disease (18 patients - 67%) at diagnosis. Twenty-four patients (89%) achieved complete clinical remission. After a median follow-up of 43 months (interquartile range, 6.4-95), 22 patients (81%) were alive in first complete remission. Five children (18.5%) died, three of them soon after admission and two after relapsing. The probability of survival at five years for 20 patients with de novo LBL was 78% (SD 9.4). Conclusion: our findings confirm the favorable prognosis of children with LBL with an intensive chemotherapy regimen derived from ALL therapy.

RESUMO Objetivos: linfoma linfoblástico (LL) é o segundo subtipo mais comum de linfoma não Hodgkin em crianças. O objetivo deste estudo foi caracterizar a evolução clínica de crianças e adolescentes com LL em um centro terciário. Métodos: estudo de coorte retrospectivo de 27 pacientes com idade de até 16 anos com LL admitidos entre janeiro de 1981 e dezembro de 2013. Os pacientes foram tratados de acordo com o protocolo de tratamento para leucemia linfoblástica aguda (LLA). O diagnóstico foi baseado em biópsia do tumor e/ou no exame citológico de derrame pleural. A sobrevida global foi analisada pelo método de Kaplan-Meier. Resultados: a média de idade ao diagnóstico foi de 11,6 anos (variação interquartil, 4,6-13,8). LL de células T foi identificado em 16 pacientes (59%) e a manifestação primária mais comum foi o acometimento mediastinal em 9 pacientes (56%). Tumor intra-abdominal foi a manifestação clínica principal nos pacientes com LL de células pré-B. A maioria dos pacientes apresentava doença avançada (18 pacientes - 67%) ao diagnóstico. Vinte e quatro pacientes (89%) alcançaram remissão clínica completa. Após um período de acompanhamento médio de 43 meses (intervalo interquartil, 6,4-95), 22 pacientes (81%) continuam vivos em primeira remissão clínica completa. Cinco crianças (18,5%) morreram, três delas logo após a admissão e duas após recidiva. A probabilidade de sobrevida em cinco anos para 20 pacientes com LL de novo foi de 78% (SD 9.4). Conclusão: nossos resultados confirmam o prognóstico favorável de crianças com LL tratadas com regime de quimioterapia intensiva derivado da terapia de LLA.

Outcome of children and adolescents with lymphoblastic lymphoma / Evolução de crianças e adolescentes com linfoma linfoblástico

Summary Introduction: lymphoblastic lymphoma (LBL) is the second most common subtype of non-Hodgkin lymphoma in children. The aim of this study was to characterize the clinical course of children and adolescents with LBL treated at a tertiary center. Methods: this is a retrospective cohort study of 27 patients aged 16 years or younger with LBL admitted between January 1981 and December 2013. Patients were treated according to the therapy protocol used for acute lymphoblastic leucemia. Diagnosis was based on biopsy of tumor and/or cytological examination of pleural effusions. The overall survival was analyzed using the Kaplan-Meier method. Results: the median age at diagnosis was 11.6 years (interquartile range, 4.6- 13.8). LBL had T-cell origin in 16 patients (59%). The most common primary manifestation in T-cell LBL was mediastinal involvement, in 9 patients (56%). Intra-abdominal tumor was the major site of involvement in patients with precursor B-LBL. Most patients had advanced disease (18 patients – 67%) at diagnosis. Twenty-four patients (89%) achieved complete clinical remission. After a median follow-up of 43 months (interquartile range, 6.4-95), 22 patients (81%) were alive in first complete remission. Five children (18.5%) died, three of them soon after admission and two after relapsing. The probability of survival at five years for 20 patients with de novo LBL was 78% (SD 9.4). Conclusion: our findings confirm the favorable prognosis of children with LBL with an intensive chemotherapy regimen derived from ALL therapy.

Resumo Objetivos: linfoma linfoblástico (LL) é o segundo subtipo mais comum de linfoma não Hodgkin em crianças. O objetivo deste estudo foi caracterizar a evolução clínica de crianças e adolescentes com LL em um centro terciário. Métodos: estudo de coorte retrospectivo de 27 pacientes com idade de até 16 anos com LL admitidos entre janeiro de 1981 e dezembro de 2013. Os pacientes foram tratados de acordo com o protocolo de tratamento para leucemia linfoblástica aguda (LLA). O diagnóstico foi baseado em biópsia do tumor e/ou no exame citológico de derrame pleural. A sobrevida global foi analisada pelo método de Kaplan-Meier. Resultados: a média de idade ao diagnóstico foi de 11,6 anos (variação interquartil, 4,6-13,8). Linfoma linfoblástico de células T foi identificado em 16 pacientes (59%) e a manifestação primária mais comum foi o acometimento mediastinal (56%). Tumor intra-abdominal foi a manifestação clínica principal nos pacientes com LL de células pré- -B. A maioria dos pacientes apresentava doença avançada (18 pacientes, 67%) ao diagnóstico. Vinte e quatro pacientes (89%) alcançaram remissão clínica completa. Após um período de acompanhamento médio de 43 meses (intervalo interquartil, 6,4-95), 22 pacientes (81%) continuam vivos em primeira remissão clínica completa. Cinco crianças (18,5%) morreram, três delas logo após a admissão e duas após recidiva. A probabilidade de sobrevida em cinco anos para 20 pacientes com LL de novo foi de 78% (DP 9,4). Conclusão: os resultados confirmam o prognóstico favorável de crianças com LL tratadas com regime de quimioterapia intensiva derivado da terapia de LLA.

Relationship between complaints presented by emergency patients and the final outcome / Relação entre queixas apresentadas por pacientes na urgência e o desfecho final / Relación entre las quejas presentadas por pacientes en la urgencia y el desenlace final

AbstractObjective: to relate complaints presented by emergency room patients, classified using the Manchester Triage System, with the final outcome (discharge/death/transfer).Methods: prospective cohort study, involving 509 patients who were admitted to the emergency room and remained there for more than 24 hours after admission, being monitored to the final outcome. Data were analyzed with a statistical program using descriptive and analytical statistics.Results: the mean age of the patients was 59.1 years and 59.3% were male. The main complaints were unwell adult (130 - 22.5%), shortness of breath in adults (81 - 14.0%), abdominal pain in adults (58 - 10.0%) and behaving strangely (34 - 5.9%), with 87% of the patients being discharged. More deaths were found in the patients classified in the severe colors, with 42.8% classified as red, 17.0% as orange and 8.9% as yellow. Among the patients classified as green, 9.6% died.Conclusion: in the various colors of the Manchester Triage System, death prevailed in patients that presented the complaints of unwell adult, shortness of breath, head injury, major trauma, diarrhea and vomiting. The higher the clinical priority the greater the prevalence of death.

ResumoObjetivo:relacionar queixas apresentadas pelos pacientes classificados pelo Sistema de Triagem de Manchester em um pronto-socorro com o desfecho final (alta/óbito/transferência).Métodos:estudo de coorte prospectivo, realizado com 509 pacientes que deram entrada no pronto-socorro e que nele permaneceram por mais de 24 horas após a admissão, sendo acompanhados até o desfecho final. Os dados foram digitados e analisados com estatística descritiva e analítica em um pacote estatístico.Resultados:entre os pacientes, 59,3% eram do sexo masculino, com idade média de 59,1 anos. As queixas principais eram de mal-estar no adulto (130-22,5%), dispneia em adulto (81-14,0%), dor abdominal em adulto (58-10,0%), alterações de comportamento (34-5,9%), sendo que, desses, 87% recebeu alta. Foram encontrados mais óbitos nos pacientes classificados nas cores mais graves, sendo 42,8% classificados como vermelho, 17,0% laranja e 8,9% como amarelo. Entre os pacientes classificados como verde, 9,6% evoluiu para óbito.Conclusão:nas diversas cores do Sistema de Triagem Manchester, o óbito prevaleceu nos pacientes que apresentaram a queixa de mal-estar no adulto, dispneia, sofreram trauma craniano, trauma maior, diarreia e vômito. Quanto maior a prioridade clínica maior a prevalência de óbito.

ResumenObjetivo:relacionar las quejas presentadas por los pacientes clasificados por el Sistema de Clasificación de Manchester, en un servicio de urgencia, con el desenlace final (alta/muerte/ transferencia).Métodos:estudio de cohorte prospectiva, realizado con 509 pacientes que dieron entrada en el servicio de urgencia y que en él permanecieron por más de 24 horas después de la admisión, siendo seguidos hasta el desenlace final. Los datos fueron introducidos y analizados con estadística descriptiva y analítica, en un programa estadístico.Resultados:entre los pacientes, 59,3% eran del sexo masculino, con edad promedio de 59,1 años. Las quejas principales eran de malestar en adulto (130-22,5%), disnea en adulto (81-14,0%), dolor abdominal en adulto (58- 10,0%), alteraciones de comportamiento (34-5,9%), siendo que, de estos, 87% recibió alta. Fueron encontradas más muertes entre los pacientes clasificados con los colores más graves, siendo 42,8% clasificados como rojo, 17,0% naranja y 8,9% como amarillo. Entre los pacientes clasificados como verde, 9,6% evolucionó para la muerte.Conclusión:en los diversos colores del Sistema de Clasificación Manchester, la muerte prevaleció en los pacientes que presentaron la queja de malestar en adulto, disnea, sufrieron trauma craniano, trauma mayor, diarrea y vómito. Cuanto mayor es la prioridad clínica mayor es la prevalencia de la muerte.

Neurocognitive Outcome in Survivors of Childhood Acute Lymphoblastic Leukemia: Experience at a Tertiary Care Hospital in Korea

This study was conducted to investigate long-term neurocognitive outcomes and to determine associated risk factors in a cohort of Korean survivors of childhood acute lymphoblastic leukemia (ALL). Forty-two survivors of ALL were compared with 42 healthy controls on measures of a neurocognitive test battery. We analysed potential risk factors (cranial irradiation, sex, age at diagnosis, elapsed time from diagnosis, and ALL risk group) on neurocognitive outcomes. ALL patients had lower, but non-significant full-scale intelligence quotient (FSIQ, 107.2 +/- 12.2 vs. 111.7 +/- 10.2), verbal intelligence quotient (VIQ, 107.7 +/- 13.6 vs. 112.2 +/- 11.4), and performance intelligence quotient (PIQ, 106.3 +/- 14.2 vs. 110.1 +/- 10.7) scores than healthy controls. However, patients treated with cranial irradiation performed significantly lower on FSIQ (102.2 +/- 8.1), VIQ (103.3 +/- 11.7), and PIQ (101.4 +/- 13.2) compared to non-irradiated patients and healthy controls. ALL patients also had poor attention, concentration, and executive functions. Among ALL survivors, cranial irradiation was a risk factor for poor FSIQ, being male was a risk factor for poor PIQ, and younger age was a risk factor for poor attention. Therefore, the delayed cognitive effects of ALL treatment and its impact on quality of life require continuing monitoring and management.

NRAS Mutations in de novo acute leukemia: Prevalence and clinical significance.

The activating mutations of the Ras gene or other abnormalities in Ras signaling pathway lead to uncontrolled growth factor-independent proliferation of hematopoietic progenitors. Oncogenic mutations in NRAS gene have been observed with variable prevalence in hematopoietic malignancies. In the present study, NRAS mutations were detected using bidirectional sequencing in 264 acute leukemia cases — 129 acute lymphocytic leukemia (ALL) and 135 acute myeloid leukemia (AML) and 245 age- and gender-matched controls. Missense mutation was observed only in the 12th codon of NRAS gene in 4.7% of AML and 3.16% of ALL cases. The presence of NRAS mutation did not significantly influence blast % and lactate dehydrogenase (LDH) levels in AML patients. When the data were analyzed with respect to clinical variables, the total leukocyte count was elevated for mutation positive group, compared to negative group. In AML patients with NRAS mutations, 60% failed to achieve complete remission (CR), as compared to 34.8% in mutation negative group. These results indicated that NRAS mutations might confer poor drug response. In AML, disease free survival (DFS) in NRAS mutation positive group was lesser, compared to mutation negative group (9.5 months vs. 11.68 months). In ALL patients, DFS of NRAS mutation positive group was lesser than mutation negative group (9.2 months vs. 27.5 months). The CR rate was also lower for mutation-positive patients group, compared to mutation-negative group. In conclusion, these results suggested that presence of NRAS mutation at 12th codon was associated with poor response and poorer DFS in both ALL and AML.

Leucemia linfoblástica aguda em lactentes: 20 anos de experiência / Acute lymphoblastic leukemia in infants: 20 years of experience

OBJETIVO: Analisar pacientes com menos de dois anos de idade com leucemia linfoblástica aguda atendidos no período de 1990 a 2010, em um centro de referência estadual. MÉTODOS: Estudo clínico, epidemiológico, transversal, descritivo e observacional. Pacientes incluídos tinham menos de dois anos de idade, com leucemia linfoblástica aguda, tratados no período de 1990 a 2010 na unidade de oncologia pediátrica de um centro de referência estadual, totalizando 41 casos. RESULTADOS: Todos os pacientes eram Caucasianos e 60,9% eram do sexo feminino. Com relação à idade, 24,38% tinham menos de seis meses, 17,07% tinham entre seis meses e um ano e 58,53% mais do que um ano de idade. A idade de seis meses foi estatisticamente significante para o desfecho de óbito. Os sinais e sintomas predominantes foram febre, hematomas e petéquias. Uma contagem de leucócitos superior a 100.000 foi observada em 34,14% dos casos; hemoglobina inferior a 11 em 95,13% e contagem de plaquetas inferior a 100.000, em 75,61% dos casos. Infiltração do sistema nervoso central estava presente em 12,91% dos pacientes. Em relação à linhagem, a linhagem B predominou (73%), mas a linhagem de células T foi estatisticamente significativa para o óbito. Trinta e nove por cento dos pacientes tiveram recorrência da doença. Em relação ao estado vital, 70,73% dos pacientes morreram, sendo choque séptico a principal causa. CONCLUSÕES: leucemia linfoblástica aguda em crianças tem uma alta taxa de mortalidade, principalmente em crianças menores de um ano e linhagem derivada de células T.

OBJECTIVE: To analyze patients younger than 2 years with acute lymphoblastic leukemia, treated in the period between 1990 and 2010 in a state reference center. METHODS: This was a clinical-epidemiological, cross-sectional, observational, and descriptive study. It included patients younger than 2 years with acute lymphoblastic leukemia, treated in the period of 1990 to 2010 in a pediatric oncology unit of a state reference center, totaling 41 cases. RESULTS: All patients were white ethnicity, and 60.9% were females. Regarding age, 24.38% were younger than 6 months, 17.07% were between 6 months and 1 year, and 58.53% were older than 1 year. The age of 6 months was statistically significant for the outcome of death. Predominant signs and symptoms were fever, bruising, and petechiae. A leukocyte count > 100,000 was found in 34.14% of cases, hemoglobin count < 11 in 95.13%, and platelet count < 100,000 in 75.61. Infiltration of central nervous system was present in 12.91% of patients. According to the lineage, B-cell lineage predominated (73%), but the T-cell line was statistically significant for death. 39% of patients had disease recurrence. In relation to vital status, 70.73% of the patients died; septic shock was the main cause. CONCLUSIONS: Acute lymphoblastic leukemia in infants has a high mortality rate, especially in children under 1 year and those with T-cell derived lineage.

Tratamiento de la leucemia linfoide aguda del adulto: Experiencia de un hospital en la Ciudad de México / Results of treatment of acute lymphoblastic leukemia in two cohorts of Mexican patients

Background: GIMEMA ALL 0288 trial was designed to evaluate the impact of a 7-day prednisone (PDN) pretreatment on complete remission of acute lymphoblastic leukemia. We adopted this trial in 2007. Aim: To evaluate the results of treatment in two cohorts of patients with acute lymphoblastic leukemia, treated from 2007 to January 2009 and from February to December 2009. Material and Methods: We studied 99 patients treated in the first period (58 males) and 54 patients treated in the second period (33 males) The age of patients ranged from 16 to 60 years and 70 percent of patients were of high risk. BCR/ABL fusion transcript was present in 12 percent of patients. Results: Remission rates were 61 and 51 percent for patients of the first and second group of treatment, respectively. The main cause of death were infections during the induction period. There were 49 relapses, mainly detected in the blood marrow. Global and event free 34 months survival were 32 and 30 percent respectively. Multivariate analysis disclosed risk stratification and central nervous system infiltration as risk factors for mortality. Conclusions: The main obstacles for the treatment of acute lymphoblastic leukemia in these cohorts of patients were the high incidence of infections and the lack of use of growth stimulating factors.

Recidiva da leucemia linfoblástica na criança: experiência do Serviço de Hematologia do Hospital das Clínicas da UFMG (1988-2005) / Relapse of acute lymphoblastic leukemia in child: experience of the Division of Hematology: Hospital das Clínicas da UFMG(1988-2005)

Objetivos: Analisar a evolução de crianças com primeira recidiva da leucemia linfoblástica (LLA) e identificar fatores prognósticos para segunda recidiva ou óbito. Métodos: Análise retrospectiva de 95 pacientes com recidiva da LLA tratados no Hospital das Clínicas, Universidade Federal de Minas Gerais, Brasil, entre 1988 e 2005. Resultados: A idade ao diagnostico inicial variou de 3 meses a 15,2 anos (mediana de 6 anos); 53 crianças eram do sexo masculino. A recaída medular isolada ou combinada ocorreu em 81% dos casos e a recaída extramedular isolada em 19%. Sessenta crianças alcançaram a segunda remissão. Todas foram submetidas ao tratamento com drogas citostáticas e em nenhuma criança com LLA em segunda remissão foi feito transplante de medula óssea. A probabilidade estimada de sobrevida global em 10 anos para todo o grupo foi de 16,1% (IC 95%: 9,3% - 24,6%). O óbito ocorreu em 77 crianças e a doença em atividade foi a principal causa. Os pacientes foram estratificados em 3 subgrupos: recidiva muito precoce (primeiros 18 meses desde o diagnóstico inicial), recidiva precoce (entre 18 e 30 meses) e recidiva tardia (mais de 30 meses após a data do diagnóstico inicial). A probabilidade estimada de sobrevida livre de eventos em 10 anos para cada um desses grupos foram, respectivamente, 2,2% (IC 95%: 0,2%-10%), 12,5% (IC 95%: 3,1%-28,7%) e 32,5% (IC 95%: 14,6%-51,9%; p< 0001). Conclusões: A duração da primeira remissão foi a única variável estatisticamente significativa que influenciou o prognóstico das crianças com recidiva da LLA.

Objectives: To follow up children in first relapse of acute lymphoblastic leukemia (ALL) and to identify prognostic factors for a second relapse or death. Methods: Retrospective analysis of 95 patients with relapse of ALL followed at Hospital das Clínicas, Universidade Federal de Minas Gerais, Brazil, between 1988 and 2005. Results: The age at initial diagnosis varied from 3 months to 15.2 years (median 6 y); 53 were male. Isolated or combined marrow relapse occurred in 81% of cases and isolated extramedullary relapse in 19%. Sixty children reached the second remission. They all were given cytostatic drugs and no ALL children in second remission were transplanted. The estimated probability of overall survival at 10 years from relapse was 16.1% (95% CI: 9.3% - 24%) for all 95 children. 77 children died and most of them were again in relapse. Patients were stratified into 3 subgroups according to time to first relapse: very early (within 18 months from initial diagnosis), early (from 18 to 30 months), and late relapsing children (later than 30 months). The estimated probability of event-free survival at 10 years for these 3 subgroups were 2.2% (95% CI: 0.2%-10%), 12.5% (95% CI: 3.1%-28.7%), and 32.5% (95% CI: 14.6%- 51.9%), respectively (p < 0.0001). Conclusions: The duration of first remission remained the only statistically significant variant to predict the prognosis of relapsed children with ALL.

Nine-Year Survival of Lymphoblastic Lymphoma Patients

This study aimed to analyze the overall survival period of adult lymphoblastic lymphoma patients treated with various therapeutic regimens, and to assess the determinants affecting survival outcome. Twenty-five adult patients with lymphoblastic lymphoma who had been treated at Severance Hospital, Yonsei University College of Medicine, Seoul, Korea from June 1996 to June 2005 were analyzed retrospectively. As an initial remission induction chemotherapy, the hyper-CVAD regimen was performed in eight patients, the Stanford/Northern California Oncology Group (NCOG) regimen in five, the CAVOP regimen in four, the m-BACOP regimen in three, and the CHOP regimen in one patient. Patients were divided into two groups according to their therapeutic modalities. Twenty patients received conventional chemotherapy alone and five received subsequent PBSCT after conventional chemotherapy. Four patients of the PBSCT group underwent autologous PBSCT and one underwent allogeneic PBSCT. The overall response rate was 80% (60% showing a complete response, 20% showing a partial response) and the relapse rate was 73.3%. The overall survival (OS) rate was 55.1% at 1 year, 31.5% at 5 years, and 23.6% at 9 years. The disease-free survival (DFS) rate was 46.7% at 1 year and 30.0% at 7 years. The 5-year OS rate in relation to the regimens was 60% with the Stanford/NCOG regimen, 50% with the CAVOP regimen, and 33.3% with the m-BACOP regimen. The patients treated with the hyper-CVAD regimen had an 18.2% 2-year OS rate, and other patients with CHOP or COPBLAM-V expired early in their course. The OS rate in patients treated with conventional chemotherapy alone was 19.8%, whereas patients treated with subsequent PBSCT after chemotherapy showed 50% overall survival (p=0.25). The age at presentation influenced the outcome of the patients (p=0.01). The Stanford/NCOG regimen is an effective initial choice of therapy for lymphoblastic lymphoma patients, and is superior to the hyper-CVAD regimen in complete response rate and overall survival rate (p=0.36). Addition of PBSCT after chemotherapy may be needed for achieving optimal outcomes.

Isolated testicular relapse in acute lymphoblastic leukemia - effective treatment with the modified CCG-112 protocol.

BACKGROUND: The testes have been considered a sanctuary site for leukemic cells and testicular relapses used to account for a major proportion of the poor outcome of boys with acute lymphoblastic leukemia. With use of aggressive chemotherapy which includes intermediate or high dose methotrexate, the incidence of testicular relapses has declined. However once these patients have received cranial irradiation as a part of the front line protocol, high dose methotrexate needs to be avoided because of risk of developing leucoencephalopathy. AIM: To study the use of non cross resistant chemotherapeutic agents along with a regimen containing lower doses of methotrexate in patients of isolated testicular relapse (ITR). MATERIALS AND METHODS: This is a retrospective analysis of 12 consecutive patients with ITR treated with modified version of the CCG-112 protocol which consists of intensive systemic chemotherapy, cranial chemoprophylaxis along with testicular irradiation. RESULTS: One patient died of regimen related toxicity. Two patients relapsed in the bone marrow during maintenance. Of the nine patients who completed treatment, eight are alive and in remission. One patient had a bone marrow relapse two months after completing treatment. The Kaplan Meier estimates give us an Event Free Survival (EFS) of 66.7% at 10 yrs. CONCLUSIONS: Thus, though the incidence is very low, patients with ITR should be treated aggressively since they have an excellent chance of achieving a long term EFS.

Factores predisponentes para recaída en niños con Leucemia Linfocítica aguada, tratados con el Procologo LLA 2000, en el Hospital Infantil Manuel de Jesús Rivera, Marzo 2000. diciembre 2003 / Factors predisponentes for relapse in children with Leucemia watery ++Linfocítica, treated with ++Procologo ++LLA 2000, in the Infantile Hospital Manuel of Jesus Rivera, March 2000. December 2003

De Marzo 2000 ù Diciembre 2003 en el Servicio de Hemato-Oncología del Hospital Infantil Manuel de Jesús Rivera se diagnosticaron 230 casos de Leucemia Linfocítica Aguda, de éstos 50 presentaron recaídas, se estudiaron 43 pacientes a quienes se les inició tratamiento con el Protocolo LLA 2000. La informaciórt fue recolectada de la Base de datos y Expedientes Clínicos, siendo el estudio descriptivo de corte transversal, retrospectivo.Se encontró que el sexo masculino fue el más afectado, predominando el grupo etéreo de 1 a 5 años, el 23.2 porciento de los pacientes eran originarios de Managua y el 76.8 porciento del resto de los Departamentos del País, el 65.1 porciento de los niños estudiados presentaban algún grado de desnutrición. Al momento del diagnóstico el 79 porciento estaban en condiciones clínicas estables. El sitio de recaída más frecuente fue la médula ósea. El tiempo de recaída más frecuente fue de 7-12 meses. La clasificación inmunológica común o Calla positiva se presentó en el 76.8 porciento de los pacientes. El 65.1 porciento de los pacientes presentó interrupción de la quimioterapia, siendo la causa más frecuente la neutropenia asociada o no a infecciones. En el 42.9 porciento de los pacientes, la interrupcion de quimioterapia duró más de 14 días. El 86 porciento de los pacientes respondió adecuadamente a la monoterapia conPrednisona. Al concluir el estudio la situación de los pacientes fue de remisión el 46.5 porciento; fallecidos 37.2 porciento y nueva recaída 16.3 porciento ...

Incidencia de las leucemias agudas en niños de la ciudad de México, de 1982 a 1991 / Incidence of acute leukemia in children of Mexico city; 1982 to 1991

Objetivo. Medir la tasa de incidencia de las leucemias agudas (LA) en las diferentes delegaciones políticas del Distrito Federal y evaluar si existe una tendencia significativa en dichos padecimientos en tales delegaciones. Material y métodos. Estudio longitudinal descriptivo realizado en seis hospitales de la ciudad de México, los que atienden a cerca de 97.5 por ciento de todos los niños con cáncer de esta ciudad. Los datos se capturaron de 1995 a 1996, y se analizaron en 1999, en el Hospital de Pediatría del Centro Médico Nacional Siglo XXI, del Instituto Mexicano del Seguro Social. Para cada delegación se cal-cularon la tasa de incidencia anual promedio, la tasa es-tandarizada y la razón estandarizada de morbilidad (REM) con intervalos de confianza al 95 por ciento (IC 95 por ciento). La tendencia se evaluó con la tasa de cambio promedio. Re-sultados. Se observó una tendencia al incremento en la incidencia de la leucemia aguda linfoblástica (LAL) en cinco delegaciones: Alvaro Obregón, Cuauhtémoc, Gustavo A. Madero, Izta-calco y Venustiano Carranza. En la leucemia aguda mieloblás-tica (LAM) no se notificaron cambios estadísticamente signi-ficativos en la incidencia en ninguna delegación política. Sólo con LAM se encontró una REM significativa y co-rrespondió a la delegación Alvaro Obregón (REM= 2.91, IC 95 por ciento 1.63 - 4.80). Las REM más altas se encontraron en el sur y suroeste de la ciudad. Conclusiones. Sólo se observó incremento en la incidencia de LAL en cinco delegaciones políticas. La incidencia más alta de LAM se encontró en la delegación Alvaro Obregón.

Resultados a largo plazo de dos protocolos terapéuticos, en niños con leucemia linfoblástica aguda de riesgo habitual. Experiencia en el Centro Médico Nacional "20 de Noviembre" / Long-term results of two therapeutic protocols in children with acute lymphoblastic leukemia of habitual risk. The \"20 of November\" National Medical Center Experience

El objetivo de este trabajo es conocer la sobrevida libre de enfermedad, a largo plazo, en niños con leucemia aguda linfoblástica (LAL), sometidos a dos diferentes programas terapéuticas. Se definió riesgo habitual a pacientes mayores de 2 años y menores de 10, sin infiltraciones neurológica, madiastinal o testicular, con cifra de leucocitos inferior a 25 x 10 a la 9/l y con variedad citomorfológica distinta a L-3. En el primer grupo (LAL81) se incluyeron 30 pacientes, de 1981 a 1986 y recibieron: inducción con vincristina (VCR), y prednisona (PDN); consolidación con mercaptopurina (MP), citarabina (ARA) y doxorubicina (DOX); profilaxis al sistema nervioso central (SNC) con radioterapia y metrotrexate (MTX)-ARA hidrocortisona (HDR) intratecales; sostén con MP y MTX. En el segundo grupo (LAL87) se incluyeron 28 enfermos de 1987 a 1993. Se manejaron: inducción con VCR, PDN y L-asparaginasa (ASP); consolidación temprana y tardía con MP, ARA, DOX, carmustina (BCNU) y ciclofosfamida (CFA); profilaxis al SNC con MTX-ARA-HDR y sostén con MP y MTX. Sólo hubo una falla. Se obsevaron 11 recaídas en el grupo LAL81 y 9 en el otro (p=0.71). De ellas, dos en cada grupo, fueron al SNC. La sobrevida libre de enfermedad en el LAL81 fue de 0.39 a 14 años. En el LAL87 de 0.53 a los 8 años (p=0.62)

Tres casos de necrosis de médula ósea en leucemia aguda / Three cases of bone marrow necrosis in acute leukemia

La necrosis de la médula ósea (NMO) es rara: frecuentemente es un hallazgo post-mórtem que ocurre en pacientes afectados por neoplasias hematológicas, en especial leucemia aguda. Descubrimos aquí NMO en dos pacientes con leucemia aguda mielobástica (LAM) y uno con leucemia aguda linfoblástica (LAL), en quienes se realizó el diagnóstico de NMO en vida. Dos pacientes fallecieron por hemorragia intracraneal; el paciente con diagnóstico de LMA M5 desarrolló NMO una semana después de recibir el segundo ciclo de quimioterapia: su recuperación fue total y está en remisión completa después de casi cinco años del diagnóstico. El diagnóstico de NMO puede ser difícil por lo que se requiere sospecharla para establecer un diagnóstico temprano y brindar tratamiento de apoyo, ya que no necesariamente se asocia a un resultado fatal

Factores pronosticos y mortalidad en pacientes adultos con leucemia aguda e infeccion / Prognostic factors and mortality among adult patients with acute leukemia and infection

Con el objeto de conocer la tasa de mortalidad y los hallazgos clínicos con valor pronóstico en el curso de las infecciones febriles en nuestros enfermos con leucemia aguda estudiamos prospectivamente, durante un lapso de 34 meses, 177 episodios en los que hubo sospecha clínica de infección acaecidos en un grupo de 49 pacientes. Se evaluó mediante análisis univariable y posteriormente por regresión múltiple logística, la asociación de 27 datos clínicos y microbiológicos con la sobrevida en los episodios febriles. La mortalidad global fue elevada (44,9 por ciento) y también la del episodio febril infeccioso (12,7 por ciento). La edad del pacient mayor a 30 años (p = 0,025), la duración de la fiebre durante más de 5 días (p = 0,025), la neumonía (p < 0,001) y la documentación micronbiológica de una infección micótica (p = 0,005) se asociaron con una mayor mortalidad del episodio febril. No obstante, la edad mayor a 30 años (odds ratio ajustado O.R.A. = 1,118; intervalo de confianza del 95 por ciento; IC(95 por ciento) = 1,015 - 1,232; p = 0,025) y la infección pulmonar (O.R.A. = 1,454; I.C.(95 por ciento) = 1,288 - 1,642; p < 0,001) fueron los únicos predictores independientes de mortalidad en el análisis multivariable. Si bien la fiebre de origen desconocido (p = 0,024) se asoció a un mejor pronóstico, sólo la infección viral (O.R.A> = 0,642; I.C.(95 por ciento) = 0,421 - 0,979; p = 0,041) y la producida por más de un tipo de microorganismo (O.R.A. = 0,795; I.C.(95 por ciento) = 0,651 - 0,972; p = 0,027) tuvieron, de acuerdo a la prueba de regresión múltiple logística, un valor protector.

Factores pronósticos en leucemia linfoblástica aguda en niños / Pronostics factors in childrens with acute lymphoblastic leukemia

Los niños con leucemia linfoblástica aguda (LLA) tienen alta probabilidad de alcanzar una prolongada sobrevida total y eventual curacion cuando son tratados con una terapia ajustada a los factores pronósticos . Este trabajo analiza una cohorte no recurrente del Hospital Universitario de Caracas (HUC) desde 1980 a 1985, de 55 historias de pacientes con diagnóstico de LLA, comprendidos entre 6 meses y 18 años de edad, tratados con el "Protocolo Nacional 80". Este trabajo tuvo como objetivo básico, establecer si hubo una probabilidad de sobrevida total mayor de dos años, en pacientes con factores de buen pronóstico tratados con el P.N.80, en comparacion con los de mal pronóstico

Causes of mortality in children with acute lymphocytic leukemia.

Fifty five deaths between January, 1982 to September, 1989 in children with acute lymphoblastic leukemia (ALL) were evaluated to determine the cause of mortality. Fifty cases died during remission. Infection alone was responsible for death in 26 of 55 (47.3%) cases while hemorrhage was seen in 7 (12.7%) children. Infection and hemorrhage together were responsible in another 13 cases. Gastrointestinal tract and pulmonary system were the major sites of bleeding. Infections either alone or in combination with other factors were responsible for death in 42 of 55 (76.5%) of children. Septicemia (n = 11), gastrointestinal (n = 15) and pulmonary infections (n = 10) and meningitis in 2 cases were the major sites of infections. Pseudomonas and Klebsiella in 6 cases each accounted for 54.5% of isolates.

Therapeutic results and prognostic predictors of childhood acute lymphoblastic leukemia: Cox regression analysis

Determining the current status of therapeutic results of acute lymphoblastic leukemia (ALL), and identifying the important clinical predictors of survival and relapse are essential for establishing therapeutic strategies. Sixty-two children with ALL who were admitted to Chonnam University Hospital from January 1983 to June 1991 were studied. With a mean follow-up period of 53.7 months, the overall 5-year survival rate (5YSR) was 46.1%. The overall rate of 5-year event-free survival (EFS) was 25.4% and significantly differed between risk groups: 48.7% for standard, 16.3% for high, and 12.5% for very high (p<.05). Overall 4-year survival after initial relapse was 34.2% and there was no significant difference in survival between those who relapsed during maintenance therapy and those who relapsed after completing maintenance. The Cox proportional hazards model identified central nervous system (CNS) irradiation (P<0.001) as having the most important influence upon EFS, followed by serum alanine aminotransferase level, platelet level, and age. On the other hand, CNS leukemia at diagnosis, followed by mediastinal mass, and hemoglobin level were found to be the most important prognostic predictors for relapse. On the basis that present results differ from those of developed countries, we suggest the necessity of a nation-wide cohort study to delineate the characteristics of Korean ALL in children, to make our own protocols, and ultimately to improve the therapeutic outcome.