Molecular and hematologic relapses in adult patients with acute promyelocytic leukemia: a cohort study

Abstract Objective: To evaluate factors predictive for relapse in a cohort of adult patients with acute promyelocytic leukemia monitored by molecular methods during consolidation and during at least one month of maintenance therapy. Methods: The charts and laboratory data of 65 adult patients with acute promyelocytic leukemia treated according to the International Consortium on Acute Promyelocytic Leukemia 2006 protocol were reviewed. The identification of the promyelocytic leukemia-retinoic acid receptor-alpha gene rearrangement at diagnosis, post-induction, post-consolidation and during maintenance treatment was performed by qualitative and quantitative reverse transcription polymerase chain reaction. Results: Eighty-nine patients were diagnosed with acute promyelocytic leukemia over a seven-year period and of these 65 were eligible for treatment with the protocol. Among the 45 patients who received consolidation and maintenance treatment, six (13%) relapsed, three of whom presented hematologic and three presented molecular relapse. The first relapses occurred at a median of 39 months. Relapsed patients were from all risk groups (low, intermediate and high) and both morphological types (M3 and M3variant) were found. Three of these patients are alive and in molecular remission after salvage treatment. There were no statistically significant differences regarding gender, age, risk group, morphology, promyelocytic leukemia breakpoint cluster region, use of all-trans retinoic acid, development of differentiation syndrome and number of days to complete remission between the patients who relapsed and those who did not. Conclusion: Our results reinforce the importance of prolonged monitoring of acute promyelocytic leukemia patients using molecular methods to detect relapse early.

Hyperglycemia increases the complicated infection and mortality rates during induction therapy in adult acute leukemia patients

OBJECTIVE: To determine the prevalence of hyperglycemia during induction therapy in adult patients with acute leukemia and its effect on complicated infections and mortality during the first 30 days of treatment. METHODS: An analysis was performed in a retrospective cohort of 280 adult patients aged 18 to 60 years with previously untreated acute leukemia who received induction chemotherapy from January 2000 to December 2009 at the Hemocentro de Pernambuco (HEMOPE), Brazil. Hyperglycemia was defined as the finding of at least one fasting glucose measurement > 100 mg/dL observed one week prior to induction therapy until 30 days after. The association between hyperglycemia and complicated infections, mortality and complete remission was evaluated using the Chi-square or Fisher's exact tests by the Statistical Package for Social Sciences (SPSS) in the R software package version 2.9.0. RESULTS: One hundred and eighty-eight patients (67.1%) presented hyperglycemia at some moment during induction therapy. Eighty-two patients (29.3%) developed complicated infections. Infection-related mortality during the neutropenia period was 20.7% (58 patients). Mortality from other causes during the first 30 days after induction was 2.8%. Hyperglycemia increased the risk of complicated infections (OR 3.97; 95% confidence interval: 2.08 - 7.57; p-value < 0.001) and death (OR 3.55; 95% confidence interval: 1.77-7.12; p-value < 0.001) but did not increase the risk of fungal infections or decrease the probability of achieving complete remission. CONCLUSION: This study demonstrates an association between the presence of hyperglycemia and the development of complicated infections and death in adult patients during induction therapy for acute leukemia.

Fatores prognósticos em crianças e adolescentes com Leucemia Linfóide Aguda / Prognostic factors in children and adolescents with Acute Lymphoblastic Leukemia

OBJETIVOS: descrever características clínico-laboratoriais, determinar taxas de resposta ao tratamento e identificar fatores de risco que influenciaram na sobrevida de pacientes pediátricos com leucemia linfóide aguda (LLA). MÉTODOS: estudo retrospectivo do tipo série de casos com 108 pacientes de idade até 18 anos, admitidos para tratamento de LLA na Fundação de Hematologia e Hemoterapia de Pernambuco (HEMOPE), Brasil, de janeiro de 1993 a dezembro de 2001. As variáveis analisadas foram: sexo, idade, principais sintomas e sinais, leucometria, imunofenótipo e grupo de risco ao diagnóstico, taxas de remissão e recaída, óbito e sobrevida global, local de recaída e fatores de risco para a sobrevida. Medidas descritivas foram usadas para a análise estatística. O tempo de sobrevida dos pacientes foi estimado através da função de sobrevida de Kaplan-Meier e Log-Rank. O efeito de fatores de risco no tempo de sobrevida foi avaliado através do Modelo de Regressão de Cox. RESULTADOS: foi encontrada a relação masculino:feminino de 1,7:1, mediana de idade ao diagnóstico de oito anos, freqüência de queixas músculo-esqueléticas (51 por cento), infiltração do sistema nervoso central (8 por cento), LLA-Precursor B (81 por cento) e LLA-T (19 por cento). A distribuição dos grupos correspondeu a Risco Básico Verdadeiro (12 por cento), Risco Básico (21 por cento) e Alto Risco (67 por cento). As principais taxas foram: remissão (86 por cento), óbitos na indução (5,5 por cento), recaída (24 por cento) e sobrevida global (62,5 por cento). CONCLUSÕES: a variável de impacto na sobrevida foi a leucometria. A taxa de sobrevida global foi influenciada pela freqüência elevada de pacientes considerados de alto risco.

OBJETIVES: to describe the clinical and laboratory characteristics, determine rates of response to treatment and pinpoint risk factors that influence the survival of pediatric patients with acute lymphoblastic leukemia (ALL). METHODS: this is a retrospective series of case studies involving 108 patients aged 18 years or under hospitalized for ALL treatment at the Fundação de Hematologia e Hemoterapia de Pernambuco (HEMOPE), Brazil, between January 1993 and December 2001. The following variables were analyzed: gender, age, main symptoms and signs, white blood-cell count, immunophenotype and risk group on diagnosis; rates of remission and relapse, death and overall survival; place of relapse and risk factors for survival. Descriptive measurements were used for the statistical analysis. The patient survival time was estimated using the Kaplan-Meier survival function and Log Rank. The effect of risk factors on survival time was evaluated using the Cox Regression Model. RESULTS: the results showed a male:female ratio of 1.7:1, a median age of eight years on diagnosis, the frequency of musculoskeletal complaints was 51 percent, of infiltration of the central nervous system 8 percent, of ALL-Precursor B 81 percent and ALL-T 19 percent. The distribution of the groups corresponded to True Basic Risk (12 percent), Basic Risk (21 percent) and High Risk (67 percent). The rates of remission, relapse and overall survival were 86 percent, 24 percent and 62.5 percent, respectively. CONCLUSIONS: the variable having an impact on overall survival was the white blood-cell count. The overall survival rate in the study was influenced by the high frequency of high-risk patients.