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ABSTRACT Introduction: Improving survival of Acute Lymphoblastic Leukemia (ALL) in adult patients has been a challenge. Despite intensive chemotherapy treatment, overall survival is poor. However, several studies demonstrate that young adult patients have better survival when treated with pediatric-based intensive regimens. Considering these results, We decided to treat newly diagnosed ALL patients according to age and risk factors. The goal of this study was to describe the results of this intensive chemotherapy treatment approach for ALL adult patients diagnosed at our institution. Methods: Fifty-eight ALL patients, diagnosed from 2004 to 2013, were included in the analysis. Patients were assigned to either the St. Jude Total Therapy XIIIB high-risk arm (St Jude) or the CALGB 8811 (CALGB). The Kaplan-Meier survival curve was used for the survival analyses and the Cox proportional hazard regression, for multivariable analysis. Results: The overall survival was 22.9% at 10 years. The St. Jude improved survival, compared to the CALGB (p = 0.007), with 32.6% vs. 7.4% survival rate at 10 years. However, no survival benefit was found for patients younger than 20 years old (p = 0.32). The multivariable analysis demonstrated that undetectable minimal residual disease (MRD) and hematopoietic stem cell transplantation (HSCT) had beneficial impact on survival (p = 0.0007 and p = 0.004, respectively). Conclusion: ALL is a disease of poor prognosis for adults. The joint effort to standardize treatment and seek solutions is the way to start improving this scenario.
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ABSTRACT Introduction: Acute promyelocytic leukemia (APL) is caused by t(15;17)(q24;q21) translocation, which product is the fusion oncoprotein PML-RARa (promyelocytic leukemia-retinoic acid receptor alpha). The morphology of leukemic promyelocytes is usually characteristic, with the presence of faggot cells and coarse cytoplasmic granulations; immunophenotype is characteristic in most cases. However, definitive laboratory diagnosis should be performed by detecting t(15;17) or by PML-RARa fusion protein. Objectives: To compare cytomorphology, flow cytometry, and classical cytogenetic of bone marrow samples from patients with APL, treated at the Complexo Hospital de Clínicas da Universidade Federal do Paraná (CHC-UFPR), as well as describe the possible discrepancies between the methodologies. Method: Retrospective analysis of APL cases treated at the CHC-UFPR from January 2000 to July 2018. Results: Eighty-eight patients (42 man/ 46 woman; mean age: 34 years), 42.1% of them presented a high-risk prognosis. Flow cytometry was performed in 83 cases (94.3%); karyotype was performed in 79 cases (89.7%), but translocation t(15;17) was confirmed in only 53 cases (60.2%). From the 28 patients with a non-conclusive karyotype; fourteen (15.9%) of them presented the PML-RARa transcript in the molecular analysis. In total, 35 patients (39 8%) performed research of the PML-RARa gene by molecular biology. Only 45 patients (51.1%) presented concordant diagnosis among the three technical exams (morphology, flow cytometry and cytogenetics). Overall survival was 67% at 4.8 years, with 29 deaths. Conclusion: Genetic confirmation was observed in 76.1% of samples, 60.2% by conventional cytogenetics and 15.9% by molecular biology. There was a disagreement between the methodologies, and a low sensibility of the conventional cytogenetics, demonstrating the importance of performing molecular techniques for diagnostic confirmation.
RESUMEN Introducción: La leucemia promielocítica aguda (LPA) es causada por la translocación t(15;17)(q24;q21), cuyo producto es la oncoproteína de fusión PML-RARa (proteína de la leucemia promielocítica-receptor alfa de ácido retinoico). La morfología de los promielocitos leucémicos suele ser típica, con presencia de células faggot (células en haces) y gruesasgranulaciones citoplásmicas; el inmunofenotipo es característico en la mayor parte de los casos. No obstante, el diagnóstico final de laboratorio debe ser hecho por la detección de la t(15;17) o por la oncoproteína PML-RARa. Objetivos: Comparar la citomorfología, la citometría de flujo y la citogenética clásica de muestras de médula ósea de pacientes con LPA asistidos en el Complexo Hospital de Clínicas da Universidade Federal do Paraná (CHC-UFPR), así como describir lasposibles discrepancias entre los métodos. Método: Análisis retrospectivo de los casos de LPA asistidos en el CHC-UFPR entre enero de 2000 y julio de 2018. Resultados: De los 88 pacientes (42 hombres y 46 mujeres; edad promedio: 34 anos), 42,1% presentaron pronóstico de alto riesgo. Citometría de flujo se realizó en 83 casos (94,3%); cariotipo en 79 casos (89,7%),pero la translocación se confirmó en sólo53 (60,2%) casos. Entre los28 pacientes con cariotipo no concluyente, 14 (15,9%) presentaron el transcripto PML-RARa. En total, 35 pacientes (39,8%) realizaron la pesquisa del gen PML-RARa por biología molecular. Cuarenta y cinco pacientes (51,1%) tuvieron diagnóstico acorde entre los métodos (morfología, citometría de flujo y citogenética). La supervivencia global fue de 67% en 4,8 anos, con 29 muertes. Conclusión: Hubo confirmación genética en 76,1% de las muestras, siendo 60,2% por citogenética y 15,9%por biología celular. Hubo desacuerdo entre los métodos y baja sensibilidad de la citogenética convencional, lo que demuestra la importancia de la realización de técnicas moleculares para confirmación diagnóstica.
RESUMO Introdução: A leucemia promielocítica aguda (LPA) écausada pela translocação t(15;17)(q24;q21), cujo produto éa oncoproteína de fusão PML-RARa (leucemia promielocítica-receptor alfa do ácido retinoico). A morfologia dos promielócitos leucêmicos é habitualmente característica, com presença de faggot cells (células em maços ou feixes) e granulações citoplasmáticas grosseiras; o imunofenótipo é característico na maioria dos casos. Porém, o diagnóstico laboratorial definitivo deve ser feito pela detecção da t(15;17) ou pela oncoproteína PML-RARa. Objetivos: Comparar a citomorfologia, a citometria de fluxo e a citogenética clássica de amostras de medula óssea de pacientes com LPA atendidos no Complexo Hospital de Clínicas da Universidade Federal do Paraná (CHC-UFPR), bem como descrever as possíveis discrepâncias entre as metodologias. Método: Análise retrospectiva dos casos de LPA atendidos no CHC-UFPR entre janeiro de 2000 e julho de 2018. Resultados: Dos 88 pacientes (42 homens e 46 mulheres; média de idade: 34 anos), 42,1% apresentaram prognóstico de alto risco. A citometria de fluxo foi realizada em 83 casos (94,3%); o cariótipo, em 79 casos (89,7%), mas a translocação foi confirmada em apenas 53 (60,2%) casos. Dos 28 pacientes com cariótipo não conclusivo, 14 (15,9%) tinham a presença do transcrito PML-RARa. No total, 35 pacientes (39,8%) realizaram a pesquisa do gene PML-RARa por biologia molecular. Quarenta e cinco pacientes (51,1%) obtiveram diagnóstico concordante entre as metodologias (morfologia, citometria de fluxo e citogenética). A sobrevida global foi de 67% em 4,8 anos;com 29 óbitos. Conclusão: A confirmação genética foi realizada em 76,1% das amostras, sendo 60,2%por citogenética e 15,9% por biologia molecular. Houve discordância entre as metodologias e baixa sensibilidade da citogenética convencional, o que demonstra a importância da realização de técnicas moleculares para confirmação diagnóstica.