IMPACT OF CLINICAL AND CYTOGENETIC-MOLECULAR FACTORS ON SURVIVAL OF ADOLESCENTS AND YOUNG ADULTS WITH ACUTE LYMPHOBLASTIC LEUKAEMIA

Vol 1, 2020 - 131311
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Abstract

Introduction and Objectives: Acute lymphoblastic leukaemia (ALL) has a worse prognosis in adults, associated with specific genetic profiles. In addition to the higher frequency of high-risk cytogenetics, 40-50% of adults harbour IKZF1 deletions, those alterations are negative prognostic markers in children. Patients aged 15-39 years-old, named Adolescents and Young Adults (AYA), have markedly worse results than younger counterparts. Besides biology disparities, therapeutic strategies contribute to these poor outcomes. In this study, we aim to characterize a consecutive series of ALL cases from a reference institution for the treatment of haematological diseases and evaluate the overall (OS) and event-free (EFS) survivals of these patients according to the age group, type of therapeutic protocol and cytogenetic–molecular characteristics (including IKZF1 deletions). Material and Method: Patients aged ≥15 years-old diagnosed with ALL, treated at HEMORIO between 2012-2020 were included. The patients’ follow-up data are currently being collected to enable the survival analyses to be carried out. Cytogenetic-molecular characterization is routinely performed by karyotyping, RT–PCR and FISH. IKZF1 status is being determined using MLPA and multiplex PCR. The OS and EFS will be determinate using the Kaplan-Meier method from the date of diagnosis until outcome (death, alive or last follow-up).
Variables known to be associated with prognosis, such as age, WBC count and genetic profiles will be evaluated and differences between survival distributions will be compared by the log-rank test. Results and Conclusion: To date, we included 97 patients, 47 women and 50 men with the majority aged 15-39 years-old (56.7%, AYA group). There was a predominance of B cell precursor (B-ALL) subtype (n=77) in comparison to T-cell (T-ALL) (n=20). The AYA group accounted for 70% of the T-ALL cases. Of the 50 B-ALL cases with available immunophenotypic subclassification, 4 were pro-B, 10 pre-B and 34 B-common. For the T-ALL patients, 3 were categorised as early T-cell precursor, 2 medullary and 4 cortical subtypes. Twenty-eight B-ALL patients (> 50x109/L) and 8 with T-ALL (> 100x109/L) presented high WBC. Cytogenetic-molecular analyses were performed in 68 patients, with 47% being BCR-ABL1, 3% KMT2A-r and 4 TCF3-PBX1. IKZF1 deletions were identified in 19.5% (19/97) of the cases, 13 of them evolved to death (4 due to disease relapse). Our preliminary data showed that 74% of the patients have died, with sepsis being the main cause of death (49%), followed by disease recurrence/progression (16%). The main protocols used were BFM (n=40) and HyperCVAD (n=39). The OS and EFS analyses are in progress. Even though we are aware that most of our cases are in the AYA group and that the adoption of paediatric protocols to treat these patients might result in an improved outcome, so far we were unable to observe this benefit, because the majority of our patients died due to sepsis.

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Author

Thais Aguiar

Obrigada elas perguntas Isabela , Em relação a prevalência de IKZFZ, cerca de 40-50% dos adultos com LLA podem apresentar a deleção, sendo percentual ainda maior em pacientes Ph+. Nosso percentual foi abaixo do descrito porém não conseguimos realizar análise em todos os casos por baixa qualidade ou falta de material.Se olharmos somente para os casos em que conseguimos realizar a análise com precisão, teremos percentual semelhante ao da literatura. Sobre as estratégias terapêuticas nos adolescentes e adultos jovens, estudos evidenciam benefício no uso de protocolos pediátricos, que se baseam na intensificação  de drogas não mieloablativas( corticóide, vincristina, asparaginase), maior utilização de agentes antimetabólitos( MTX, tiopurinas), menor utilização de antracíclicos e na intensificação de profilaxia de sistema nervoso central. Uma limitação entretanto é que apesar de mais eficazes são também protocolos mais complexos, o que exige maior experiência da equipe, principalmente em relação a manejo das toxicidades. São ainda protocolos mais longos, demandando maior adesão do paciente, condição sabidamente menor no grupo dos adolescentes e adultos jovens. Sobre os dados de mortalidade, se comparamos com estudos na América Latina observamos que Sepse também segue como principal causa de óbito, com taxas muito superiores às demonstradas em estudos realizados em países de primeiro mundo. Entretanto temos poucos estudos caracterizando  toda a população tratada. Maioria descreve resultados de protocolos específicos utilizados em uma parcela da população. Após nossa análise inicial temos buscado, com auxílio da direção do hospital, melhorias em estrutura física, como redução de número de leitos por enfermaria e estratégias de uso de profilaxia antibiótica durante neutropenia.

Isabella Guimarães

Muito obrigada pelas respostas! Boa sorte no projeto e novamente parabéns!
Author

Thais Aguiar

Boa tarde ,  Os elevados índices de óbito por Sepse parecem estar relacionados a condição socioeconômica dos pacientes, com suporte domiciliar inadequado, dificil acesso ao hospital , bem como suporte hospitalar limitado e alto índice de infecções por germes multi resistentes .  
Institutions
  • 1 Instituto Estadual de Hematologia
  • 2 Division of Clinical Research, Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA), Rio de Janeiro, Brazil
  • 3 Pesquisa clínica / Instituto Nacional do Câncer / Divisão de Pesquisa
  • 4 INSTITUTO NACIONAL DO CANCER
  • 5 Research Centre, Instituto Nacional de Câncer - INCA / INCA
  • 6 Pesquisa Clínica / INSTITUTO NACIONAL DE CANCER / Instituto Nacional de Câncer
Keywords
Acute lymphoblastic leukaemia
adolescents and young adults