Immunophenotypic changes in juvenile myelomonocytic leukaemia after treatment with hypomethylating agent: Do they help to evaluate dept of response?

5-Azacitidine has been used before stem cell transplantation in juvenile myelomonocytic leukaemia (JMML) patients. Recently, we have described immunophenotypic features in JMML at diagnosis. Here, our aim was to examine the changes in the immunophenotypic features during azacitidine treatment, correlating it with clinical response. Patients treated with 5-azacitidine were evaluated at diagnosis and after three and six cycles of medication. Among 32 patients entering the study, 28 patients were examined after three cycles and 25 patients after six. Patients showed a reduction in CD34/CD117+ cells: median 3.35% at diagnosis, 2.8% after three cycles and 1.63% after six. B-cell progenitors were decreased at diagnosis and decreased after treatment. Monocytes decreased: 11.91% to 6.4% and 4.18% respectively. Complete response was associated with increase in classical monocytes. T lymphocytes, reduced at diagnosis, increased in patients responding to 5-azacitidine. Immunophenotypic aberrancies including expression of CD7 in myeloid progenitors remained after treatment. This feature was associated with a worse response to treatment, as well as presence of NF1. Immunophenotyping was feasible in all patients. Clinical response was associated with a decrease of myeloid progenitors and monocytes and a rise in T lymphocytes although phenotypic aberrancies persisted. The largest effect was observed after three cycles.

Immunophenotypic characteristics of juvenile myelomonocytic leukaemia and their relation with the molecular subgroups of the disease.

The diagnosis of juvenile myelomonocytic leukaemia (JMML) is based on clinical, laboratory and molecular features but immunophenotyping [multiparametric flow cytometry (MFC)] has not been used routinely. In the present study, we describe the flow cytometric features at diagnosis with special attention to the distribution of monocytic subsets and the relation between MFC and molecular subgroups. MFC was performed with an eight-colour platform based on Euroflow. We studied 33 JMML cases. CD34+ /CD117+ /CD13+ cells >2% was found in 25 cases, and 51·5% presented an aberrant expression of CD7. A decrease of CD34+ /CD19+ /CD10+ cells was seen in eight cases and in four they were absent. The granulocytic population had a decreased side scatter in 29 cases. Bone marrow monocytic precursors were increased in 28 patients, with a decrease in classical monocytes (median 80·7%) and increase in CD16+ (intermediate and non-classical). A more pronounced increase in myeloid CD34+ cells was seen in patients with Neurofibromatosis type 1 (NF1) and tyrosine-protein phosphatase non-receptor type 11 (PTPN11), with aberrant CD7 expression in four of six and 10/12 patients respectively. Thus, JMML shows an immunophenotypic profile similar to myelodysplastic syndromes, and a different monocyte subset distribution when compared with chronic MML. MFC proved to be an important diagnostic tool that can help in differential diagnosis with other clonal diseases with monocytosis.

Tradução, Adaptação Cultural e Validação do Questionário “Reação Médica à Incerteza (PRU)” na Tomada de Decisões / Translation, Cultural Adaptation and Validation of the “Physicians’ Reactions to Uncertainty (PRU)” Questionnaire

Introdução A incerteza influencia diretamente a tomada de decisões pelos médicos, e a inabilidade em lidar com ela pode resultar em cuidados médicos com baixo padrão de qualidade eem desperdício de recursos em saúde. A incerteza também afeta a satisfação profissional e a qualidade de vida desses profissionais. O questionário Physicians’ Reactions to Uncertainty (PRU) objetiva quantificar as reações afetivas de médicos à incerteza e suas maneiras de lidar com ela. Os objetivos deste trabalho são a tradução para o português, a adaptação cultural e a validação do questionário PRU. Materiais e métodos Estudo transversal analítico, que compreende a tradução, retrotradução e adaptação cultural do questionário PRU. As etapas posteriores consistiram em validação na população-alvo, seguida de avaliação de reprodutibilidade intra e interobservador, e análise da consistência interna. Na avaliação da consistência interna do instrumento foi utilizado o coeficiente alfa de Cronbach; e na análise da reprodutibilidade intra e interobservador, o coeficiente de correlação de Pearson. Resultados Em todos os domínios do questionário, os resultados da correlação intraobservador (test-retest) e interobservador (concordância total) pelo testede correlação de Pearson foram estatisticamente significantes, com p<0,01. De forma geral, a consistência interna do instrumento foi moderada, com um alfa de Cronbach de 0,58. Entre as várias dimensões, atingiu-se consistência moderada, com valores que oscilaram ao redor de 0,6. Conclusões A versão brasileira do questionário PRU tem propriedades de medida adequadas e oferece um novo instrumento nesse campo de pesquisa, possibilitando melhor compreensão da incerteza gerada na tomada de decisão clínica. .

Introduction Uncertainty directly influences physicians’ decision-making, and their inability to deal with it can result in substandard medical care and wasted health care resources. Uncertainty also affects the job satisfaction and quality of life of such professionals. The Physicians’ Reactions to Uncertainty (PRU) questionnaire aims to quantify the emotive reactions of physicians to uncertainty and their ways of dealing with it. The objectives of this study are the Portuguese translation, cultural adaptation and validation of the PRU questionnaire. Materials and Methods Cross-sectional analytic study involving translation, back-translation and cultural adaptation of the PRU questionnaire. The subsequent steps consisted of validation in the target population, followed by assessment of intra- and inter-observer reproducibility and internal consistency analysis. Cronbach’s alpha was used to evaluate the internal consistency of the questionnaire, and Pearson’s Correlation Coefficient was applied for the test-retest. Results In all areas of the questionnaire the results of the intra-observer (test-retest) and inter-observer (total agreement) correlation through Pearson’s correlation test were statistically significant, with p < 0.01. Overall, the internal consistency of the questionnaire was moderate, with a Cronbach’s alpha score of 0.58. Among the various dimensions, a moderate consistency was achieved, with values oscillating around 0.06. Conclusions The Brazilian version of the PRU questionnaire has demonstrated adequate measurement properties and offers a new instrument in this field of research, enabling better understanding of the uncertainty generated in clinical decision-making. .