General AML

Feasibility of MRD detection by multiparametric flow cytometry for AML in Brazil

Minimal Residual Disease (MRD) is a significant prognostic factor for survival and relapse in Acute Myeloid Leukemia (AML). In developing countries such as Brazil, performing MRD assessment in patients with AML is quite uncommon due to cost and lack of infrastructure. Lorena Lobo de Figueiredo-Pontes from the Medical School of Ribeirão Preto, São Paulo, Brazil, and colleagues were “particularly interested in implementing a standardized multicenter protocol for MRD evaluation to further assess treatment outcomes of AML in a large and developing country like Brazil.”

To do this, Figueiredo-Pontes et al., investigated in a multicenter study, the feasibility of a MRD protocol for low- or intermediate risk Acute Myeloid Leukemia (AML) patients treated with standard chemotherapy with or without Autologous Stem Cell Transplantation (auto-HSCT) as part of a current Brazilian feasibility study ran by the International Consortium of Acute Leukemia (ICAL) . The results of the study were reported in the December 2017 issue of Blood Advances.

Overall, 84 AML patients between the age of 18 – 65 years were enrolled in this study. Diagnostic samples were analyzed by a Brazilian team trained at the Yong Loo Lin School of Medicine, Singapore. The samples were analyzed using the following variables: period of time from collection to acquisition with flow cytometry, quality of the sample based on Multi-Parametric Flow Cytometry (MPFC) quality control standard criteria, and number of cases with Leukemia-Associated Aberrant Immunophenotypes (LAIPs [distinct aberrant immunophenotype on AML blasts]) suitable for MRD detection with a sensitivity of ≥ 0.1%. Diagnostic bone marrow samples suitable for MRD assessment were available for 70 patients. MRD was assessed at the time of diagnosis, after each course of chemotherapy (MRD1 and MRD2), pre- and post- allo-HSCT (MRD3 and MRD4) and then once every three months for two years (MRD5–12).

The authors highlighted that following this method employed in this study, LAIPs suitable for MRD detection with a sensitivity of at least 0.1% was identified for all patients. The most frequent LAIPs used for MRD detection include CD45dim/CD34/CD117/CD33/CD38/HLA-DR (n = 55), CD45dim/CD34/CD117/CD33/CD11c/CD64 (n = 40) and CD45dim/CD34/CD117/CD33/CD19/CD13 (n = 41). They also noted that as of July 2017, 46.4%, 28.5%, 10.7% and 6% of the included samples have already been analyzed at MRD1, MRD2, MRD3 and MRD4 time points, respectively.

According to the authors, these results confirm the “feasibility of the development of MRD studies in a relatively large developing country” such as Brazil. They further noted that the training of personnel and establishment of the network with a minimal infrastructure have enabled the identification of LAIPs suitable for MRD detection.  Figueiredo-Pontes et al. proposed that the recommended MRD detection procedure should be validated in everyday clinical routine which could possibly lead to an implantation of a uniform protocol that may improve inter-laboratory standardization in Brazil.

References
  1. Figueiredo-Pontes L.L.et al. Feasibility of minimal residual disease studies by multiparametric flow cytometry for acute myeloid leukemia in a developing country. Blood Advances. 2017 Dec 8. DOI: 10.1182/bloodadvances.2017GS102444 [Epub ahead of print]
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