Standardization of molecular monitoring for chronic myeloid leukemia in Latin America using locally produced secondary cellular calibrators

RUIZ MS; MEDINA M; TAPIA I; MORDOH J; CROSS NCP; LARRIPA I; BIANCHINI M

LEUKEMIA

NATURE PUBLISHING GROUP

Año: 2016 vol. 30 p. 2258 - 2260

0887-6924

Residual disease in chronic myeloid leukemia (CML) patients undergoing therapy with tyrosine kinase inhibitors (TKIs) is measured by assessing the quantity of transcripts of the BCR-ABL1 fusion gene in peripheral white blood cells. This analysis is based on reverse-transcription quantitative PCR technology; however, the wide array of methods used worldwide has led to large variation in quantitative BCR-ABL1 measurements, which hamper inter-laboratory comparative studies. It is now recognized that monitoring BCR-ABL1/control gene ratios on the International Scale is vital for the management of patients with CML. Efforts to harmonize procedures to measure BCR-ABL1 fusion transcripts have included important investments in sample exchange programs to derive laboratory-specific conversion factors; these efforts showed improvements in inter-laboratory concordance rates, but the process is laborious and limited due to the lack of a common set of reference samples that can be shared on a global scale. This requirement was recently addressed in part by the formulation and validation of the first World Health Organization (WHO) International Genetic Reference Panel for quantitation of BCR-ABL1 by RT-qPCR. The WHO primary standards consist of a 4-level panel of e14a2-positive lyophilized cell line dilutions. Each level has an assigned IS-value, which was obtained by repeated testing of each sample level in expert IS-standardized laboratories. Unfortunately, the stock of WHO primary standards is limited, and their accessibility has been restricted to manufacturers of testing kits or secondary reference standards. In this study, we aimed to develop and validate secondary reference materials calibrated to the IS through the WHO primary standards in order to facilitate standardization of molecular monitoring in Latin America.