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Editorials
Although the retrospective nature of the study and the heterogeneity of the treatments administered prevent the authors from assessing OS in this series, these data identify important differences between the two main CLL immuno- genetic subgroups and may help in building a novel CLL patient risk stratification where BCR plays a major role as the core of the prognostic model. For example, trisomy 12, associated to an intermediate prognosis in CLL analyzed as a whole, now has a better definition, having a detrimental prognostic impact on TTFT within M-CLL but not within U-CLL. Moreover, subset #2 should be identified and reported since it has an independent impact on TTFT with- in M-CLL.
The CLL prognostic algorithms proposed so far have always included IGHV status. However, in six different scoring systems (CLL-IPI, MDACC 2007, MDACC 2011, GCLLSG, Barcelona-Brno, O-CLL1), the outcome predic- tion fails in a proportion ranging from 22% to 35% of early phase CLL.20 Especially within low-risk CLL, there is still a sizable proportion of patients experiencing “early” progres- sion. A prognostic algorithm built within the U-CLL and M- CLL IGHV categories may overcome this limitation. This has clinical implications for patients’ counseling, follow-up planning, and potential enrollment in trials exploring early treatment approaches for stage A CLL.
It is clear that, in an era of new drugs, the value of all the algorithms proposed so far in terms of prediction of OS will need to be re-evaluated, since the BCR/BCL2 inhibitors have the power to overcome the prognostic impact of the IGHV mutational status. For the time being, besides TP53 deletions/mutations, it is advisable to consider IGHV gene sequencing in all CLL patients requiring first-line treatment as a guide to choose between conventional and innovative approaches. In this respect, the ERIC initiative on the IGHV and TP53 harmonization project and the certification sys- tem, with external quality controls for the accreditation of the laboratories performing IGHV/TP53 analysis, is a very timely effort.
Acknowledgments
The authors wish to thank Associazione Italiana per la Ricerca sul Cancro (AIRC) 5 x 1000, Milan, Italy (Special Program Molecular Clinical Oncology MCO-10007; Metastases Special Program, n. 21198). They thank Dr. Sara Raponi and Dr. Luca Vincenzo Cappelli for their contribution in the design of Figure 1.
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