Analysis of percent identity of IGHV mutation as prognostic factor in CLL patients treated with fludarabine, cyclofosfamide and rituximab: a single centre experience

ackground:The mutation status of the immunoglobulin heavy chain vari-able region gene (IGHV) is an established prognostic factor in patients withchronic lymphocytic leukaemia (CLL). The degree of somatic hypermuta-tion, determined as percent sequence identity to germline in IGHV(IGHV%) is analyzed in clinical practice. Currently CLL with<98% IGVHidentity are considered “mutated” and CLL patients with >98% IGHVidentity are considered “unmutated. ” Recent data have assessed the prog-nostic role of IGHV% as a continuous variable in CLL patients treatedwith fludarabine, cyclophosphamide and rituximab (FCR).Aims:In our study we investigated the prognostic significance of absolutepercent identity of somatic of IGHV mutation on Progression Free Survival(PFS) and Overall Survival (OS) in unmutated CLL patients (pts) treatedwith frontline FCR in our Institution.Methods:We retrospectively evaluated 73 pts with CLL treated with front-line FCR at the University Hospital of Bari (Italy) with a median of 5 years ollow-up. The mutational status of the IGHV was studied in all pts andthe degree of somatic hypermutation of IGHV was determined as percentidentity from the germline sequence. Pts were divided in mutated and unmu-tated using a cut-off of 98% sequence identity. Among unmutated pts (iden-tity sequence >98%) we selected two groups: the first one between 98%and 99% (IGHV-98-99%) and the second one with identity range between99% and 100% (IGHV-99-100%), respectively. PFS and OS were calculateand compared between the two groups.Results:Among the 73 CLL pts treated with frontline FCR 48 pts (65%)with unmutated IGHV CLL were identified; among them, 20 pts (41%)and 28 (59%) belonged to IGHV 98-99% and IGHV 99-100% group,respectively. No significant differences were observed (p=ns) in terms ofPFS and OS between the two groups.Summary/Conclusion:In our study no difference in terms of survival wasobserved in unmutated IGHV CLL pts on the basis of the percent identityof IGHV mutation for distinguishing two classes of risk. Further studiesand more consistent cohorts of pts are warranted to confirm these data.