Journal
BRITISH JOURNAL OF HAEMATOLOGY
Volume 180, Issue 1, Pages 33-40Publisher
WILEY
DOI: 10.1111/bjh.15018
Keywords
CLL; FCR; IGHV gene; immunoglobulin heavy chain gene
Categories
Funding
- NIH/NCI [P30CA016672]
- NCI [P01CA049639]
Ask authors/readers for more resources
The degree of somatic hypermutation, determined as percent deviation of immunoglobulin heavy chain gene variable region sequence from the germline (IGHV%), is an important prognostic factor in chronic lymphocytic leukaemia (CLL). Currently, a cut-off of 2% deviation or 98% sequence identity to germline in IGHV sequence is routinely used to dichotomize CLL patients into mutated and unmutated groups. Because dissimilar IGHV% cut-offs of 1-5% were identified in different studies, we wondered whether no cut-off should be applied and IGHV% treated as a continuous variable. We analysed the significance of IGHV% in 203 CLL patients enrolled on the original frontline fludarabine, cyclophosphamide and rituximab (FCR) trial with a median of 10 years follow-up. Using the Cox Proportional Hazard model, IGHV% was identified as a continuous variable that is significantly associated with progression-free (PFS) and overall survival (OS) (P<0.001). Furthermore, we validated this finding in 323 patients treated with FCR off-protocol and in the total cohort (n=535). Multivariate analysis revealed a continuous trend. Higher IGHV% levels were incrementally associated with favorable PFS and OS in both FCR-treated cohorts (P<0.001, both cohorts). Taken together, our data suggest that IGHV% is a continuous variable in CLL patients treated with FCR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available