ArticleBritish journal of haematology2018
The absolute percent deviation of IGHV mutation rather than a 98% cut-off predicts survival of chronic lymphocytic leukaemia patients treated with fludarabine, cyclophosphamide and rituximab.
Article in British journal of haematology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Trial
- Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia.The New England journal of medicine · 2019Trial
- IGHV Mutational Status in a Cohort of Bulgarian CLL Patients: High Unmutated CLL Prevalence in North-East Bulgaria.Balkan journal of medical genetics : BJMG · 2024Article
- Article
- A novel next-generation sequencing capture-based strategy to report somatic hypermutation status using genomic regions downstream to immunoglobulin rearrangements.Haematologica · 2023Article
- Review
- Unmutated IGHV1-69 CLL Clone Displays a Distinct Gene Expression Profile by a Comparative qRT-PCR Assay.Biomedicines · 2022Article
- Impact of the Types and Relative Quantities of IGHV Gene Mutations in Predicting Prognosis of Patients With Chronic Lymphocytic Leukemia.Frontiers in oncology · 2022Article
- Review
- Immunoglobulin heavy variable somatic hyper mutation status in chronic lymphocytic leukaemia: on the threshold of a new era?British journal of haematology · 2020Article
- IGHV mutational status and outcome for patients with chronic lymphocytic leukemia upon treatment: a Danish nationwide population-based study.Haematologica · 2020Article
- Review
- 98% IGHV gene identity is the optimal cutoff to dichotomize the prognosis of Chinese patients with chronic lymphocytic leukemia.Cancer medicine · 2020Article
- Evaluation of Somatic Hypermutation Status in Chronic Lymphocytic Leukemia (CLL) in the Era of Next Generation Sequencing.Frontiers in cell and developmental biology · 2020Review
- Immunoglobulin somatic hypermutation has clinical impact in DLBCL and potential implications for immune checkpoint blockade and neoantigen-based immunotherapies.Journal for immunotherapy of cancer · 2019Article
- Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: results from 3 UK clinical trials.Blood advances · 2019Article
- Observational
- Clinicopathologic and molecular features in hairy cell leukemia-variant: single institutional experience.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2018Article
- Prognostic Factors in the Era of Targeted Therapies in CLL.Current hematologic malignancy reports · 2018Review
- Why Is the Immunoglobulin Heavy Chain Gene Mutation Status a Prognostic Indicator in Chronic Lymphocytic Leukemia?Acta haematologica · 2018Review
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Authors and funding
19 authors at 3 institutions in 3 countries.
Funding
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.