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. 2024 Mar 8;16(6):1095.
doi: 10.3390/cancers16061095.

Chronic Lymphocytic Leukemia (CLL) with Borderline Immunoglobulin Heavy Chain Mutational Status, a Rare Subgroup of CLL with Variable Disease Course

Francesco Angotzi  1 , Alessandro Cellini  1 , Valeria Ruocco  1 , Chiara Adele Cavarretta  1 , Ivan Zatta  1 , Andrea Serafin  1 , Stefano Pravato  1 , Elisa Pagnin  1 , Laura Bonaldi  2 , Federica Frezzato  1 , Monica Facco  1 , Francesco Piazza  1 , Livio Trentin  1 , Andrea Visentin  1
Affiliations

Chronic Lymphocytic Leukemia (CLL) with Borderline Immunoglobulin Heavy Chain Mutational Status, a Rare Subgroup of CLL with Variable Disease Course

Francesco Angotzi et al. Cancers (Basel). .

Abstract

Chronic lymphocytic leukemia (CLL) exhibits substantial variability in disease course. The mutational status of the B-cell receptor immunoglobulin heavy variable (IGHV) chain is a critical prognostic factor, categorizing patients into mutated (M-IGHV) and unmutated (U-IGHV) groups. Recently, a third subgroup with borderline mutational status (BL-IGHV) has been identified, comprising approximately 5% of CLL cases. This study retrospectively analyzes the outcomes of 30 BL-IGHV mutated patients among a cohort of 653 CLL patients, focusing on time to first treatment (TTFT) and overall survival (OS). BL-IGHV patients had a short TTFT similar to U-IGHV patients (median 30.2 vs. 34 months; p = 0.9). Conversely, the OS of BL-IGHV patients resembled M-IGHV patients (median NR vs. 258 months; p = 1). Despite a similar incidence in unfavorable prognostic factors, the TTFT was shorter compared to other published cohorts. However, striking similarities with other experiences suggest that BL-IGHV mutated patients share common biological characteristics, biased IGHV gene usage and BCR subset frequency. These findings also underscore the need for multicentric efforts aggregating data on BL-IGHV CLL in order to elucidate its disease course and optimize therapeutic approaches for this rare subgroup. Until then, predicting outcomes and optimal management of BL-IGHV CLL will remain challenging.

Keywords: IGHV mutational status; borderline mutated; chronic lymphocytic leukemia.

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Conflict of interest statement

AV attended advisory boards organized by Janssen, Abbvie, AstraZeneca, Beigene, and CSL Behring. LT received research funding from Abbvie, Gilead, Janssen, Astrazeneca, and Takeda, and attended advisory boards by Janssen, Takeda, Abbvie, AstraZeneca, Beigene, and Octapharama. FP attended advisory boards by Janssen, Roche, and Incyte.

Figures

Figure 1
Figure 1
(A) Survival curves for time to first treatment (TTFT) and (B) for overall survival; the inserts show hazard ratios and their confidence intervals for BL-IGHV patients compared to M-IGHV and U-IGHV patients.
See this image and copyright information in PMC

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