Redefining the prognostic likelihood of chronic lymphocytic leukaemia patients with borderline percentage of immunoglobulin variable heavy chain region mutations

• Published in: British journal of haematology Vol. 189; no. 5; pp. 853 - 859
• Main Authors: Raponi, Sara, Ilari, Caterina, Della Starza, Irene, Cappelli, Luca V., Cafforio, Luciana, Piciocchi, Alfonso, Arena, Valentina, Mariglia, Paola, Mauro, Francesca R., Gentile, Massimo, Cutrona, Giovanna, Moia, Riccardo, Favini, Chiara, Morabito, Fortunato, Rossi, Davide, Gaidano, Gianluca, Guarini, Anna, Del Giudice, Ilaria, Foà, Robin
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.06.2020
• Subjects: ADP-ribosyl Cyclase 1 - analysis; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm - analysis; chronic lymphocytic leukaemia; Chronic lymphocytic leukemia; Diagnosis; Female; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Genes, Immunoglobulin Heavy Chain; Hematology; Humans; Immunoglobulin Heavy Chains - genetics; immunoglobulin variable heavy chain; Immunoglobulin Variable Region - genetics; Immunoglobulins; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - mortality; Leukemia, Lymphocytic, Chronic, B-Cell - therapy; Male; Membrane Glycoproteins - analysis; Middle Aged; Mutation; Patients; Prognosis; Retrospective Studies; somatic hypermutation; Somatic Hypermutation, Immunoglobulin; Time-to-Treatment; chronic lymphocytic leukaemia; somatic hypermutation; immunoglobulin variable heavy chain; prognosis
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.16434

Summary In chronic lymphocytic leukaemia (CLL), caution is warranted regarding the clinical implications of immunoglobulin variable heavy chain region (IGHV) rearrangements with a ‘borderline’ (BL) percentage of mutations (i.e. 97–97·9% IGHV identity). We analysed the IGHV mutational status in 759 untreated CLL patients (cohort 1). BL‐CLL (n = 36, 5%) showed a time to first treatment (TFT) similar to that of M‐CLL (n = 338) and significantly longer than that of UM‐CLL (n = 385), despite the enrichment in subset #2 cases. In fact, CLLs belonging to subset #2 (n = 15/759, 2%) were significantly more frequent among BL‐CLLs (n = 5/36, 14%), with a brief TFT. TFT of BL‐CLL remained comparable to that of M‐CLL also considering the 327 CLL patients evaluated at diagnosis. These findings were then validated in an independent cohort 2 of 759 newly diagnosed CLL patients (BL‐CLL: n = 11, 1·4%) and in all newly diagnosed patients from cohorts 1 and 2 (n = 1 086, 84% stage A; BL‐CLL: n = 47, 4·3%). BL‐CLL at diagnosis showed a biological profile comparable to that of M‐CLL with a low frequency of unfavourable prognostic markers, except for a significant enrichment in subset #2. Our data suggest that the prognosis of BL‐CLL is good and similar to that of M‐CLL, with the exception of subset #2 cases.