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

Sara Raponi, Caterina Ilari, Irene Della Starza, Luca V. Cappelli, Luciana Cafforio, Alfonso Piciocchi, Valentina Arena, Paola Mariglia, Francesca R. Mauro, Massimo Gentile, Giovanna Cutrona, Riccardo Moia, Chiara Favini, Fortunato Morabito, Davide Rossi, Gianluca Gaidano, Anna Guarini, Ilaria Del Giudice, Robin Foà

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalBritish Journal of Haematology
DOIs
Publication statusAccepted/In press - Jan 1 2020

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Keywords

  • chronic lymphocytic leukaemia
  • immunoglobulin variable heavy chain
  • prognosis
  • somatic hypermutation

ASJC Scopus subject areas

  • Hematology

Cite this

Raponi, S., Ilari, C., Della Starza, I., Cappelli, L. V., Cafforio, L., Piciocchi, A., Arena, V., Mariglia, P., Mauro, F. R., Gentile, M., Cutrona, G., Moia, R., Favini, C., Morabito, F., Rossi, D., Gaidano, G., Guarini, A., Del Giudice, I., & Foà, R. (Accepted/In press). Redefining the prognostic likelihood of chronic lymphocytic leukaemia patients with borderline percentage of immunoglobulin variable heavy chain region mutations. British Journal of Haematology. https://doi.org/10.1111/bjh.16434