The Dohner fluorescence in situ hybridization prognostic classification of chronic lymphocytic leukaemia (CLL): the CLL Research Consortium experience

Abstract

SummaryThis study revisited the Dohner prognostic hierarchy in a cohort of 1585 well-documented patients with chronic lymphocytic leukaemia. The duration of both time to first treatment (TTFT) and overall survival (OS) were significantly longer than observed previously, and this is at least partly due to improved therapeutic options. Deletion 13q remains the most favourable prognostic group with median TTFT and OS from fluorescence in situ hybridization (FISH) testing of 72 months and >12 years, respectively. Deletion 11q had the poorest median TTFT (22 months) and 17p deletion the poorest median OS (5 years). The percentages of abnormal nuclei were significantly associated with differential TTFT for the trisomy 12, 13q and 17p deletion cohorts but not for the 11q deletion cohort. From the date of the first FISH study, patients with >85% 13q deletion nuclei had a notably shorter TTFT (24 months). Patients with ≤20% 17p deletion nuclei had longer median TTFT and OS from the date of the first FISH study (44 months and 11 years), and were more likely to be IGHV mutated.

Mutational status of IGHV is the most reliable prognostic marker in trisomy 12 chronic lymphocytic leukemia

“…Previous authors have demonstrated that a high proportion of cells bearing tris12 is associated with a worse outcome. 3,13 In the series herein, we could not confirm this feature, neither with tris12 evaluated as a continuous variable, nor as a dichotomous variable applying the cut-off point at 60% of tris12-bearing nuclei, as previously suggested.…”

“…3 Other reports suggest a certain degree of clinical heterogeneity, with a higher incidence of second malignant neoplasms 4 and Richter transformation. 4 although the real impact of these CLL negative prognosticators in the tris12 setting remain to be fully elucidated.…”

“…1,2 Within the hierarchical model proposed by Döhner et al, 3 trisomy 12 CLL (tris12 CLL) carry an intermediate prognostic risk, with median overall survival (OS) and time to first treatment (TTFT) usually shorter than those cases bearing the 13q14 deletion (del13q) or the so-called normal karyotype cases (i.e., lacking tris12, del13q, 11q22 deletion -del11q-and 17p13 deletiondel17p-), but longer than CLL characterized by del11q and del17p. 3 Other reports suggest a certain degree of clinical heterogeneity, with a higher incidence of second malignant neoplasms 4 and Richter transformation.…”

“…Tiziana D'Agaro, 1 Michaela Cerri, 2 Annalisa Chiarenza, 3 Kari G. Chaffee, 4 Adalgisa Condoluci, 5 Giovanni D'Arena, 6 Michele Spina, 7 Francesco Zaja, 8 Gabriele Pozzato, 9 Francesco Di Raimondo, 3 Davide Rossi, 5 Giovanni Del Poeta, 10 …”

Karyotypic complexity rather than chromosome 8 abnormalities aggravates the outcome of chronic lymphocytic leukemia patients withTP53aberrations

“…These aberrations are associated with distinct clinical outcome [1, 2]. In particular, del(17p) cases have the worst clinical outcome and the shortest overall survival (OS).…”