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Impact of translocations in mutated IGHV CLL at diagnosis
A
Figure 2. Time to first treatment of patients with chronic lymphocytic leukemia. (A) Data are plotted for patients according to whether they had mutated or unmutated IGHV and a complex (≥3 aberrations) or non-complex karyotype. (B) Data are plotted for patients according to whether they did or did not have a translocation and whether they had a complex (≥3 aberrations) or non-complex karyotype.
B
This study also showed that CLL patients with a higher WBC count were likely to require treatment earlier than those with a lower WBC count. This is consistent with the findings of the study by Del Giudice et al.,33 who showed that in patients with Binet stage A CLL, a higher WBC count independently predicted a shorter time to treat- ment. Since a higher WBC count is consistent with a greater disease burden, this is compatible with the hypothesis that patients with a greater disease burden, regardless of other factors, have a shorter TFT.
A del(17p) has also been associated with a poor out- come.1,5,34-38 However, when detected within 1 year of diag- nosis, it was no longer significant in a multivariable analy- sis, independently of other variables. It is known that del(17p) frequently occurs with disease progression and that a higher frequency of del(17p) may be significant.39,40 We, therefore examined whether a higher frequency of this abnormality was significant. Using a 20% cutoff, higher frequency of del(17p) was also not significant in the multivariable analysis (P=0.51). Furthermore, our patients were within 1 year of diagnosis, which is consistent with the findings of Tam et al.,39 who showed that a del(17p) in asymptomatic CLL patients does not necessarily convey a poor prognosis. It also has been shown that del(17p) in association with a complex karyotype predicts a particu-
larly poor outcome.15,20,41 Although our patients with del(17p) were statistically associated with a complex kary- otype, 11/30 of our del(17p) cases did not have a complex karyotype. The loss of significance of del(17p) in a multi- variable analysis may in part reflect this.
In these studies, FISH abnormalities typically associated with a poor outcome (three copies of MYC, del(17p), del(11q) and three copies of BCL6) were more frequent in cases with a translocation and in those with a complex karyotype. Trisomy 12 showed no association with the presence of a translocation, but was more frequent in complex cases than in non-complex cases (35.9% and 21.4%, respectively; P=0.033). Deletions of 13q, typically associated with a good outcome, were more frequent in cases without a translocation and in non-complex cases, consistent with its association with a good outcome. However, del(13q) as a sole FISH abnormality was present in 12 cases with a translocation and in three cases with a complex karyotype, thus 15 of 119 cases (12.6%) with del(13q) as the only FISH-detected abnormality had poor metaphase cytogenetics, identifying these patients as pos- sibly not having the good prognosis typically associated with sole del(13q). Fifty-seven cases had no FISH abnor- mality (Table 5); ten of these had a translocation, and one had a complex karyotype. These results indicate the
haematologica | 2021; 106(6)
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