Page 34 - Haematologica June

F. Autore et al.
Table 2. Clinical outcomes of patients with +12 chronic lymphocytic leukemia.
5 were hematologic malignancies, and 17 were non- hematologic malignancies. In the multivariable model, an absolute lymphocyte count of more than 30x109/L (HR 14.5; P=0.04) and development of a second malignant neoplasm (HR 23.8; P=0.002) remained independently associated with OS. A correlation between CLL and sec- ond malignant neoplasms has been reported, but the mechanism linking +12 to the onset of second neoplasms remains unknown.98 Eighteen patients (7.2%) died during the observation time, 15 of whom had received treatment for CLL. Seven patients died of CLL-related (n=4) or Richter syndrome-related (n=3) causes; 6 patients died of second neoplasms, and 5 died of unrelated causes. There was no significant difference in distribution of the causes of death between treated and untreated patients (P=0.24). The mortality of patients with +12 was only partly related to complications of CLL; the leading causes of death were Richter syndrome and second malignant neoplasms. However, given the evidence of a worse out- come for second malignant neoplasms in CLL, increased surveillance of patients in this specific group should be considered.99
Conclusions
The unique morphology, immunophenotype, and cyto- genetics of +12 CLL easily distinguish it from other CLL cytogenetic subtypes. +12 in CLL confers an intermediate prognostic risk, characterized by a median TTFT of 33 months and a median OS of 114 months. Genomic alter- ations, especially NOTCH1 mutations, can portend a worse prognosis and an increased risk of Richter syn- drome.
Acknowledgments
The authors would like to thank Sarah Bronson, ELS Department of Scientific Publications The University of Texas MD Anderson Cancer Center for editorial assistance.
Outcome González-Gascón y Marín (n=289)82
Strati (n=250)25
51 (1-105)
57.0%
38 (27-48)
7.0% Not reached
Median follow up (range), months
Treatments
Median TTFT (95% CI), months
Deaths
Median OS (95% CI), months
41 (1-197)
61.0%
42 (34-49)
21.8% 129
(100 to 158)
936
CI: Confidence Interval; TTFT: time to first treatment; OS: overall survival.
up of 51 months (range 1-105 months), 142 patients (56.8%) required initiation of treatment. The median TTFT was 38 months (95%CI: 27-48 months), signifi- cantly shorter than that of FISH-negative patients (82 months; P<0.001). The multivariable model for TTFT showed that a Rai stage of III-IV [Hazard Ratio (HR) 3.3; P=0.02], palpable splenomegaly (HR 2.3; P=0.007), and chromosome banding analysis positivity for del14q (HR 3.5; P=0.004) were independently associated with TTFT. The estimated median OS was not reached, as only 18 patients died, and did not differ significantly between patients with or without +12 by FISH (P=0.22).
Followed over time, 6 of these patients (2.4%) devel- oped histologically confirmed Richter syndrome after a median ten months (95%CI: 5-15 months) from diagno- sis. This incidence was significantly higher in treated than in untreated patients (4% vs. 0%; P=0.04) and in patients with +10 compared with the control cohort of patients with normal karyotype (2.0% vs. 0.4%; P=0.02). Twenty- two patients (8.8%) developed a malignancy other than Richter syndrome after a median of 19 months (95%CI: 6-32 months) from diagnosis. Among second neoplasms,
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