title: Second cancers and Richter transformation are the leading causes of death in patients with trisomy 12 chronic lymphocytic leukemia.
abstract: BACKGROUND
  Trisomy 12 (+12) is detected by fluorescence in-situ hybridization (FISH) analysis in up to 20% of patients with chronic lymphocytic leukemia (CLL). Patients with +12 are known to have unique features and to carry an intermediate prognosis.
  
  
  METHODS
  In order to better define this large group, we reviewed the characteristics of 250 untreated patients with +12.
  
  
  RESULTS
  When compared to 516 untreated patients negative for +12 by FISH, patients with +12 showed a higher incidence of thrombocytopenia, Richter transformation, and second malignant neoplasms (SMN), in addition to the expected increased rate of CD38 positivity and atypical immunophenotype. At a median follow-up of 51 months, 57% of patients needed first-line treatment; median time to first treatment was 38 months, and on multivariate analysis (MVA), it was found to be shorter in patients with advanced Rai stage, palpable splenomegaly, and deletion of 14q by conventional cytogenetic analysis. The overall response rate with first-line treatment was 94%. The median failure-free survival has not been reached, but on MVA, it was found to be shorter in patients whose disease responded in a manner other than complete remission or with FISH negativity for deletion 13q. The median overall survival for the entire group has not been reached, but MVA revealed it to be shorter in patients with an absolute lymphocyte count of > 30 × 10(9)/L or who developed SMN. Eighteen deaths have been observed so far, and Richter transformation and SMN were the leading causes of death (3 and 6, respectively).
  
  
  CONCLUSIONS
  Patients with +12 CLL show characteristic clinical and biologic features, and may benefit from increased surveillance for second cancers.
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Paolo
authors: P
authors: Strati
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Lynne V
authors: LV
authors: Abruzzo
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: William G
authors: WG
authors: Wierda
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Susan
authors: S
authors: O'Brien
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Alessandra
authors: A
authors: Ferrajoli
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: mkeating@mdanderson.org.
authors: Michael J
authors: MJ
authors: Keating
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D002881:Chromosomes, Human, Pair 12; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000401:mortality*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000401:mortality*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000401:mortality*; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000503:physiopathology; D014314:Trisomy / Q000235:genetics / Q000473:pathology*
chemical_list: D008562:Membrane Glycoproteins; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1
keywords: CLL; Prognosis; Richter transformation; Second cancers; Trisomy 12