title: Efficacy and safety of cytoreductive therapies in patients with essential thrombocythaemia aged >80 years: an interim analysis of the EXELS study.
abstract: BACKGROUND
  The median age of patients diagnosed with essential thrombocythaemia (ET) is 65-70 years but the management of very elderly patients (aged >80 years) with ET has not been well characterized.
  
  
  OBJECTIVE
  This study aimed to document the treatment patterns of very elderly patients with ET in a multinational, real-world setting.
  
  
  METHODS
  EXELS (Evaluation of Xagrid Efficacy and Long-term Safety) is a phase IV observational study, designed to monitor the efficacy and safety of cytoreductive therapies in clinical practice. In total, 3,598 high-risk patients with ET were recruited from May 2005 to April 2009, in 13 European countries. Data were collected at registration and every 6 months thereafter for 5 years. This analysis was performed on a data-cut taken approximately 2 years after the last patient was registered.
  
  
  METHODS
  In total, 395 patients aged >80 years at registration into EXELS were included in the analysis; of these, 42.2 % had experienced a previous thrombohaemorrhagic event.
  
  
  RESULTS
  At registration, the most frequently prescribed cytoreductive therapy for patients aged >80 years was hydroxycarbamide (HC), which accounted for 82.8 % of patients whereas anagrelide use was less frequent (8.6 %). Very elderly patients were more likely to be switched from anagrelide than from HC (47.1 vs. 17.4 %; 95 % confidence interval for difference in proportion 12.4-46.9; Chi-squared test p < 0.001). Median platelet count during treatment was ~430 × 10(9)/L. In patients aged >80 years, the main reason for switch was intolerance/side effects (34.1 %); 0/16 patients reported treatment with anagrelide was non-efficacious compared with 8/57 (14 %) patients receiving HC, and 7/16 (43.8 %) anagrelide patients switched because of intolerance versus 18/57 (31.6 %) patients receiving HC. At least one predefined clinical event (PDE) was experienced by 27.3 % of patients aged >80 years. The most common PDEs reported in the very elderly age group were death (non-PDE related; 11.1 %), other cardiovascular symptoms (5.8 %), haematological transformation (3.8 %), congestive heart failure (3.3 %), myocardial infarction and angina (2.8 %), and thromboembolic events (6.3 %).
  
  
  CONCLUSIONS
  Well-tolerated and effective cytoreductive therapy has been achieved in patients aged >80 years by following individual treatment modalities that appear in agreement with the recent European LeukemiaNet (ELN) guidelines.
authors.affiliation: AP-HP, Hôpital Saint-Louis, Centre d'Investigations Cliniques, Paris, France. jean-jacques.kiladjian@sls.aphp.fr
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Kiladjian
authors.forename: Carlos
authors.initials: C
authors.lastname: Besses
authors.forename: Martin
authors.initials: M
authors.lastname: Griesshammer
authors.forename: Luigi
authors.initials: L
authors.lastname: Gugliotta
authors.forename: Claire
authors.initials: C
authors.lastname: Harrison
authors.forename: Ruth
authors.initials: R
authors.lastname: Coll
authors.forename: Jonathan
authors.initials: J
authors.lastname: Smith
authors.forename: Gunnar
authors.initials: G
authors.lastname: Birgegård
mesh_terms: D000367:Age Factors; D000369:Aged, 80 and over; D000704:Analysis of Variance; D016009:Chi-Square Distribution; D057915:Drug Substitution; D005060:Europe; D005260:Female; D006401:Hematologic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D010976:Platelet Count; D011446:Prospective Studies; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D013920:Thrombocythemia, Essential / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006401:Hematologic Agents; D011799:Quinazolines; C021139:anagrelide; D006918:Hydroxyurea