title: Thalidomide versus placebo in myeloid metaplasia with myelofibrosis: a prospective, randomized, double-blind, multicenter study.
abstract: OBJECTIVE
  In non-randomized studies, thalidomide appeared to be effective in myeloid metaplasia with myelofibrosis (MMM). We compared thalidomide to placebo for treatment of anemia in MMM.
  
  
  METHODS
  A prospective phase II B, randomized double-blind multicenter trial comparing thalidomide 400 mg/d with placebo for 180 days was conducted in 52 anemic patients (hemoglobin pounds Sterling 9 g/dL or transfused). The main outcome measure was a 2 g/L increase in hemoglobin or 20% reduction in transfusions.
  
  
  RESULTS
  In the thalidomide group only 10 patients completed 6 months of treatment. At 180 days, in an intention-to-treat analysis, no difference was observed between the thalidomide and placebo groups as regards improvement of hemoglobin levels (one patient in each group) or reduction of red blood cell transfusions (three vs five patients, respectively). The spleen size, determined by ultrasonography, increased significantly less in the thalidomide group than in the placebo group (p < 0.05). Thalidomide had no apparent benefit on the Dupriez score, the severity score, survival, death, or any other clinical or biological parameter. Somnolence, gastro-intestinal signs, weight gain, and edema were significantly more frequent in the thalidomide group. Outpatient discontinuation of thalidomide was significantly correlated with a high severity score > 4 (odds ratio, OR = 16; p < 0.01), and g-glutamyl transferase levels > 40 IU/L (OR = 12; p < 0.05).
  
  
  CONCLUSIONS
  Thalidomide (200-400 mg/d) does not demonstrate substantial efficacy in anemic MMM patients. The natural history of disease in the placebo group revealed spontaneous periods of remission of anemia. Tolerance of thalidomide was significantly correlated wih the severity and liver involvement of the disease.
authors.affiliation: Groupe Ouest-Est Leucémies et Maladies du Sang. jean-francois.abgrall@chu-brest.fr
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Abgrall
authors.forename: Isabelle
authors.initials: I
authors.lastname: Guibaud
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Bastie
authors.forename: Michel
authors.initials: M
authors.lastname: Flesch
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Rossi
authors.forename: Laurence
authors.initials: L
authors.lastname: Lacotte-Thierry
authors.forename: Françoise
authors.initials: F
authors.lastname: Boyer
authors.forename: Philippe
authors.initials: P
authors.lastname: Casassus
authors.forename: Borhane
authors.initials: B
authors.lastname: Slama
authors.forename: Christian
authors.initials: C
authors.lastname: Berthou
authors.forename: Philippe
authors.initials: P
authors.lastname: Rodon
authors.forename: Michel
authors.initials: M
authors.lastname: Leporrier
authors.forename: Bruno
authors.initials: B
authors.lastname: Villemagne
authors.forename: Chantal
authors.initials: C
authors.lastname: Himberlin
authors.forename: Kamel
authors.initials: K
authors.lastname: Ghomari
authors.forename: Fabrice
authors.initials: F
authors.lastname: Larosa
authors.forename: Florence
authors.initials: F
authors.lastname: Rollot
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Dugay
authors.forename: Christian
authors.initials: C
authors.lastname: Allard
authors.forename: Michel
authors.initials: M
authors.lastname: Maigre
authors.forename: Françoise
authors.initials: F
authors.lastname: Isnard
authors.forename: Robert
authors.initials: R
authors.lastname: Zerbib
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Cauvin
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D004311:Double-Blind Method; D005602:France; D006801:Humans; D010919:Placebos; D055728:Primary Myelofibrosis / Q000150:complications* / Q000188:drug therapy*; D015203:Reproducibility of Results; D012107:Research Design; D013792:Thalidomide / Q000627:therapeutic use* / Q000633:toxicity
chemical_list: D020533:Angiogenesis Inhibitors; D010919:Placebos; D013792:Thalidomide