Bone marrow effects of anagrelide therapy in patients with myelofibrosis with myeloid metaplasia.
In a prospective study investigating the therapeutic role of anagrelide in myelofibrosis with myeloid metaplasia, 20 patients received anagrelide in daily oral doses of 0.5-3 mg. 17 patients were evaluable and received anagrelide for a median of 2 years (range 0.5-4 years). No patient had a clinically appreciable benefit. Bone marrow (BM) examinations at baseline and after 6 and 12 months of treatment were available for 17, 17 and 12 patients, respectively. In all evaluable cases, BM megakaryocyte number increased after 6 months of anagrelide treatment. Also, Ulex europaeus agglutinin-1 staining of megakaryocytes revealed a left-shifted maturation pattern in most patients with a platelet response to anagrelide. However, megakaryocyte staining intensity for transforming (TGF-beta) and platelet-derived (PDGF) growth factors was not affected consistently by treatment. No patient had a >/=2 grade change in either BM fibrosis or osteosclerosis. These in-vivo data support our previous in-vitro observations that anagrelide interferes with megakaryocyte maturation rather than proliferation. Lack of a positive treatment effect is consistent with the finding that anagrelide did not significantly alter megakaryocyte expression of TGF-beta and PDGF.
Yoon
S Y
SY
Division of Hematopathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA.
Li
C Y
CY
Mesa
R A
RA
Tefferi
A
A
D000368:Aged; D001792:Blood Platelets / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010976:Platelet Count; D055728:Primary Myelofibrosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D011799:Quinazolines / Q000627:therapeutic use*
D010975:Platelet Aggregation Inhibitors; D011799:Quinazolines; C021139:anagrelide