Responses to Thalidomide Combined with Prednisone Therapy for Myelofibrosis with Myeloid Metaplasia.

Myelofibrosis with myeloid metaplasia (MMM) is currently classified as a classic (i.e. not yet molecularly defined) myeloproliferative disorder (MPD), along with essential thrombocythemia (ET) and polycythemia vera (PV). All three MPDs represent stem-cell-derived clonal myeloproliferation that, in the case of MMM, is accompanied by an intense bone marrow stromal reaction that includes collagen fibrosis, osteosclerosis, and angiogenesis. To present the results of a long-term analysis of 2 sequential phase 2 trials of thalidomide (alone or in combination) for palliation of myelofibrosis with myeloid metaplasia (MMM). We analyzed (March 2003 to August 2005) initial and long-term outcomes from 33 patients with symptomatic MMM who had enrolled in either our thalidomide single-agent trial (n=12) or our trial of low-dose thalidomide (50 mg/d) combined with prednisone (n=21). Among the 33 study patients, 18 (54%) showed some improvement in their clinical course. Response rates for specific end points included improvements in anemia (12 of 33 [36%]), thrombocytopenia (8 of 12 [66%]), or splenomegaly (5 of 30 [17%]). The combination of low-dose thalidomide and prednisone, as opposed to single-agent thalidomide, was better tolerated and more efficacious. After a median follow-up of 17 months (range, 9–27 months), 10 of 33 patients (33%) showed an ongoing response, including 8 patients in whom protocol treatment has been discontinued for a median of 21 months (range, 16–27 months). Durable treatment responses were documented for only anemia and thrombocytopenia. Treatment response was not affected by the baseline status of bone marrow fibrosis, angiogenesis, osteosclerosis, cytogenetics. Unusual drug effects, all reversible, included leukocytosis (8 patients) and/or thrombocytosis (6 patients). Thalidomide (alone or combined with prednisone) is an effective first-line treatment of symptomatic anemia or thrombocytopenia in MMM. Thalidomide-based therapy has the potential to produce durable responses in MMM-associated cytopenias, even after discontinuation of the drug.