Clinical efficacy and antiangiogenic activity of thalidomide in myelofibrosis with myeloid metaplasia. A pilot study

Abstract

Increased neoangiogenesis has been reported in myelofibrosis with myeloid metaplasia (MMM). Thus we studied the effects of thalidomide, an antiangiogenic drug, in 12 MMM patients. Before treatment, all the cases showed a significantly increased micro-vessel density (MVD); in all eight tested cases bFGF and VEGF plasma levels were higher than controls. All patients presented disease progression in the last 3 months with standard therapy, regarding splenomegaly, anemia and/or thrombocytopenia and/or hyperleukocytosis. Thalidomide was administered at daily doses increasing from 100 to 600 mg. Eleven out of 12 patients were evaluable. No progression of disease was seen during the treatment in any case. In particular, spleen size decreased in 7/11 patients, anemia improved in 3/4 (two are now transfusion independent), thrombocytopenia in 2/2 and hyperleukocytosis in 2/5 patients. Side-effects were frequent, although not severe. After treatment, VEGF and bFGF plasma levels varied widely and in selected cases decreased. In particular, VEGF and/or bFGF decreased in 4/5 responders and in 1/3 non-responders. Moreover, MVD significantly decreased in all the responders evaluated after treatment. We conclude that thalidomide is a feasible therapy in MMM patients and looks promising at least to control the growth progression of disease.

Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high‐risk myelodysplastic syndrome, and myeloproliferative disorders

“…This was also the case in the series by Tefferi et al In their study, 11 patients (48%) experienced increases in platelet counts, but there was no improvement in patients with pretreatment platelet counts less than 100 ϫ 10 9 /L. Thus, earlier treatment with imatinib and/or the use of imatinib in combination with other agents (e.g., thalidomide [33][34][35] ) might be more effective.…”

Thalidomide therapy for myelofibrosis with myeloid metaplasia

“…22,34 No direct correlation between reduction in bone marrow vascularity and outcome was detected in our study, similar to the findings from initial studies of thalidomide in patients with previously treated MM. 20 Decreases in levels of VEGF and bFGF occurred during therapy but did not correlate directly with response ( Figs.…”

Chronic idiopathic myelofibrosis: independent prognostic importance of bone marrow microvascular density evaluated by CD105 (endoglin) immunostaining

“…[39][40][41][42][43][44][45] With regard to therapeutic aspects, clinical improvement offered by treatment with the antiangiogenetic drug thalidomide has been recently reported in CIMF, although the efficacy of this drug in reducing MVD is still uncertain. 9,46 It is noteworthy that a recent preliminary report focused on CD105 suggested the efficacy of anti-CD105 MoAb therapy, in synergy with cyclophosphamide, in reducing tumor size in human skin/SCID (severe combined immunodeficiency) mouse chimeras bearing human breast cancer. 47 CD105 may represent a target for antiangiogenic therapy; 48 this belief is also supported by the concept that endothelial cells of tumor microvessels may be more susceptible to killing effects of anti-CD105 immunoconjugates than the vascular endothelium of normal tissues.…”