Thalidomide treatment in myelofibrosis with myeloid metaplasia

Abstract

Summary. Myelofibrosis with myeloid metaplasia (MMM) is uniquely characterized by macroscopic bone marrow stromal changes that are believed to be both reactive and cytokine mediated. Furthermore, a prognostically detrimental increase in bone marrow angiogenesis has recently been demonstrated. These observations suggest a potential therapeutic role for agents that are inhibitory to angiogenesis as well as cytokines that are pathogenetically implicated in MMM. In a prospective study of 15 patients with MMM, thalidomide treatment, starting at a dose of 200 mg/d, resulted in increased platelet counts (12 of 15 patients), increased haemoglobin level (3 of 15), a modest decrease in spleen size (3 of 12), increased bone marrow megakaryopoiesis (5 of 9) and decreased bone marrow angiogenesis (2 of 9). Undesirable haematological effects included pericardial extramedullary haematopoiesis in one patient, marked leucocytosis in two patients and extreme thrombocytosis in three patients. The thrombocytosis occurred in both patients with post‐thrombocythaemic myeloid metaplasia (PTMM) and was also associated with higher baseline levels of circulating CD34+ cells. Previously described toxicities of thalidomide were seen in the majority of patients and dose escalation to 400 mg/d was permitted in only two patients. In contrast, toxicity‐related dose reductions to 50 mg/d did not appear to lessen drug efficacy. We conclude that thalidomide has both beneficial and potentially adverse biological activity in MMM. A lower dose of the drug might be more tolerable without compromising therapeutic value. Patients with PTMM and/or markedly increased circulating CD34+ cell counts might be susceptible to thalidomide‐induced thrombocytosis.

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.…”

Myeloproliferative neoplasms: A decade of discoveries and treatment advances

“…2). First-line drugs of choice in such patients are hydroxyurea for symptomatic splenomegaly [125], androgens preparations [126], prednisone [126], danazol [127], thalidomide 6 prednisone [128][129][130] or lenalidomide 6 prednisone [131,132] for symptomatic anemia, splenectomy (or splenic radiotherapy for nonsurgical candidates) for splenomegaly that is resistant to conventional drug therapy [133], involved field radiotherapy for nonhepatosplenic EMH might and ruxolitinib for severe constitutional symptoms that are resistant to hydroxyurea therapy [133].…”

Myelofibrosis with Myeloid Metaplasia: New Developments in Pathogenesis and Treatment

“…Due to its pleotropic effects on cytokine production and its inhibitory effects on angiogenesis, thalidomide has received considerable attention as a therapeutic agent for MMM (55) as has been the case with multiple myeloma (56,57). A dose of 200 mg per day leads to significant improvements in anemia and reduction of splenomegaly in a substantial proportion of patients (58). Patients seem to tolerate low doses of the drug well although 20% of them experience a myeloproliferative response characterized by leukocytosis and thrombocytosis (55).…”