Gray, Leigh A.

Background Increased mobility and physical activity after successful vertebral augmentation procedure might increase the risk of new-onset fractures. Purpose To determine whether new-onset fracture following vertebroplasty is associated with specific type of physical activity. Material and Methods A total of 107 patients underwent at least two procedures of percutaneous vertebroplasty. Among them, 30 patients who sustained a post-vertebroplasty fracture(s), were stratified by fracture-causing activity and examined the incidence of the initial and post-vertebroplasty fractures, time to post-vertebroplasty fractures, duration of anti-osteoporotic therapy, T-score, and body mass index. Results The following percentages correspond to patients with fractures sustained pre- and post-vertebroplasty, respectively; spontaneous fractures in 17% and 7% ( P = 0.20), sitting in 7% and 3% ( P = 0.50), walking or standing in 7% and 20% ( P = 0.10), housework in 3% and 3% ( P > 0.99), coughing or sneezing in 0% and 20% ( P = 0.003), exercise in 7% and 17% ( P = 0.20), lifting in 10% and 17% ( P = 0.40) and falling in 50% and 13% ( P = 0.002). Different levels of activity were not significantly associated with time to incidence of post-vertebroplasty fractures. Anti-osteoporotic medications were administered to 33% of patients before vertebroplasty and 37% after the vertebroplasty ( P = 0.78); medications were administered to these groups for 16 and 25 months, respectively ( P = 0.39). Conclusion A significantly elevated risk of new onset fracture with increased physical activity was not identified. However, patients should be carefully counseled after vertebroplasty to optimize medical therapy for osteoporosis and also to use extreme care when engaging in even moderate physical activity.

Single-agent thalidomide (THAL) at “conventional” doses (> 100 mg/d) has been evaluated in myelofibrosis with myeloid metaplasia (MMM) based on its antiangiogenic properties and the prominent neoangiogenesis that occurs in MMM. THAL monotherapy at such doses produces approximately a 20% response rate in anemia but is poorly tolerated (an adverse dropout rate of > 50% in 3 months). To improve efficacy and tolerability, we prospectively treated 21 symptomatic patients (hemoglobin level < 10 g/dL or symptomatic splenomegaly) with MMM with low-dose THAL (50 mg/d) along with a 3-month oral prednisone (PRED) taper (beginning at 0.5 mg/kg/d). THAL-PRED was well tolerated in all enrolled patients, with 20 patients (95%) able to complete 3 months of treatment. An objective clinical response was demonstrated in 13 (62%) patients, all improvements in anemia. Among 10 patients who were dependent on erythrocyte transfusions, 7 (70%) improved and 4 (40%) became transfusion independent. Among 8 patients with thrombocytopenia (platelet count < 100 × 109/L), 6 (75%) experienced a 50% or higher increase in their platelet count. In 4 of 21 patients (19%), spleen size decreased by more than 50%. Responses observed were mostly durable after discontinuation of the PRED. The dose of THAL in this study (50 mg/d) was better tolerated than the higher doses used in previous studies. Adverse events associated with corticosteroid therapy were mild and transient. Clinical responses did not correlate with improvements in either intramedullary fibrosis or angiogenesis. THAL-PRED is well tolerated and preliminarily appears to be a promising drug regimen for treating cytopenias in patients with MMM.

In a phase 2 study, 23 patients with myelofibrosis with myeloid metaplasia were treated with imatinib mesylate at a constant dose of 400 mg/d. Treatment was held in 16 patients (70%), after 1 to 12 weeks, because of side effects (neutropenia, 6 patients; musculoskeletal pain, 5 patients; thrombocytosis, 4 patients; edema, 3 patients; diarrhea and hyperbilirubinemia, 1 patient). Including patients in whom retreatment at a reduced dose was possible, 11 patients (48%) were able to continue treatment beyond 3 months. None of the patients experienced a response in anemia, and only 2 had partial responses in splenomegaly. A greater than 50% increase in platelet count was documented in 11 (48%) patients, but not in those with baseline platelet counts of less than 100 × 109/L. In vitro, imatinib mesylate caused variable degrees of growth suppression of myeloid and erythroid progenitors that unfortunately did not translate into clinical benefit.

AbstractPatients with myelofibrosis with myeloid metaplasia (MMM) often experience debilitating constitutional symptoms such as drenching night sweats, profound fatigue, unexplained fevers, and unintentional weight loss. Tumor necrosis factor (TNF) contributes to organ fibrosis and hypercatabolic symptoms in a variety of disease states. We conducted an open-label pilot study of etanercept, a soluble TNF receptor, administered at a dose of 25 mg subcutaneously twice weekly for up to 24 weeks in 22 patients with MMM. Of 20 evaluable patients, 12 (60%) experienced an improvement in constitutional symptoms, and 4 (20%) had an objective response (improvement in peripheral cytopenias or spleen size). The degree of marrow fibrosis was unchanged, and only minor changes in overall marrow cellularity were observed. Toxicity was mild, with injection site reactions (20%) and minor infections (10%) as the most common side effects. One patient developed reversible pancytopenia. Etanercept may be useful for palliation of constitutional symptoms in MMM.