One Thousand Patients With Primary Myelofibrosis: The Mayo Clinic Experience

Abstract

Objective: To share our decades of experience with primary myelofibrosis and underscore the importance of outcomes research studies in designing clinical trials and interpreting their results. Patients and Methods: One thousand consecutive patients with primary myelofibrosis seen at Mayo Clinic between November 4, 1977, and September 1, 2011, were considered. The International Prognostic Scoring System (IPSS), dynamic IPSS (DIPSS), and DIPSS-plus were applied for risk stratification. Separate analyses were included for patients seen at time of referral (Nϭ1000), at initial diagnosis (Nϭ340), and within or after 1 year of diagnosis (Nϭ660). Results: To date, 592 deaths and 68 leukemic transformations have been documented. Parameters at initial diagnosis vs time of referral included median age (66 vs 65 years), male sex (61% vs 62%), red cell transfusion need (24% vs 38%), hemoglobin level less than 10 g/dL (38% vs 54%), platelet count less than 100 ϫ 10 9 /L (18% vs 26%), leukocyte count more than 25 ϫ 10 9 /L (13% vs 16%), marked splenomegaly (21% vs 31%), constitutional symptoms (29% vs 34%), and abnormal karyotype (31% vs 41%). Mutational frequencies were 61% for JAK2V617F, 8% for MPLW515, and 4% for IDH1/2. DIPSS-plus risk distributions at time of referral were 10% low, 15% intermediate-1, 37% intermediate-2, and 37% high. The corresponding median survivals were 17.5, 7.8, 3.6, and 1.8 years vs 20.0, 14.3, 5.3, and 1.7 years for patients younger than 60 years of age. Compared with both DIPSS and IPSS, DIPSS-plus showed better discrimination among risk groups. Five-year leukemic transformation rates were 6% and 21% in low-and high-risk patients, respectively. Conclusion: The current document should serve as a valuable resource for patients and physicians and provides context for the design and interpretation of clinical trials.

Ruxolitinib leads to improvement of pulmonary hypertension in patients with myelofibrosis

“…1 Pulmonary hypertension (PH) is an indolent and progressive vascular lung disease that can complicate the clinical course of patients with MF, occurring in approximately 30% of MF patients. 2,3 The presence of MF-associated PH is correlated with poor survival. 4-7 PH manifests with nonspecific symptoms such as dyspnea on exertion and fatigue and can be detected by showing elevated right ventricular systolic pressure (RVSP)435 mm Hg, right atrium enlargement and tricuspid regurgitation velocity X2.5 m/s using echocardiography.…”

New Сytogenetic Approaches in Patients with Primary Myelofibrosis

“…1), прогностическая значимость которых при ПМФ была показана неодно-кратно [30][31][32][33][34][35]. Согласно опубликованным данным, успешные цитогенетические исследования костного мозга до последнего времени удавалось проводить лишь у 15-30 % пациентов [16][17][18][19][20][21][22][23]. Результаты работы удалось существенно улучшить недавно, когда для цито-генетического анализа стали использовать 48-часовые нестимулированные культуры крови [24].…”

“…Основной акцент делался на повреждения хромосом 3, 1 и 13 [9,13]. Масштабные цитогенетические исследо-вания при ПМФ были выполнены относительно недавно [16][17][18][19][20][21][22][23]. Они показали, что у этих больных чаще других встречаются делеции длинного плеча хромосом 20, 13 и 11, а также дупликации длинного плеча хромосомы 1.…”

Leukemic transformation in myeloproliferative neoplasms: Therapy-related or unrelated?

“…The overall risk of leukemic transformation in patients with PMF is around 20% [57,58]. Patients with post-PV and post-ET myelofibrosis have a similar risk of leukemic transformation [59].…”