Ayalew Tefferi, M.D., with the Department of Hematology at Mayo Clinic in Rochester, Minn., discusses the results of a study of 1,000 patients who have primary myelofibrosis.
Researchers found that when patients with myelofibrosis present, their clinical features are not at a steady state and usually progress within the first few months of the diagnosis. It is best to wait a several months before providing a prognostic score.
Many patients with primary myelofibrosis can live a long life (exceeding 15 years) and patients who won’t live that long can be identified.
The most recent version of DIPSS-plus scoring system performed much better than prior versions, helping researchers to determine what proportion of patients with myelofibrosis are suitable for therapies. More than 50 percent of patients require observation alone.
A description of the study is included in the January 2012 issue of Mayo Clinic Proceedings.
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 Nov. 4, 1977, and Sept. 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 (N=1000), at initial diagnosis (N=340), and within or after 1 year of diagnosis (N=660).
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 × 109/L (18% vs 26%)
- Leukocyte count more than 25 × 109/L (13% vs 16%)
- Marked splenomegaly (21% vs 31%)
- Constitutional symptoms (29% vs 34%)
- 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.
The current document should serve as a valuable resource for patients and physicians and provides context for the design and interpretation of clinical trials.
Ayalew Tefferi, M.D., Terra L. Lasho, M.T., Thitina Jimma, M.D., Christy M. Finke, B.S., Naseema Gangat, MBBS, Rakhee Vaidya, MBBS , Kebede Hussein Begna, M.D., Aref Al-Kali, M.D., Rhett P. Ketterling, M.D., Curtis A. Hanson, M.D., Animesh Pardanani, MBBS, Ph.D.