Prognosis

The onset of myelofibrosis may be difficult to date.

Figures for median survival range from 3.5 to 5 years but this may vary with some patients dying within 1 or 2 years after diagnosis while some survive more than 10 years (1).

The Dynamic International Prognostic Scoring System (DIPSS) plus prognostic model for primary myelofibrosis (PMF) has used 8 risk factors to estimate survival from time of diagnosis:

• age > 65 years
• hemoglobin level < 10 g/dL
• leukocyte count > 25 × 109/L
• circulating blasts ≥1%
• presence of constitutional symptoms
  • weight loss > 10% of baseline value in the year preceding diagnosis
  • unexplained fever
  • excessive sweats persisting for > 1 month
• red cell transfusion need - a transfusion-dependent patient automatically has 2 risk factors because of their transfusion need (1 risk point) and hemoglobin level < 10 g/dL (1 risk point)
• platelet count < 100 × 109/L
• unfavorable karyotype (2)

According to the number of risk factors, patients can be categorise as

• low risk - no risk factors, median survival is around 15.4 years
• intermediate 1 risk - one risk factor, median survival around 6.5 years
• intermediate 2 risk - 2 or 3 risk factors, median survival around 2.9 years
• high risk - 4 or more risk factors, median survival 1.3 years (2)

Recognition that unfavorable cytogenetic abnormalities, red blood cell (RBC) transfusion dependence and thrombocytopenia impact prognosis in PMF led to the refinement of the DIPSS into the DIPSS-plus, which adds these three adverse features to DIPSS risk (3)

• 1 point each is assigned to DIPSS intermediate-1 risk,
  • unfavorable karyoptype (defined as complex karyotype, or single or two abnormalities including +8, -7/7q-, i(17q), -5/5q-, 12p-, inv(3) or 11q23 rearrangement), platelets <100 × 109/l, and RBC transfusion need
  • DIPSS intermediate-2 and high risk are assigned 2 and 3 points, respectively
• low (0 points), intermediate-1 (1 point), intermediate-2 (2-3 points) and high (4-6 points) risk patients had median survivals of 180, 80, 35 and 16 months, respectively

Death may result from

• progressive marrow failure
• transformation to acute nonlymphoblastic leukemia
• infection
• thrombohemorrhagic events
• heart failure
• portal hypertension (4)

Myelofibrosis (MF), including primary MF (PMF), post-essential thrombocythemia MF (post-ET/MF), and post-polycythemia MF (post-PV/MF), is a progressive myeloid neoplasm characterized by clonal ineffective hematopoiesis, extramedullary hematopoiesis, a reactive bone marrow environment resulting in reticulin deposition and fibrosis, and a propensity toward leukemic transformation (5)

• compared with ET, PV, and a novel pathological category termed prefibrotic/early PMF, MF carries the poorest prognosis

Reference:

• (1) Cervantes F. Modern management of myelofibrosis. Br J Haematol. 2005;128(5):583-92.
• (2) Tefferi A. How I treat myelofibrosis. Blood. 2011;117(13):3494-504.
• (3) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739355/Bose P, Verstovsek S. Prognosis of Primary Myelofibrosis in the Genomic Era. Clin Lymphoma Myeloma Leuk. 2016;16 Suppl:S105-S113. doi:10.1016/j.clml.2016.02.031
• (4) National Cancer Institute at the National Institutes of Health. Primary Myelofibrosis
• (5)Schieber M, Crispino JD, Stein B. Myelofibrosis in 2019: moving beyond JAK2 inhibition. Blood Cancer J. 2019;9(9):74. Published 2019 Sep 11. doi:10.1038/s41408-019-0236-2