Is Myelofibrosis A Death Sentence?

Myelofibrosis is a neoplastic clonal disorder of the hematopoietic stem cells. It is characterized by bone marrow fibrosis, extramedullary hematopoiesis, anemia, splenomegaly, hepatomegaly and increased number of circulating blast cells. It can either be primary with no known etiology or secondary due to polycythemia vera and essential thrombocytosis. Although, the median time of survival for myelofibrosis patients is 5 years, there are varied rates of survival in individual patients ranging from a year in some high risk patients to over 10 years in low risk patients.

Is Myelofibrosis A Death Sentence?

Myelofibrosis can be a death sentence for patients with high risk and greater disease severity, but not for asymptomatic and low risk patients. The disease being quite rare, in addition to varied outcomes, the disease risk should be considered based on individual basis, severity of symptoms and other factors that might affect the disease outcome. This necessitates increased need for identifying patients who are at a greater risk for poor outcome and treat them accordingly with allogeneic stem cell transplantation.

The only curative treatment for myelofibrosis is allogeneic stem cell transplantation; however, it is associated with high treatment related mortality that touches about 34%. Since, the disease mostly presents in elderly patients, who are at a greater risk of mortality associated with allogeneic stem cell transplantation and contraindication of it for these patients, most myelofibrosis sufferers are refrained from getting stem cell transplantation.

Earlier the prognosis scores were based on two factors, hemoglobin (<10 g/dl) and leucocytes (>30 x 109/l). However, this prognostic system failed to identify higher risk patients in younger age group who could be managed with allogeneic stem cell transplantation. The shortcoming in this scoring system led to a relatively new and superior prognostic scoring system that considered five factors to calculate the severity of disease. These include, age >65 years, hemoglobin <10 g/dl, leucocytes >25 x 109/l, circulating blasts ≥1% and constitutional symptoms. This prognostic scoring system, which had a median survival of 23 months for high risk group applicable at the time of diagnosis, was inferior in identifying patients with very high risk of disease outcome.

In a study of 370 patients, the median survival of ≤12 months was seen in patients with the characteristics of platelets <50 x 109/l, blasts cells in peripheral blood or bone marrow ≥10% and abnormalities in chromosome 17. The added advantage of this study was that, the prognosis was effective not only during initial diagnosis, but also at the time of follow up; therefore, it was easier to determine the survival rate of patients with changing disease scenario. There was increased risk of death if the platelets were below 50 x 109/l and ≥10% blast cells in circulation. In addition, anemia was associated with poorer prognosis with reduced survival and transformation into acute myeloid leukemia. (1) (2)

Although, chromosome 17 abnormality is extremely rare and found only in 2% patients, it carries very poor prognosis with median survival of only 6 months and higher risk (>40%) of transformation into leukemia. The poor prognosis related to chromosome 17 abnormalities is associated with resistance to treatment in other diseases, such as multiple myeloma, chronic lymphocytic leukemia and non-Hodgkin’s lymphoma.

Therefore, it is very important to identify higher risk patients, especially those who are younger and befitted for more aggressive therapy, such as allogeneic stem cell transplantation. Allogeneic stem cell transplantation has proved to be really curative in younger patients with greater disease free remission time. Another medication ruxolitinib (Jakafi), which is JAK1/JAK2 inhibitor is the only FDA approved medication, has shown superior results in modifying the disease course of myelofibrosis patients who have poor prognosis. Other chemotherapeutic agents used in the management of myelofibrosis include interferon, cladribine, hydroxyurea, androgens, corticosteroids, thalidomide, and lenalidomide. Splenectomy is reserved for specific patients who fail to respond to chemotherapy and develop complications such as portal hypertension, progressive anemia, severe thrombocytopenia and persistent splenomegaly. Treatment should always be done under the guidance of an experienced hematologist. (3)

References:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979081/
  2. Tam CS, Kantarjian H, Cortes J, et al. Dynamic model for predicting death within 12 months in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. J Clin Oncol. 2009;27(33):5587–5593. doi:10.1200/JCO.2009.22.8833

    https://www.ncbi.nlm.nih.gov/pubmed/19786661

  3. https://emedicine.medscape.com/article/197954-treatment#showall

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