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Can Myelofibrosis Be Reversed?

sMyelofibrosis is classified under myeloproliferative neoplasms and several disorders such as primary myelofibrosis (PMF), polycythemia vera (PV), essential thrombocythemia (ET) (PV and ET were classified as secondary myelofibrosis earlier) comes under this category according to the recent Who classification. Reversal of myelofibrosis is a very controversial topic, there is still no definitive conclusion among scientist if any of the newer drugs really reverse myelofibrosis (MF) or not.

The identification of JAK-2 mutation and the development of JAK-1/JAK-2 inhibitors (drugs) are greatest achievements in myelofibrosis, although only ruxolitinib is approved in the USA and Europe for the treatment of myelofibrosis there are many other JAK-1/2 inhibitors identified and some drugs are still on the experimental level and there are many ongoing clinical trials about these drugs.

Can Myelofibrosis Be Reversed?

Can Myelofibrosis Be Reversed?

There are few case studies/research studies of reversal of myelofibrosis with certain drugs but whether these drugs actually reverse the condition, cure the condition is still debatable. The adverse effects after taking these drugs for a long time also remain unsolved. Some studies state that early myelofibrosis can be reversed with JAK-1/2 inhibitors and even probably with hydroxyurea.(1)

I will present a few case studies found in the literature about the reversal of myelofibrosis but whether these drugs actually reversed the condition is debatable.

This is a case of a 74-years-old elderly male diagnosed with myelofibrosis, due to polycythemia vera (PV). The patient was started on ruxolitinib and a significant reduction in spleen size was observed. Then the dose was reduced because of thrombocytopenia and the splenomegaly was settled completely with this dose. He has a fibrosis score of 3 (according to WHO classification) at baseline and after 168 weeks of treatment, the fibrosis was absent and normal bone marrow cells were present. However, there were severe side-effects present with the drug.

This is another case of a 52-years old male with a diagnosis of myelofibrosis due to PV with an IPSS (prognostic score) intermediate-2 risk level. Fibrosis score was 3 at the baseline and ruxolitinib was started (larger dose than the first case) and he tolerated it well. The constitutional symptoms and splenomegaly were resolved significantly after 4 weeks. After 50 weeks of treatment, there was no splenomegaly and after 17 months of treatment a bone marrow biopsy was done which showed completely solved fibrosis.

There are several analytical studies in the literature showing that JAK-1/2 inhibitors do not reverse myelofibrosis but it significantly improves the symptoms and quality of life. So, the matter remains debatable.

This is a case of a 50 years-old male who was diagnosed with primary myelofibrosis; he already had a splenectomy due to a traumatic incident a few years back and hypertension at the presentation. He was started on anagrelide (hydroxyurea). His platelets dropped in 4 months’ time and he was on anagrelide for 6 years. Then he developed a stroke 6 years after and anagrelide was stopped but after that the platelets were high, WBC was low and a wild type JAK2 mutation was also seen, therefore, anagrelide was restarted and his blood cells came to normal levels. Then few months after he developed pancytopenia so, anagrelide was stopped then a bone marrow biopsy was done which revealed a normal bone marrow and a significant reduction in fibrosis. Since the patient was referred to another state further follow-up was not done.(2)

A study was done recruiting 22 diagnosed patients with myelofibrosis using imetelstat which is still an investigational drug. This drug has a mechanism of action by inhibiting the telomerase activity of the tumor cells which causes tumor cell death. These patients were given this drug and followed-up for 6 months. Out of the 22 patients, 4 patients had a complete remission stage where the bone marrow was normal. However, some patients had bone marrow suppression with this drug so it’s debatable if remission of the myelofibrosis is a toxic event of the drug or not. Also, the 3 of the 4 patients were in an early stage of myelofibrosis therefore, these patients must have gone into a remission stage. Whether imetelstat actually causes remission or not is impossible to say at this stage.


There isn’t any confirmed literature on JAK-1/2 inhibitors, hydroxyurea, and investigational drug imetelstat, whether these drugs actually reverse or cure myelofibrosis. Some studies state that early stages of myelofibrosis can be reversed with the above-mentioned but the toxicity level and long-term side effects of these drugs are still unknown. So, further studies are needed to confirm this matter.


Also Read:

Pramod Kerkar, M.D., FFARCSI, DA
Pramod Kerkar, M.D., FFARCSI, DA
Written, Edited or Reviewed By: Pramod Kerkar, M.D., FFARCSI, DA Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:August 2, 2021

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