Post-essential thrombocythemia myelofibrosis (post-ET MF)

Essential thrombocythemia (ET) is a slow-growing blood cancer in which the bone marrow makes too many platelets, the cells that help blood clot. Many people live with ET for many years. Its care focuses on preventing clots and bleeding: some people are simply watched, while others take low-dose aspirin or medicines such as hydroxyurea, interferon or anagrelide to lower platelets.

In a small number of people, ET slowly changes. Scar-like fibers build up in the marrow, and it can no longer make enough healthy blood. This later stage is called post-ET myelofibrosis. It belongs to the same family, the myeloproliferative neoplasms (MPNs), as primary myelofibrosis.

Some people first told they had ET may actually have had an early (prefibrotic) form of primary myelofibrosis, which can look similar at first. This is one reason reported rates of change vary between studies.

ET is driven by gene changes that happen in a blood-forming stem cell during life. A Japanese nationwide study looked at 163 people found to have post-ET myelofibrosis between 2012 and 2020. Of those tested, about 57% had a JAK2 change, about 24% a CALR change and about 4% an MPL change. These changes are not usually inherited, and the condition cannot be caught from anyone.

Why ET turns into myelofibrosis in some people is not fully known. Studies link a higher chance to older age, a high white-cell count, anemia, early fibers in the marrow, certain gene findings and, in some studies, treatment with anagrelide. Having these features does not mean it will happen.

The change is usually slow. In the Japanese study, people had typically lived with ET or polycythemia vera for about 10 years before myelofibrosis was found. The earlier pattern of high platelets can give way to anemia, falling platelets, a growing spleen, and symptoms such as tiredness, night sweats, weight loss and feeling full quickly.

Low blood counts raise the risk of bleeding and infection. The disease can also turn into acute myeloid leukemia, which was the most common cause of death in the Japanese study.

A bone marrow biopsy confirms the scarring. Doctors then estimate risk. A score made for this condition, MYSEC-PM, uses hemoglobin, blast cells in the blood, platelet count, symptoms, age and whether a CALR gene change is present. Other scores, such as DIPSS-plus, are also used; a 2023 Japanese study found DIPSS-plus predicted survival better than MYSEC-PM among its patients.

Hearing that ET has changed can be hard, especially after years of stable care. The focus often shifts from controlling high platelets to managing anemia, the spleen and symptoms. Care may include more blood tests, transfusions and daily medicine, and stopping a JAK inhibitor suddenly can make symptoms flare.

Most people are older adults by this point; in the Japanese study, the typical (median) age when myelofibrosis was found was 70. Transplant decisions weigh the disease’s risk against the person’s overall health. Older age does not always rule a transplant out: in a large European study, about half of people who had a transplant for myelofibrosis were over 60.

Recovery from a transplant takes months and needs a caregiver. People are watched closely for infections and graft-versus-host disease, and blood tests track the JAK2, CALR or MPL change so an early return can be treated.

A transplant for this condition always uses a donor’s blood-forming cells. A brother or sister with a full HLA match is the first choice when there is one. But in a large European study, only about 1 in 4 transplants for myelofibrosis used a matched sibling. About 6 in 10 used an unrelated volunteer.

In that study, results with a well-matched unrelated donor were similar to those with a matched sibling. Half-matched family (haploidentical) donors and partly matched unrelated donors were also used. Survival was lower on average with them, mainly because more people died of transplant complications, but they give an option to people with no full match.

Most people with ET will never need a donor. For the few whose disease becomes higher-risk myelofibrosis and who can have a transplant, a registry volunteer may make that option possible. No one can promise a match for a particular person.