Post-polycythemia vera myelofibrosis (post-PV MF)

Polycythemia vera (PV) is a slow-growing blood cancer in which the bone marrow makes too many red blood cells, and often too many white cells and platelets. Many people live with PV for years. Its care focuses on preventing blood clots, often with regular blood removal (phlebotomy), low-dose aspirin and sometimes medicines such as hydroxyurea, interferon or ruxolitinib.

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

PV is driven by a change in the JAK2 gene that happens in a blood-forming stem cell during life. Almost everyone with post-PV myelofibrosis carries this change. It is not usually inherited and cannot be caught from anyone.

Why PV turns into myelofibrosis in one person and not another is not fully known. Studies link a higher chance to older age, a high white-cell count, a large spleen, early fibers in the marrow and a larger share of blood cells carrying the JAK2 change. Having these features does not mean it will happen.

The change is usually slow. A Japanese nationwide study looked at 272 people found to have myelofibrosis after PV or essential thrombocythemia between 2012 and 2020. They had typically lived with the earlier condition for about 10 years first. Instead of too many red cells, a person may now have anemia, a growing spleen, and symptoms such as tiredness, night sweats, weight loss and feeling full quickly.

Low platelets can cause bruising or bleeding, and low white cells raise the risk of 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 PV has changed can be hard, especially after years of stable care. The focus often shifts from controlling high blood counts 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 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 PV 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.