Primary myelofibrosis (PMF)

Blood cells are made in the bone marrow, the soft tissue inside bones. In primary myelofibrosis, a blood-forming stem cell picks up a change and makes too many abnormal cells. Over time, scar-like fibers build up in the marrow, and it becomes harder for the marrow to make healthy blood.

When the marrow struggles, blood-making can move to the spleen and liver, which then swell. Primary myelofibrosis is one of the myeloproliferative neoplasms (MPNs), a family of blood cancers that also includes polycythemia vera and essential thrombocythemia. “Primary” means it did not grow out of one of those earlier conditions.

Doctors now separate an early “prefibrotic” stage, with little scarring, from the “overt” stage with clear scarring. The early stage can look like essential thrombocythemia, so the marrow biopsy matters.

It is caused by gene changes that happen in a blood-forming stem cell during a person’s life. The most common is a change in the JAK2 gene, found in about 6 in 10 people. Changes in the CALR or MPL genes explain many of the rest, and a small group has none of the three.

These changes are not inherited from a parent, and a person with the disease does not pass them to their children. Now and then more than one person in a family has one of these blood cancers, but that is uncommon. The condition is not an infection and cannot be caught from anyone. Why the first change happens in a given person is usually unknown.

Other gene changes found in the marrow help doctors judge how fast the disease may move. For example, some changes in genes such as ASXL1 or SRSF2 are linked to a harder course.

It often causes no symptoms early on, and about a third of people have none when it is found. When symptoms come, they can include tiredness and shortness of breath. A large spleen can cause pain or fullness under the left ribs, or feeling full after a few bites. Bone pain, fever, heavy night sweats and weight loss can also happen.

Low red cells cause anemia. Low platelets can cause bruising or bleeding, and low white cells raise the risk of infection. In some people the disease turns into acute myeloid leukemia, which is much harder to treat.

Diagnosis uses a blood count, a bone marrow biopsy, and tests for chromosome and gene changes. Doctors then use a risk score, such as DIPSS, DIPSS-plus or MIPSS70, to estimate how the disease may behave. These scores combine things like age, hemoglobin, symptoms, blast cells in the blood and gene results.

Many people live with fatigue, night sweats and the discomfort of a large spleen. Care often means regular blood tests, clinic visits and, for some, frequent transfusions. Stopping a JAK inhibitor suddenly can make symptoms flare, so any change is planned with the care team.

Deciding about a transplant is hard. The team weighs the risk of the disease against the risk of the transplant, and looks at other health problems, overall fitness and the size of the spleen. 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. Blood counts need time to recover, and people need a caregiver, close follow-up, and care for infections and graft-versus-host disease. Some people also need more than one treatment if the disease comes back.

A transplant for myelofibrosis always uses a donor’s blood-forming cells. A brother or sister with a full HLA match is still the first choice when there is one. But most patients are older adults. In a large European study, only about 1 in 4 transplants used a matched sibling, while 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. Partly matched unrelated donors and half-matched family (haploidentical) 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.

Not everyone with myelofibrosis will need a donor, and joining a registry cannot promise a match for a particular person. But for people who need a transplant and have no matched brother or sister, a well-matched volunteer can make that option possible.