Myelodysplastic neoplasm with increased blasts

Bone marrow is the tissue inside bones that makes blood. In a myelodysplastic neoplasm the marrow keeps working — often working hard — but the cells it produces are faulty and half-finished, and most of them are destroyed in the marrow or shortly after reaching the bloodstream. The result is a busy factory and an empty blood count.

“Dysplasia” is the word for how those cells look down a microscope: misshapen and immature. It describes appearance, not danger.

The 2022 WHO classification renamed these from “myelodysplastic syndromes” to “myelodysplastic neoplasms”. The abbreviation MDS did not change. The rename matters, because a neoplasm is a cancer in its own right — these are not a waiting room for one.

What sets this subtype apart is the blast count. Blasts are the youngest, most immature blood cells, and a small number is normal. Here they are raised: between 5% and 9% in one form, and between 10% and 19% in the other. That number is one of the main things a risk score is built from, and it is why this subtype usually lands in a higher band than the low-blast ones.

The underlying event is a change acquired in a single blood-forming stem cell during a person’s life. It is not inherited from a parent and it cannot be passed to anyone.

For most people no cause is ever identified. That is the most important sentence in this section, and it comes first for a reason — people look hard for something they could have done differently.

Recognised risk factors do exist: previous chemotherapy or radiotherapy for another cancer, exposure to tobacco smoke, pesticides, and solvents such as benzene, some heavy metals, and increasing age. Age is the dominant one.

Nothing in the sources we read supports a lifestyle, diet, stress or emotional cause.

The immediate harm is a shortage of working blood cells. Too few red cells brings fatigue, breathlessness and pallor. Too few neutrophils brings repeated or severe infections. Too few platelets brings easy bruising, bleeding, and pinpoint red spots under the skin.

There are two separate dangers here and it helps to keep them apart. One is the shortage itself, which can be disabling or dangerous on its own. The other is transformation into acute myeloid leukemia. Many people are harmed by the first without ever reaching the second.

That transformation is conventionally marked at 20% blasts — the youngest, most immature cells in the marrow. It is a classification boundary rather than a moment a person feels.

A higher blast count sits closer to the 20% boundary, and that proximity is most of why this subtype is generally scored as higher risk and treated more urgently than the low-blast forms.

For higher-risk disease the main drug treatments are the hypomethylating agents, azacitidine and decitabine. They work by stripping chemical “off switches” from the DNA of the abnormal cells, letting suppressed genes work again. They are described as first-line for people with higher-risk MDS who are not fit for a transplant.

The two are not interchangeable, and it is worth knowing which one is being discussed. For azacitidine in higher-risk disease the NCI reports median overall survival of 24 months against 16, and two-year survival of 51% against 26%. Two randomised trials of decitabine against supportive care did not show a survival benefit.

Neither is curative. Describing them as controlling or holding the disease is accurate; describing them as beating it is not.

A transplant using someone else’s blood-forming cells is described by the NCI as the only potentially curative treatment for MDS. The EBMT Handbook’s wording is worth having in full: it is the treatment of choice for all patients with higher-risk MDS who are fit enough to be considered for it. Both halves of that sentence carry weight.

Where a transplant is indicated, doing it upfront is preferred. Where that is not possible for practical reasons, hypomethylating agents are usually used to hold the disease in the meantime. Interestingly, lowering the risk score with treatment beforehand has not translated into better outcomes, and blast levels that are raised but stable over time are not in themselves a reason not to transplant.

Clinical trials are a standard option here rather than a last resort.

Most people meeting this diagnosis are in their seventies, and that shapes almost everything about it. The question is rarely only what the disease is doing — it is what a person’s body can withstand alongside it.

Before treatment and often during it, life is organised around blood counts and transfusion appointments. Fatigue is the symptom people most consistently describe and the one most consistently underestimated by everyone else.

If a transplant is on the table there is usually a period of drug treatment while it is arranged, and a genuine decision to make about whether to have one at all. That decision weighs a serious, months-long treatment with real mortality against a disease that is already causing harm — and there is no version of it that is obviously right.

Being told a transplant is not suitable is not the same as being told nothing can be done. Hypomethylating agents, transfusion support and trials are all active treatment.

For people whose disease scores as high or very high risk, EBMT grades a transplant as standard of care — and grades it identically from a matched sibling, a well-matched unrelated donor, and a mismatched alternative donor. An unrelated donor is not second best here.

Both the EBMT Handbook and the practice recommendations treat matched unrelated donors and matched siblings as suitable options in MDS. Half-matched family donors have shown promising results without quite reaching the outcomes of matched donors, and cord blood is used less often because of the cell numbers and slow recovery.

The caveat that keeps this honest: EBMT grades intermediate-risk disease without additional adverse features as “developmental” — meaning further trials are needed — for every donor type. Having increased blasts does not automatically place someone in the band where transplant is recommended.

And the caveat the evidence audit insisted on for MDS generally: a high unrelated-donor share among people who received transplants says nothing about how many people diagnosed with MDS need one. Many are older or have other conditions that rule out intensive treatment.