Primary plasma cell leukemia

Plasma cells are antibody-making white blood cells that normally live in the bone marrow. In this condition they become cancerous and, unlike in myeloma, they leave the marrow and circulate in the blood in numbers.

"Primary" means it is present at diagnosis rather than developing later out of an existing myeloma. That distinction matters: the secondary form arises in someone who already has myeloma, and the two are counted and studied separately. Primary disease accounts for roughly 60% to 70% of all plasma cell leukemia.

How many circulating plasma cells it takes to make the diagnosis has changed, and it changed recently enough that older material still uses the old number. The original definition required more than 20% of the white cells in the blood to be plasma cells. In 2021 an international working group lowered that to 5% or more.

The reason for the change is worth understanding, because it sounds arbitrary and is not. Two large retrospective studies — one of 482 people, one of 176 — found that people with 5% or more circulating plasma cells had worse survival than people below that line, and that those above 5% and those above 20% did about equally badly. So the higher threshold was excluding people whose disease was behaving the same way.

One consequence is that the condition is now recognised in more people than it used to be. It has been reported at somewhere between 0.5% and 4% of people with myeloma, and the lower threshold has raised that.

The median age in published series runs in the mid to late fifties — younger than the typical age at myeloma diagnosis.

None of the sources we read identifies a cause an individual could have avoided. Nothing here supports a diet, lifestyle, stress or environmental explanation.

What is described is what the cancer cells themselves look like genetically, and they are markedly different from the cells in most myeloma. They frequently carry complex chromosome changes and fewer chromosomes than normal. Several specific chromosome changes associated with higher risk are common, and changes in the TP53 gene — a gene whose normal job is to stop damaged cells dividing — are significantly more common here than in myeloma.

Those are properties of the disease that help explain why it behaves as it does. They are not risk factors, and they are not inherited.

The sources we read do not report on family risk, so we cannot say anything useful about that here.

Because the plasma cells circulate rather than staying in the marrow, this behaves differently from myeloma and it presents differently.

An enlarged liver or spleen is common, as is disease outside the marrow altogether.

The laboratory findings that come with it are kidney failure, a high blood calcium level, low platelets, and raised markers of rapid cell turnover.

It is aggressive, and the sources are direct about that. The review we read describes it as having a poor outlook even with the drugs that work well in myeloma, and the NCI calls the prognosis particularly poor.

We have not put a median survival figure on this page. The published medians run from about 18 months to about 36 months across groups of 23 to 39 people treated in different eras, and on a page someone reads about their own diagnosis a median reads as a countdown rather than as what it is — a midpoint in a small group of other people.

There is no single agreed best regimen, and the review we read says so plainly rather than implying one.

Treatment starts with a combination of drugs aimed at the plasma cells, usually three or four together, drawn from the same families used in myeloma: a proteasome inhibitor, an immune-modulating drug, a steroid, and in some regimens an antibody. Combinations built on bortezomib with lenalidomide and a steroid are described as the preferred induction.

For people fit enough, that is followed by a transplant using their own stem cells — collected in advance, high-dose chemotherapy, then the cells returned to rebuild the marrow. No donor is involved.

Maintenance treatment afterwards appears to matter here. Two retrospective studies found that continuing treatment after the transplant significantly improved how long people went without the disease progressing, or how long they lived.

We have not published response rates for the individual drug combinations. The studies behind them enrolled 14 and 23 people, which is below the threshold this library uses for publishing a percentage, and a response rate is not the same thing as survival.

It moves fast. Unlike myeloma, which is often found through a slow accumulation of back pain, anemia or an odd blood result, this tends to present acutely — kidney failure, a very high calcium level, low platelets — and treatment starts urgently.

People are frequently younger than the typical person diagnosed with myeloma, which changes what the diagnosis interrupts.

Induction runs for months before any transplant, with steroids in nearly every regimen. Then stem cells are collected from the bloodstream through a machine that separates them out, which is an outpatient procedure and a very different day from the admission that follows.

The transplant admission means weeks with very low blood counts, infection risk, and transfusion support. Because the cells are the person’s own, there is no graft-versus-host disease to worry about.

And then treatment usually continues rather than stopping. Maintenance after the transplant is standard practice here, and the disease is managed rather than finished with.

It is rare enough that most people will need a specialist centre, and rare enough that a good deal of what they find online is about myeloma instead.

The transplant used in this disease returns the person’s own cells. No donor, no registry search, no match.

A donor transplant has been studied here, and we are going to report what was found rather than what would suit us.

An earlier registry analysis of 50 people who had a donor transplant found exactly what the theory predicts and exactly the wrong bottom line: fewer relapses than after a transplant using their own cells — 38% against 61% at three years — and worse three-year survival, 39% against 64%, because more people died of the transplant itself.

A later analysis of 71 people found the deaths from the transplant had fallen substantially, from 26% to 9% in the first year. But more people relapsed, and the reduction in deaths did not turn into better survival. Relapse rates, time without progression and overall survival were all no different from a transplant using the person’s own cells.

The review’s own summary is that the outcomes of a donor transplant here are disappointing, that some people do achieve long-term remission, and that it might cure some people — with more study needed, particularly on the preparative treatment used. That is an unresolved question, not a recommendation.

We also checked the main European transplant guidance and this disease does not appear in it at all — searched in full, no mention. There is no published indication to point to in either direction.

So if you have just been given this diagnosis, nobody is starting a donor search on your account. Donors matter enormously for leukemia, for aplastic anemia and for the inherited marrow disorders, and a charity that recruits them should be the first to say when a disease is not one of those.