Primary plasma cell leukemia (pPCL)

Primary plasma cell leukemia is found with the same tests used for multiple myeloma. Blood and urine tests measure the abnormal antibody that myeloma cells make. Other blood tests check blood counts and levels of substances such as calcium. A bone marrow biopsy shows how many abnormal plasma cells are in the marrow. Imaging such as MRI, CT or PET scans looks for bone damage.

The key step is a close look at the blood itself. Since 2021, the International Myeloma Working Group (IMWG) has defined primary plasma cell leukemia as 5% or more plasma cells on a blood smear (circulating plasma cells) in someone who otherwise meets the criteria for active myeloma. The older rule, from 1974, required more than 20% plasma cells and a high total count of them in the blood. The IMWG recommends a careful smear review for everyone with myeloma, with at least 100 to 200 cells counted by an experienced specialist. Some labs also use flow cytometry, a test that sorts cells by markers on their surface. It can pick up more of these cells than a microscope count.

Gene tests on the cancer cells (cytogenetics and FISH) are also part of the workup. Compared with typical myeloma, plasma cell leukemia more often carries changes called t(11;14), t(14;16), del(17p) and extra copies of part of chromosome 1 (1q gain). Blood tests often show high LDH and beta-2 microglobulin. These reflect a large and fast-growing amount of cancer.

Treatment usually combines modern myeloma medicines: a proteasome inhibitor (such as bortezomib or carfilzomib), an immunomodulatory drug (such as lenalidomide), a steroid and often an anti-CD38 antibody (daratumumab). The plan depends on fitness, kidney and other organ function, and whether a clinical trial is open.

People who are fit enough usually go on to high-dose chemotherapy followed by a return of their own stem cells (an autologous transplant). Some have a second transplant soon after the first: either another with their own cells, or one from a donor (allogeneic).

No randomized trial has shown which transplant plan is best for everyone. In the largest study, a donor transplant given first led to fewer relapses but many more deaths from complications, especially in the first 100 days. Ongoing (maintenance) treatment usually follows, because the disease often comes back. At relapse, options include other medicine combinations, venetoclax for people whose cancer cells carry t(11;14), and CAR-T or bispecific antibodies, though experience with these in plasma cell leukemia is still small.

Primary plasma cell leukemia is the most aggressive of the plasma cell cancers, and experts still call it an unmet need. Survival has improved as newer myeloma medicines and transplants came into wider use. A 2025 European Myeloma Network review reports that people who cannot have a transplant may live a median of up to 2 years on combinations of newer medicines. For people who have a transplant, it is 3 years or more.

Several things shape the outlook. Age matters: in the Netherlands, people 65 and younger lived much longer than older people. Some gene changes, such as del(17p), point to a harder course, while t(11;14) is linked with a better one. A high LDH, low platelets and a very high plasma cell count in the blood also weigh in. In the largest study of transplants for this disease, how well the cancer had responded before the first transplant affected results.

The disease often comes back (relapse). In the European EMN12 trial, treatment went on after transplant with maintenance medicine. For relapse, newer immune treatments such as CAR-T cell therapy have been tried, but experience in plasma cell leukemia is still small. None of these numbers can say how any one person will do.