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 commonly uses combinations drawn from modern myeloma therapy, including a proteasome inhibitor, an immunomodulatory medicine, a steroid and often an anti-CD38 antibody. Fitness, organ function and trial availability guide the plan.

Eligible patients may proceed to high-dose chemotherapy and autologous stem cell rescue after initial treatment. Tandem approaches, in which a second transplant follows the first, have been studied. These may involve two autologous transplants or an autologous followed by an allogeneic transplant.

No randomized evidence establishes one transplant sequence for every patient with primary plasma cell leukemia. Allogeneic treatment may reduce some relapse risks but adds substantial treatment-related risk. Maintenance or further systemic therapy is often part of planning because relapse remains a concern.

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.