B/myeloid mixed-phenotype acute leukemia (MPAL)

Tests usually start with a physical exam, a complete blood count (CBC) and other blood tests. The care team then takes a small sample of bone marrow (a bone marrow aspiration and biopsy). A spinal tap (lumbar puncture) checks the spinal fluid, and an x-ray may be done.

The key test is flow cytometry, a lab method that reads the markers on and inside the leukemia cells. For B/myeloid MPAL, the lab looks for B-cell markers such as CD19, CD79a, CD22 or CD10. It also looks for myeloid features, such as the enzyme MPO or signs of monocyte-type cells. Labs judge how strongly each marker shows up compared with normal cells in the same sample. That is why expert blood pathologists (hematopathologists) read the results.

Chromosome and gene tests on the marrow look for changes such as BCR::ABL1, KMT2A or ZNF384. If one is found, the leukemia's name includes that change, and for BCR::ABL1 a targeted pill is added. These results also shape the risk estimate, so the final diagnosis rests on several reports read together.

No controlled trials have compared treatments for MPAL, so plans rest on careful studies of past patients. Several of these, including a large international study in children, found better results when first treatment followed an ALL-type plan rather than an AML-type plan. Some patients still receive AML-type or combined plans, and the best choice for each situation is still being studied.

Doctors test for measurable residual disease (MRD), the tiny amount of leukemia that only very sensitive tests can find, to judge the response. For adults, experts have commonly advised an allogeneic transplant in first remission when a suitable donor is available and the person is well enough. In children, the large international study, which included all leukemias of mixed or unclear type and not only B/myeloid MPAL, found that transplant in first remission did not improve results overall, with a possible exception for children who still had clear signs of leukemia in the marrow (5% or more blasts) after the first month of treatment.

A transplant replaces the blood-forming system and adds a donor immune attack on leftover leukemia, but it cannot guarantee the leukemia will not return. In a European registry study of 195 adults transplanted in first remission from 2014 to 2023, relapse was more common than death from transplant complications, and the type of conditioning and graft affected results. Newer medicines used in ALL or AML are being tested in MPAL, often through clinical trials.

When a transplant from a donor is planned, the team usually tests brothers and sisters first. Each full sibling has about a one in four chance of being a full match.

Most patients do not have a matched relative. In the words of NMDP, the U.S. registry, “75% of patients don’t have a fully matched donor in their own family.” The team then searches registries of volunteer donors around the world and banks of donated cord blood. In some transplants, a half-matched parent, child or sibling can also be the donor.

Matching depends on inherited tissue markers called HLA, so a patient is most likely to match someone who shares their ancestry. Every person who joins makes the search a little more likely to succeed, especially for patients from groups that are underrepresented on registries.

MPAL is rare, and experts are still learning how best to treat it. The outlook depends on age, the gene changes in the leukemia cells and how well the leukemia responds to treatment. MRD tests, described above, help show that response. In one U.S. study of children with B/myeloid MPAL, a negative MRD test at the end of the first phase of treatment was the strongest sign of doing well.

Children tend to do better than adults. In a large international study, about 8 in 10 children whose first treatment followed an ALL-type plan were alive five years later with no relapse or other major setback. A U.S. registry study of people of all ages found MPAL had a worse outlook than ALL or AML, especially in older people. Results improved between the early and later years of that study. For adults, expert reviews usually advise an ALL-type first treatment followed by a donor transplant in first remission.