Therapy-related AML and MDS (t-AML, t-MDS)

Blood cells are made in the bone marrow, the soft tissue inside bones. Therapy-related AML and MDS start there, in the cells that make red cells, platelets and several kinds of white cells. AML (acute myeloid leukemia) is a fast-growing cancer of these cells. MDS (myelodysplastic syndrome) means the marrow makes too few healthy blood cells, and it can turn into AML.

“Therapy-related” means the cancer appeared after earlier chemotherapy or radiation. The World Health Organization (WHO) now calls this group “myeloid neoplasms post cytotoxic therapy.” Doctors often shorten it to t-MN, t-AML or t-MDS. The label describes a person’s medical history, so the report also names the exact type of AML or MDS, which helps guide treatment.

In published studies, it makes up about 5 to 15 in every 100 new diagnoses of AML, MDS and a related condition called CMML.

Many cancer treatments work by damaging the DNA of fast-growing cancer cells. They can also harm the DNA of healthy blood-forming cells. The treatments most strongly linked to therapy-related AML and MDS are chemotherapy drugs called alkylating agents and topoisomerase II inhibitors, and radiation to large areas of the body. In 2022, the WHO added PARP inhibitors, newer medicines used for some breast, ovarian and prostate cancers, to this list.

The timing varies. After alkylating agents, it has typically appeared about 5 to 7 years later. After topoisomerase II inhibitors, it tends to come sooner, often within 1 to 3 years.

Having this cancer does not mean the earlier treatment was a mistake, or that anyone did anything wrong. Those treatments were given to treat a serious illness, and only a small number of people who receive them go on to develop t-MN. Researchers now think that in some people, a small group of changed blood cells was already there before treatment, and the treatment gave those cells room to grow. Some people also carry an inherited gene change that makes them more likely to develop it. It is not contagious.

Like other AML and MDS, it crowds out healthy blood-making. People may feel weak and look pale from anemia, which means too few red cells. Low platelets can cause bleeding, and low white cells can lead to fevers and infections.

Therapy-related AML and MDS are often harder to treat than AML or MDS that appear on their own. They more often carry high-risk changes, such as changes in the TP53 gene or several chromosome changes at once. These findings help doctors judge how the disease may behave.

The care team looks at the first illness and how it was treated, because that can affect which treatments are safest.

Hearing about a second cancer after getting through the first can be very hard. It is natural to feel anger, grief or worry. It can help to ask the care team to explain how the new diagnosis connects to earlier treatment, and to bring someone along to appointments.

The first cancer and its treatment matter when planning what comes next. For example, in a large European study, people who had been treated for lymphoma or chronic lymphocytic leukemia had a higher risk of dying from transplant complications than people treated for breast cancer.

Things can move quickly. In that same study, the middle time from diagnosis to transplant was about 6 months. Recovery from a donor transplant then takes many months, with close follow-up for infections, graft-versus-host disease (when donor immune cells attack the body) and the return of the leukemia.

The transplant used for therapy-related AML and MDS is a donor (allogeneic) transplant. A donor’s blood-forming cells replace the damaged marrow, and the donor’s immune cells can help attack leukemia cells that remain. In AML, the preferred donor is a well-matched brother or sister or a well-matched unrelated volunteer.

Unrelated volunteers play a big part. In a large European study of adults transplanted for this condition, about 7 in 10 received cells from an unrelated donor. There is also a family reason: some people with t-MN carry an inherited gene change. When that is suspected, a relative may be tested for the same change before being chosen as a donor. Cells that carry such a change can cause problems, including a new leukemia that grows from the donor’s cells.

Not everyone with therapy-related AML or MDS will need a donor, and joining a registry cannot promise a match for any one person. But for people who need a transplant and have no suitable relative, a volunteer on a registry can make that option possible.