Leukemia returns even after aggressive treatment in children

Acute lymphoblastic leukemia (ALL) has improved for children over the past few decades. The five-year survival rate for those under 15 is about 90%, but the disease can still return even after aggressive treatment. Researchers at Roswell Park are studying why this happens and how to stop it.

A difficult diagnosis

Hannah Koepsell was 11 when she was diagnosed in June 2022. Instead of finishing her softball season, she spent 39 days in the hospital. Her treatment stretched for two years, including long hospital stays and infections that kept her away from her brother and friends.

She finished chemotherapy in 2024, but five months later, the leukemia returned. She then underwent a bone marrow transplant using cells from her younger brother, who was a 100% match. The cancer returned again in fall 2025, and Hannah received CAR-T cell therapy.

“They actually took out her blood, filtered it out and genetically altered it to kill off the cancer that she had,” her father, Jason Koepsell, said.

Hannah has been in remission since December 2025. Her father was diagnosed with Hodgkin lymphoma at 17 and has been in remission for more than two decades. He said seeing his daughter go through the same disease was difficult.

Why the disease returns

Leukemia is not a single disease but a group of cancers with different genetic features. This means it does not behave the same way in every patient. Infants under 12 months are in a higher-risk group because their leukemia can resist standard chemotherapy.

Even if a patient reaches remission, the cancer cells can change and outsmart therapies. Dr. Lisa Niswander, a pediatric oncologist and physician-scientist at Roswell Park, studies targeted and immune-based approaches for high-risk leukemias.

“The leukemia sort of develops changes that outsmarts our therapies, and the leukemia comes back,” Niswander said.

Once the disease returns, it is harder to treat because the remaining cells are the ones earlier therapies could not eliminate.

Targeted drugs and immune approaches

Niswander’s lab is studying whether pairing CAR-T cells with targeted drugs can attack leukemia in more than one way. This makes it harder for cancer cells to develop resistance. One genetic change seen in some childhood leukemias is a KMT2A rearrangement. In this change, the KMT2A gene breaks and joins with part of another gene. This drives leukemia cells to grow.

Drugs called menin inhibitors can target leukemia cells with certain KMT2A changes. These drugs are being studied and used in both ALL and acute myeloid leukemia. Niswander’s team is looking at how these drugs interact with CAR-T cells. Because CAR-T cells are living immune cells, adding another drug is more complicated than combining two cancer medications.

Researchers first need to know what the second drug does to the CAR-T cells themselves. “Is it good? Is it bad? And how can we most appropriately sort of sequence these medications together to benefit the patients in the long term?” Niswander said. Her team is doing preclinical research, or lab studies, on those interactions. This is the step that comes before combinations can be tested more broadly in patients.

Future directions and care

Some of the chemotherapy drugs Jason received as a teenager were similar to those Hannah later received. He said newer technologies have expanded what is possible. “Seeing the advances that have come out in cancer oncology in general,” he said, “that’s a huge benefit.”

Because treatment affected her immune system, Hannah still receives intravenous immunoglobulin infusions every eight weeks. She also takes a targeted medication matched to the genetic features of her leukemia. Her family said both may continue long term. After long stretches away from school, she is finally getting ready to return to the classroom once again for her 10th grade.