ALK-positive anaplastic large cell lymphoma (ALCL)

ALK-positive anaplastic large cell lymphoma (ALCL) is found with a biopsy, most often of a swollen lymph node. Sometimes the biopsy is of skin, bone or another site. A pathologist stains the tissue. The cells carry a marker called CD30 and make an active ALK protein. In about 9 in 10 children and teens with this lymphoma, the ALK change is a gene fusion that joins the NPM1 and ALK genes.

Staging shows where the lymphoma has spread. In children it usually includes CT or MRI scans, a PET scan when possible, and checks of the bone marrow. It also checks the fluid around the brain and spinal cord, using a lumbar puncture (spinal tap). The lymphoma reaches the brain or spinal cord only rarely, in about 1 to 3 in 100 children.

In children, a very sensitive blood test (RT-PCR) can find tiny amounts of lymphoma in the blood, called minimal disseminated disease. Doctors may also measure the body’s own antibodies against ALK. Both results help the team judge the risk of relapse.

Treatment follows lymphoma plans made for the person’s age. Adults commonly receive brentuximab vedotin with a chemotherapy combination. Children are treated on pediatric chemotherapy plans. In a U.S. Children’s Oncology Group trial, adding brentuximab vedotin or crizotinib to that chemotherapy prevented relapses during treatment, but crizotinib caused more blood clots than expected.

A transplant is not routinely required in first remission for lower-risk ALK-positive disease. Studies supporting autologous consolidation in other peripheral T-cell lymphomas cannot simply be applied to everyone with ALK-positive ALCL.

Lymphoma that comes back or does not respond may be treated with brentuximab vedotin, chemotherapy or a clinical trial. Since 2021, crizotinib, a medicine that blocks ALK, has been approved in the U.S. for children 1 year and older and young adults in this situation. U.S. transplant guidelines (ASBMT, now ASTCT, 2017) support a transplant with the person’s own cells or with a donor’s for lymphoma that comes back but still responds to treatment. For children, a later international trial found that an own-cell transplant did not work well after an early relapse. In that trial, most children whose lymphoma came back more than a year after diagnosis were still free of it 5 years later after vinblastine alone, and a donor transplant was used for higher-risk relapses.

Most children and teens with ALK-positive ALCL survive. Across many trials with different chemotherapy plans, about 7 in 10 stayed free of relapse or other events after first treatment. Many whose lymphoma returns can still be treated successfully, so overall survival is higher, approaching 95 in 100 in a 2025 review.

In children, several findings point to a higher risk of relapse. They include lymphoma found in the blood at diagnosis or still found early in treatment. Low levels of antibodies against ALK and certain patterns under the microscope also count. If the lymphoma returns, the time since diagnosis matters a great deal. A late relapse, more than a year after diagnosis, often responds to milder treatment. An earlier one needs stronger treatment.

In French-based GELA trials of adults, two factors were linked with lower survival: age 40 or older, and a high level of a blood protein called beta-2 microglobulin. These numbers describe groups, not what will happen to any one person.