ALK-negative anaplastic large cell lymphoma (ALCL)

ALK-negative anaplastic large cell lymphoma (ALCL) is found with a biopsy, most often of a swollen lymph node. Doctors prefer a lymph node biopsy whenever possible. Taking out a whole node (excisional biopsy) gives a clear answer a little more often than a thin needle sample (core biopsy).

The pathologist, a doctor who diagnoses disease from tissue, uses special stains. In ALCL the cells carry a marker called CD30. In this form, a stain for the ALK protein is negative. Gene tests on the tissue may look for changes called DUSP22 and TP63 rearrangements, which sort ALK-negative ALCL into groups. T-cell lymphomas are rare and easy to misclassify. Experts advise that a pathologist with lymphoma experience review the biopsy.

Next comes staging, to see where the lymphoma is. This often includes a PET-CT scan. A bone marrow biopsy may be added when the result would change the treatment plan, or when blood counts are low.

Brentuximab vedotin targets CD30 and is commonly combined with cyclophosphamide, doxorubicin and prednisone for initial systemic ALCL treatment in adults. Other regimens may be selected according to medical circumstances and access.

After a response, autologous transplantation may be considered for some eligible patients. It allows high-dose chemotherapy followed by return of the person’s own stem cells. U.S. transplant guidelines (ASBMT, now ASTCT, 2017) recommend this step after first treatment. The evidence comes from pooled and retrospective studies and from an exploratory look at the large ECHELON-2 trial, where people in complete remission who had the transplant went longer before the lymphoma got worse. This has not been confirmed in a randomized trial, so the choice is made person by person.

At relapse or with refractory disease, additional drug treatment can be used to achieve control. Allogeneic transplantation may offer a chance of durable remission in selected patients. Its potential immune benefit must be weighed against treatment-related complications and the available non-transplant options.

ALK-negative ALCL is a serious lymphoma, but many people reach remission. In a large trial, adding brentuximab vedotin to first treatment improved survival. The outlook depends on stage, age, general health and how well the lymphoma responds to first treatment. Adults were studied in French-based GELA trials. There, two factors were linked with lower survival: age 40 or older, and a high level of a blood protein called beta-2 microglobulin.

Gene findings in the lymphoma may also matter. TP63 changes have been linked with poorer outcomes. Studies disagree about DUSP22 rearrangements: one found longer control of the lymphoma, another found no difference. For people in complete remission after first treatment, teams often discuss an autologous transplant, using the person’s own stored stem cells. In an exploratory look at a large trial, people who had one stayed free of progression longer. That was not a randomized comparison.

The first figure below comes from people treated mostly with standard chemotherapy. The second comes from a trial that added brentuximab vedotin. Both describe groups, not any one person.