A Mayo Clinic-led group of researchers has discovered three subgroups of a single type of non-Hodgkin lymphoma that have markedly different survival rates. These subgroups could not be differentiated by routine pathology but only with the aid of novel genetic tests, which the research team recommends giving to all patients with ALK-negative anaplastic large-cell lymphoma (ALCL). Findings are published in the journal Blood.
Patients whose lymphomas had TP63 rearrangements had only a 17 percent chance of living five years beyond diagnosis, compared to 90 percent of patients whose tumors had DUSP22 rearrangements. A third group of tumors, those with neither rearrangement, was associated with an intermediate survival rate.
“This is the first study to demonstrate unequivocal genetic and clinical heterogeneity among systemic ALK-negative anaplastic large-cell lymphomas,” says Andrew L. Feldman, M.D., a Mayo Clinic pathologist and senior author on the multi-institutional study. “Most strikingly, patients with DUSP22-rearranged ALCL had excellent overall survival rates, while patients with TP63-rearranged ALCL had dismal outcomes and nearly always failed standard therapy.” Dr. Feldman also is a Damon Runyon Clinical Investigator.
ALCL is a rare type of non-Hodgkin lymphoma, but one of the more common subtypes of T-cell lymphoma, according to the Lymphoma Research Foundation. ALCL comprises about three percent of all non-Hodgkin lymphoma and 10 to 30 percent of all cases in children. Currently, all ALK-negative anaplastic large-cell lymphomas are treated the same, using chemotherapy and, in some institutions, stem cell transplantation. Results from the study make a clear case for additional testing and possible changes standard of care.
“This is a great example of where individualized medicine can make a difference,” says Dr. Feldman. “Patients whose chance of surviving is 1 in 6 are receiving the same therapy as patients whose odds are 9 in 10. Developing tests that identify how tumors are different is a critical step toward being able to tailor therapy to each individual patient.”
TP63 and DUSP22 rearrangements are examples of abnormal swapping of DNA that disturbs the way genes are arranged on a tumor cell’s chromosomes. These abnormalities cannot be seen in the standard microscopic evaluation that pathologists use to diagnose lymphoma, but can be visualized using a genetic test called fluorescence in situ hybridization (FISH). The authors of the study recommend performing FISH in all patients with ALK-negative anaplastic large-cell lymphoma. Learn more about the new tests:
Other authors include Edgardo Parrilla Castellar, M.D.; Ph.D., Rhett Ketterling, M.D.; Ryan Knudson, Liuyan Jiang, M.D.; Karen Grogg, M.D.; Cristine Allmer; Kay Ristow; George Vasmatzis, Ph.D.; William Macon, M.D.; Mark Law; James Cerhan, M.D., Ph.D.; Thomas Habermann, M.D.; Stephen Ansell, M.D., Ph.D.; Ahmet Dogan, M.D., Ph.D.; and Matthew Maurer, all of Mayo Clinic; Elaine Jaffe, M.D.; Alina Nicolae, M.D., Ph.D.; Wyndham Wilson, M.D.; all of National Cancer Institute; Jonathan Said, M.D. of UCLA, Steven Swerdlow, M.D.; Sarah Gibson, M.D., of University of Pittsburg; Jagmohan Sidhu, M.D., of United Health Services Hospitals; Eric Hsi, M.D.; Sarah Ondrejka, D.O., all of Cleveland Clinic; Shridevi Karikehalli, M.D. of Centrex Clinical Laboratories.
The research was supported by the Mayo Clinic Center for Individualized MedicineBiomarker Discovery Program and the Department of Laboratory Medicine and Pathology at Mayo Clinic, the University of Iowa/Mayo Clinic Lymphoma SPORE and other funding from the National Cancer Institute, and the Damon Runyon Cancer Research Foundation.