Study finds no clear benefit of stem-cell transplant for double-hit lymphoma patients in remission

Patients with double hit lymphoma (DHL) who undergo autologous stem-cell transplantation (autoSCT) after achieving remission are not more likely to remain in remission or live longer than patients who do not undergo autoSCT, according to a new analysis from the Perelman School of Medicine and the Abramson Cancer Center of the University of Pennsylvania. The study looked at long term outcomes for patients who achieved remission and, in most cases, found no clear benefit to the transplant, except potentially in patients who received standard front-line chemotherapy, who were less likely to remain in remission than those patients receiving intensive front-line chemotherapy. The findings are published this month in the Journal of Clinical Oncology.

DHL is a form of aggressive B cell non-Hodgkin lymphoma characterized by genetic alterations that drive the lymphoma's growth. This variant is associated with a poor prognosis as compared to other forms of aggressive B cell lymphomas, as patients with this disease survive only an average of two years after diagnosis. Relapses of this disease are almost always fatal, meaning that keeping patients in remission is crucial.

"A major dilemma for oncologists who treat this disease was whether or not to recommend the potentially harmful therapy of autoSCT to patients with this disease a strategy to help keep them in remission," said Daniel J. Landsburg, MD, an assistant professor of Hematology Oncology at Penn and the study's lead author.

Landsburg and his team looked at data on 159 patients from 19 different academic medical centers across the United States. Patients were diagnosed between 2006 and 2015, and all achieved remission following intensive front-line chemotherapy or the standard chemotherapy regimen containing rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Of the total patients, 62 underwent an autoSCT, while 97 did not. Landsburg noted that there were no significant differences between the patient groups at baseline.

"Our result is not explained by differences in patients' overall health or disease features," Landsburg said. "The transplant and non-transplant arms of this study were very well-matched."

Overall, 80 percent of the patients were still in remission three years later, and 87 percent were still alive. When researchers broke the patients into two groups, autoSCT and no autoSCT, they found 89 percent of autoSCT patients were still in remission at three years, as were 75 percent of patients who did not receive an autoSCT. Also at three years, 91 percent of autoSCT patients were still alive, compared to 85 percent of non-autoSCT patients. None of these differences were found to be statistically significant.

"Once these patients achieve remission, the data show they are likely to stay in remission," Landsburg said. "In the absence of a large randomized controlled trial, which would be very challenging to carry out in this case, this is the best evidence we have, and it shows there's no clear benefit to these patients undergoing autoSCT."

Landsburg did point to one exception in the data, and that was in patients who underwent RCHOP, the standard front-line chemotherapy regimen. Just 56 percent of them were still in remission at three years, far lower than patients who received the more intensive front-line therapies.

"Even if patients do go into remission with RCHOP, it appears to be less durable, so in these cases, going forward with autoSCT may still make sense," Landsburg said.

Landsburg says the next step will be to study features of patients who don't go into remission in order to understand why their disease is resistant to therapy and if that can be overcome with different treatment strategies. He says it's also important to try to find more effective therapies for DHL patients who relapse.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.

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