An NCI-designated Comprehensive Cancer Center
By Letisia Marquez | February 2, 2017
Alex Herrera Alex F. Herrera, M.D., assistant professor in City of Hope’s Department of Hematology and Hematopoietic Cell Transplantation

Double-hit lymphomas and double-expressor lymphomas are some of the most difficult non-Hodgkin lymphomas to treat. Patients with these types of lymphomas, which are subtypes of diffuse large B-cell lymphoma, don’t respond as well to chemotherapy treatment as other lymphoma patients do.

An estimated 22,000 patients nationwide are diagnosed with diffuse large B-cell lymphoma each year. About 5 to 10 percent have double-hit lymphoma (or cancer cells that contain chromosomal rearrangements of the MYC, BCL2 and/or BCL6 genes) and about 20 to 30 percent have double-expressor lymphoma (containing the MYC and BCL2 genes).

Which is why Alex F. Herrera, M.D., an assistant professor in City of Hope's Department of Hematology and Hematopoietic Cell Transplantation, and a team of doctors at City of Hope and the Dana-Farber Cancer Institute examined how well patients whose double-hit and/or double-expressor lymphoma had recurred, or was resistant to initial treatment, fared after they had received high-dose chemotherapy and underwent an autologous stem cell transplantation. The transplant utilizes a patient’s own healthy stem cells to help the body recover more quickly from high-dose chemotherapy.

The Journal of Clinical Oncology published the study’s results in its January 2017 issue.

As part of the study, researchers examined the biology of each patient’s tumor. This included an evaluation for chromosomal rearrangements involving the MYC, BCL2 and BCL6 genes, and testing for the presence of those genes as proteins in the lymphoma cells.

In total, they examined the tumor tissue and clinical data of 117 patients at both institutions to determine how these patients fared after receiving high-dose chemotherapy and autologous stem cell transplantation.

The conclusion: Patients with relapsed or treatment-resistant double-hit and/or double-expressor lymphomas didn’t respond as well to the transplantation as diffuse large B-cell lymphoma patients who did not have those types of lymphoma.

In addition, most patients with double-expressor or double-hit lymphoma eventually relapsed, or the cancer returned. Patients with double-hit lymphomas, in particular, had the poorest outcomes.

“This is a high-risk group of patients who should be considered for either a clinical trial to improve the transplant regime or one that introduces a targeted therapy after the transplant to prevent lymphoma recurrence,” Herrera said. “Another possibility would be to consider these patients, particularly patients with double-hit lymphoma, for an allogeneic (donor) stem cell transplant.”

Nevertheless, a significant proportion of patients in the study with double-expressor lymphoma did experience durable remission, or the cancer disappeared for a measurable amount of time, after the transplant; this type of treatment requires further study among these patients, including how the trnsplant process can be improved to make it more effective.

Herrera is also leading research that examines whether patients with these types of lymphomas have better outcomes when they receive a transplant with a donor’s stem cells. (One of Herrera’s studies on this topic was presented at the 2016 annual meeting of the American Society of Hematology. It found that there was no significant difference in how patients with double-hit or double-expressor lymphomas fared after a donor stem cell transplantation compared with patients with diffuse large B-cell lymphoma who did not have those types of lymphoma. Although the findings are preliminary, this may support a role for donor stem cell transplantation in these patients.)

“Double-hit lymphomas and double-expressor lymphomas are two aggressive types of cancers that continue to be challenging to treat, but we are studying excitement treatment combinations to change that,” Herrera said.


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