Leukemia Drug Kills T-cells, Spares Immunity

A study published this January by dermatologists at Brigham and Women’s Hospital may transform the way physicians approach treatment for leukemic cutaneous T-cell lymphoma (L-CTCL).

L-CTCL is a cancer that affects a type of white blood cell known as the T-cell and causes damage to the skin and other organs. Once diagnosed, patients with the disease generally have a poor prognosis—with an average of three years to live.

BWH Department of Dermatology chairman Thomas S. Kupper and BWH assistant professor of dermatology Rachael A. Clark led a study which explored the efficacy of a new drug regimen to treat L-CTCL. Their report, which was published in Science Translational Medicine, showed that a low dosage of the drug Campath, or alemtuzumab, combats L-CTCL by selectively targeting cancer cells. In addition, they found that the low-dose Campath allows for treatment without increasing their patients’ risk of acquiring infections.

“Standard chemotherapies and alemtuzumab can put L-CTCL into partial or complete remission, but the disease is not curable and eventually will recur,” Kupper wrote in an emailed statement to The Crimson.

Much of Clark and Kupper’s work involved understanding Campath’s interaction with the immune system, specifically T-cells. Though previously believed to kill all T-cells and B-cells—the cells at the frontline of the immune response—the researchers found that Campath actually only kills T-cells that enter the blood stream.

“The amazing thing about Campath is that it kills all the T-cells in the circulation but it doesn’t kill the T-cells in the skin,” said Clark. “They [the T-cells in the skin] are protected from the medication because they don’t circulate.”

Through the course of the study, Clark and Kupper administered Campath to patients with L-CTCL. They found that the patients improved most significantly when given low doses of the drug. In order to study the physiological effects of the drug, the researchers then took blood samples and skin biopsies. Upon examination, they found that T-cells in the skin remained greatly unaffected as the patients improved.

“We sampled their skin through skin biopsies [and] found large numbers of T-cells in the skin,” Clark said. “Here was the drug that was supposed to kill all the T-cells and yet there they were.”

With this finding, Clark and Kupper were led to further investigate the nature of these unaffected skin T-cells. Their research demonstrated for the first time that there were two types of T-cell populations in humans and validated extensive research on the migratory patterns of T-cells within tissues.

“This is still a very novel concept—a sort of paradigm shift in the way we view the immune system—but our work and that of others suggest that we need to pay very close attention to what is happening in tissues,” said Kupper.

With the publication of these ground-breaking findings, the scientists wished to acknowledge the patients who participated in their research.

“The real heroes of this work are our patients, who in spite of this devastating disease willingly and often enthusiastically donated their blood and skin biopsies for this work,” said Kupper.

—Staff writer Fatima Mirza can be reached at fmirza@college.harvard.edu.