This unusual blood cancer appears in the skin

When the rash first appeared in 2008, Paul Raffer, MD, thought it was most likely something quite benign. He is a neurologist, not a skin doctor, but he had practiced long enough to know that a rash is a very common symptom in medicine. For several months, he was treated with steroids. The rash would get better, but then it would come back, worse than before.

The rash changed over time, ultimately finding its way to every part of his body. The most troubling symptom, however, was the itching.

"I have never in my life imagined what it would be like to have your whole body constantly itching," Raffer said. "I stopped being able to sleep. My skin started flaking and peeling. It also started getting very thick plaques, with lesions all over my back, my abdomen and my arms. But the worst part was the itchiness. And there was nothing that worked very well to control it."

After a consultation with a dermatology specialist who suspected Raffer might be having an allergic reaction to some substance, Raffer went through a series of tests that disproved that theory. Next, he was directed to a dermatopathologist who did a second look at Raffer's skin and shared the results: mycosis fungoides, sometimes called cutaneous T cell lymphoma of the skin.

Go to Stanford, this physician told Raffer. "See Dr. Youn Kim. If not one of the world's experts, she is certainly the West Coast guru for what you have."

What is mycosis fungoides?

Mycosis fungoides is a type of lymphoma—the most common form of blood cancer. When someone has mycosis fungoides, malignant cells in the blood travel to the skin. The most common mycosis fungoides symptoms causes lesions that appear as a scaly, itchy rash. That rash can ultimately transform into tumors and malignant cells can spread to other organs in the body. Mycosis fungoides, which translates roughly as mushroom-like fungating disease, is the most common form of a subfamily of cancers caused by one particular type of immune system cell, the T-cell lymphocyte.

Youn Kim, MD, director of Stanford's multispecialty cutaneous lymphoma program, quickly discovered that Raffer's mycosis fungoides, which can grow quite slowly, had advanced to an aggressive form called Sézary syndrome. That made Raffer's disease state a Stage 4. That truly frightened him.

"Your insides fall out when you hear Stage 4 of anything," Raffer said. "But I figured if anyone was going to be able to figure out the way to treat this, it would be the team at Stanford." 

What is Sézary Syndrome?

With Sézary Syndrome, the disease has further infiltrated the blood so the cancerous cells circulate continuously and develop leukemia (cancer of the blood). Current therapies work only for four to six months and the cancer cells become more resistant and aggressive after each treatment, Kim said. When she saw him, Raffer already had tumors in his skin.

"We had to address that with aggressive treatment," Kim said. "With patients like Dr. Raffer, you definitely need to think about a permanent change—specifically, a stem cell transplant to replace the immune system with donor cells which would keep the disease permanently in check."

Often, a sibling can make a good cell donor, but Raffer was an adopted child and knew of no siblings.

Plotting a steady course to treat the disease

First, however, Raffer's doctors had to reduce the progression of his disease. "If the donor cells have too much to fight against, then the transplant won't work," Kim said. First came photopheresis, a process in which some of Raffer's blood was removed and its white cells separated out. Those cells were then treated with a drug, radiated, and put back into Raffer. That stabilized the Sézary syndrome activity in his blood, but did not do much for his skin. Next, the Stanford team tried a new monoclonal antibody, attempting to boost the body's own immune system response by directing it at Raffer's cancerous cells but that particular biologic therapy didn't work for Raffer.

The team also tried an approach directed at the skin: Exposing the entire surface of Raffer's skin to electron beam radiation. Sézary syndrome does not typically respond to conventional chemotherapy, so Kim and her colleague Wen-Kai Weng, MD, PhD, an expert in the Blood and Bone Marrow Transplant Program, reached first to biologic or targeted drugs that have proven useful for others. They didn't work for Raffer, however.

One good piece of news did come Raffer's way: A match was found for his blood profile. "That immediately buoyed my spirits," Raffer said. That good news was followed by a downward slide in his condition: Raffer's weakened immune system made him vulnerable to illness. At one point, Weng remembers, "We were in the room with him and his wife, and we're all crying because we can't move forward with the transplant. We were not sure he would make it."

Raffer did not give up.

"I really didn't have any doubt—and Dr. Kim was always very optimistic, even when things went badly."

And badly they did go. Raffer was hospitalized several times with high fevers caused by the very common bacterium, staphylococcus aureus. That was followed by treatment with another medication, one that helped his skin but not his blood. That was followed, finally, by one that did—a delivery of the diphtheria toxin specifically to malignant immune system cells.

Leaving Sézary Syndrome behind

Now Raffer was ready for the stem cell transplant. Using a process developed at Stanford, the team followed a protocol that reduces the destruction of the patient's immune system and encourages a slow but steady negotiation between the patient's immune system and the donor cells that will take over the job of eliminating the cancerous cells. That approach, said Weng, reduces the likelihood that the donor cells will turn against the patient's body.

Raffer, now three years out from the transplant, shows no signs of Sézary syndrome. He's starting to think about going back to work, although part-time only. "I think I have a lot more to give," he said. His doctors still greet him with hugs when he comes for his check-ups. "I learned—not just from Mr. Raffer, but from all our patients— to never give up," Weng said. "Every patient in this program will have a different way to get to transplant."

"We are just so happy for him," Kim said, "and other patients need to know that there is hope. It's not the old days any more. There is a curative route."