The death last week of Paul Allen just two weeks after announcing that his non-Hodgkin lymphoma had returned took many by surprise. The Microsoft co-founder and Seattle impresario had sounded optimistic about beating his third cancer diagnosis, which came more than 35 years after he first was diagnosed with Hodgkin lymphoma.
Lymphomas are blood cancers of the lymphocytes, immune cells that fight infection. The two primary types are Hodgkin lymphoma and non-Hodgkin lymphoma, both named after Dr. Thomas Hodgkin, who first described what came to be known as Hodgkin lymphoma in 1832. Hodgkin lymphoma can be caused by DNA damage to a lymphocyte, which proceeds to grow into a mass that is typically concentrated in the lymph nodes. It’s characterized by large cancerous cells called Reed-Sternberg cells.
Non-Hodgkin lymphoma (NHL) refers to a group of more than 40 different subtypes of disease, each distinguished by specific types of cancer cells. As with Hodgkin lymphoma, non-Hodgkin lymphoma begins with changes within a white blood cell. Most cases involve B cells, which typically churn out antibodies to fight infection. But the disease can also start with T cells and NK cells, which are programmed to wage war against viruses or tumor cells.
When Allen first was treated for cancer in 1982, the protocol often called for more extensive radiation exposure and the use of chemotherapy that had a greater risk of the development of secondary cancers than current approaches. That could be why Allen developed non-Hodgkin lymphoma in 2009, says Dr. Ajay Gopal, clinical research director and medical director for hematologic malignancies/hematology at Seattle Cancer Care Alliance (SCCA). “I don’t know the details of his clinical case, but he could have been treated with an approach that gave rise to his non-Hodgkin lymphoma. The standard of care then was very different from today.”
Dr. Gopal discussed the basics of the disease in a short video published by UW Medicine. He also noted that it’s important to determine which specific subtype of non-Hodgkin lymphoma is present to zero in on the best treatment. “Our best chance for curing aggressive non-Hodgkin lymphoma is the first chance,” he says. “Often the diagnosis is not what you think it is.”
Each year, about 75,000 people will be diagnosed with non-Hodgkin lymphoma, according to the American Cancer Society. The average age of diagnosis is 60 to 65. Lymphomas present a double whammy: Because they represent cancer of the immune cells, patients are dealing both with cancer and with an immune system that isn’t working properly.
Treatment can include chemotherapy, radiation and bone marrow transplants, as well as clinical trials and watchful waiting. Data from a recent study in the journal Cancer found that patients treated at a center with specific expertise in lymphoma and hematologic malignancy had improved survival rates.
That expertise can extend to cutting-edge treatments that didn’t exist when Allen first learned he had non-Hodgkin lymphoma in 2009. In the past year and a half, CAR T-cell therapies have made headlines with their ability to take T cells from a patient’s blood, reprogram them to attack cancer cells and multiply them to vast quantities that are then reintroduced to the patient. The approach, which is offered at Seattle Cancer Care Alliance, has been lauded as a breakthrough in treatment. SCCA is one of the first cancer centers in the U.S. to offer both FDA-approved CAR T-cell therapies for non-Hodgkin lymphoma, Kymriah and Yescarta.
CAR T-cell therapies are available only for patients with specific types of B-cell lymphoma whose treatment has failed at least twice. It's not clear if Allen would have been eligible. Clinical trials are exploring expanded applications for CAR T-cells.
“It’s very exciting that we have these new treatment options that work where nothing else appears to work, but they can have life-threatening toxicity associated with their use and they require patients to be in good enough shape to get that treatment,” says Dr. David Maloney, medical director of the Bezos Family Immunotherapy Clinic at SCCA.
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