Jurassic Park actor Sam Neill was recently interviewed by The Guardianopens in advance of the release of his memoir, Did I Ever Tell You?
Originally planned as a glimpse into his career, his life as a celebrity, and his farm in New Zealand, the book takes a dark turn in chapter 1: “The thing is, I’m crook. Possibly dying … I may have to speed this up.” Neill revealed that he had been diagnosed with stage III angioimmunoblastic T-cell lymphoma (AITL).
Neill first noticed swollen glands during the publicity tour for “Jurassic World Dominion“ in March 2022. He was initially treated with standard chemotherapy, but when that began to fail, he started a second drug, which he will continue to receive monthly for the rest of his life. The medication seems to be working, despite Neill feeling poorly and having a loss of appetite after every treatment: “I’m not off the hook as such, but there’s no cancer in my body.”
Neill started writing the memoir to keep from getting bored during treatment. But it turned out to be much more — in fact, “a lifesaver.”
“I never had any intention to write a book,” he wrote. “But as I went on and kept writing, I realized it was actually sort of giving me a reason to live and I would go to bed thinking, ‘I’ll write about that tomorrow … that will entertain me.'”
Neill went on to say: “I can’t pretend that the last year hasn’t had its dark moments. But those dark moments throw the light into sharp relief, you know, and have made me grateful for every day and immensely grateful for all my friends. Just pleased to be alive.”
Angioimmunoblastic T-Cell Lymphoma
AITL is a rare form of non-Hodgkin lymphoma (NHL). It is classified as a peripheral T-cell lymphoma (PTCL), a heterogeneous group of generally aggressive neoplasms which accounts for about 15% of NHLs. AITL accounts for about 1-2% of all people with NHL. It occurs most commonly in people in their 60s and 70s.
In the U.S., the median overall survival following a diagnosis of AITL was 22 months, according to a 2004-2016 analysis of the National Cancer Databaseopens in a new tab or window, ranging from 17.2 months for patients with stage IV disease and 35.1 months with stage I disease.
The cause of AITL is unknown at the present time, but research has suggested it may be linked to infection with viruses such as Epstein-Barr virus, cytomegalovirus, or herpesvirus type 6.
It’s well known that genetic mutations can induce abnormal immune activity and inflammatory disorders. Genomic profiling has identified mutations in the Ras superfamily proteins, epigenetic regulator genes, and relevant signaling pathways in patients with AITL. Mutations in the Ras homolog family member A (RHOA) gene are present in 50-70% of patients. Other mutations are outlined in a paper by Yu and Zhangopens in a new tab or window.
Histologically, AITL is characterized by partial or total architectural effacement of lymph nodes by mature T-cell lymphoma derived from CD4+ T follicular helper cells, along with a polymorphous infiltrate of reactive cells. There is also prominent hyperplasia of high endothelial venules and follicular dendritic cells.
Signs and Symptoms
Patients with AITL typically present with acute, generalized symptoms although, less commonly, they may present with asymptomatic lymphadenopathy.
Symptoms frequently include:
- Systemic symptoms of high fever, night sweats, or weight loss
- Generalized lymphadenopathy is present in 76-95% — with neck, axilla, and groin nodes most often affected
- Hepatomegaly
- Splenomegaly
- Morbilliform, erythematous, or pruritic rash is found in 40-60% of patients; on biopsy, this is seen as lymphohistiocytic vasculitis
- Polyarteritis
- Ascites and effusions
- Anemia and symptoms associated with anemia (from an autoimmune hemolytic anemia)
Almost 90% of patients have advanced (stage III/IV) disease at the time of diagnosis. The bone marrow is involved in 30-60% of patients and there is extranodal involvement in about 25% of patients.
Treatment
Standard therapies used to treat individuals with AITLopens in a new tab or window include corticosteroids and single- or multi-agent chemotherapy, according to a guide from the National Organization for Rare Disorders (NORD). The most commonly used multiagent chemotherapy combination is CHOP (cyclophosphamide, doxorubicin hydrochloride [hydroxydaunorubicin], vincristine sulfate [Oncovin], and prednisone).
“The initial response to CHOP is often good, but the overall effectiveness of CHOP and other chemotherapy regimens has largely been inadequate. Although many individuals initially experience a remission, most will eventually experience a relapse,” according to the NORD report. “One promising therapy for the treatment of AITL is the use of high-dose chemotherapy followed by autologous stem cell transplantation.”
In 2011, romidepsin (Istodax) was approved by the FDA for the treatment of PTCL. However, in 2021 the drug was withdrawn from the U.S. marketopens in a new tab or window when a confirmatory trial failed to meet its primary endpoint.
A variety of drugs have been used or are being studied to treat individuals with AITL, and some have reportedly resulted in complete remissions for some patients. Some newer agents that have shown promiseopens in a new tab or window include brentuximab vedotin (Adcetris), lenalidomide (Revlimid), and panobinostat (Farydak). A list of clinical trials regarding AITL can be found at ClinicalTrials.govopens in a new tab or window.
Michele R. Berman, MD, is a pediatrician-turned-medical journalist. She trained at Johns Hopkins, Washington University in St. Louis, and St. Louis Children’s Hospital. Her mission is both journalistic and educational: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.