What Ryan O'Neal's Story Can Help Us Understand About Chronic Myeloid Leukemia

Twenty-two years, and a cause of death that was not cancer

Ryan O'Neal starred in Love Story, Paper Moon and Barry Lyndon. He died on 8 December 2023 at the age of 82, his son Patrick announced.

NBC News reported that he was diagnosed with chronic myelogenous leukemia in 2001 and with prostate cancer in 2012. Deadline reported later that month that his death certificate gave congestive heart failure as the cause, with cardiomyopathy, a disease of the heart muscle, as the underlying cause. No other cause was listed.

So this is a story about living with a blood cancer for more than two decades, not about dying from one. That is now an ordinary outcome in this disease, and it was not always.

One swap between two chromosomes

Chronic myeloid leukemia, also written chronic myelogenous leukemia, is a slow blood and bone marrow disease in which the marrow makes too many white blood cells. NCI notes it usually appears during or after middle age and is rare in children.

Almost everyone with CML has the same underlying change. Pieces of chromosome 9 and chromosome 22 break off and trade places. The ABL1 gene from chromosome 9 lands next to the BCR gene on chromosome 22, forming a fused gene called BCR::ABL1. The altered chromosome 22 is known as the Philadelphia chromosome.

That fusion gene builds a protein called a tyrosine kinase, which is stuck permanently switched on. It drives stem cells to become white blood cells without stopping. Marrow that should make a balanced mix of cells makes one kind, endlessly.

NCI adds a point that matters to families: the Philadelphia chromosome is not passed from parent to child. It happens in a single cell during a person's life.

Our page on leukemia covers how the different types are told apart.

Three phases, defined by one number

CML is not staged like a solid tumor. It is classified by phase, and the phase is set by the share of blast cells, which are immature blood cells, in the blood or marrow.

• Chronic phase: fewer than 10% blasts. Most people are diagnosed here.
• Accelerated phase: 10% to 19% blasts.
• Blastic phase: 20% or more blasts. When tiredness, fever and an enlarged spleen occur together in this phase, it is called blast crisis.

As blasts fill the marrow there is less room for healthy red cells, white cells and platelets. That produces anemia, infections, easy bleeding, bone pain, and pain or fullness under the ribs on the left, where the spleen sits.

Diagnosis uses a complete blood count with differential, blood chemistry, and examination of blood and marrow for the Philadelphia chromosome and the BCR::ABL1 gene.

The drug that arrived the same year

The treatment NCI lists first for chronic-phase CML is targeted therapy: asciminib, imatinib mesylate, nilotinib, dasatinib or bosutinib. Allogeneic bone marrow or stem cell transplant, using donor cells, is the other listed option.

These drugs are tyrosine kinase inhibitors. They block the very protein the Philadelphia chromosome produces. Because the target exists only in the leukemia cells, the treatment is far more selective than conventional chemotherapy. Our page on targeted therapy explains that principle.

The timing here is striking. FDA records show imatinib, sold as Gleevec, received its original approval on 10 May 2001, under priority review. That is the year O'Neal was diagnosed. He was among the first cohort of patients for whom CML started to become something people manage for decades.

Treatment differs by phase. In accelerated phase NCI lists bosutinib, or imatinib followed by an allogeneic transplant. In blastic phase it lists imatinib, dasatinib, nilotinib or bosutinib, transplant, and chemotherapy given to relieve symptoms and improve quality of life.

Two cancers in one person

O'Neal's prostate cancer diagnosis in 2012 came eleven years after his leukemia. Having one cancer does not protect against another, and it complicates decisions: drugs interact, organs already under strain tolerate less, and two teams have to agree on sequencing.

This is increasingly common precisely because people now survive a first cancer for many years. Our page on survivorship covers the long follow-up that comes with it.

When to get checked

There is no screening test for CML, and it is often found by chance on a routine blood count. NCI lists these as reasons to see a doctor, while noting that other conditions cause them far more often:

• Feeling very tired, without an explanation.
• Weight loss for no known reason.
• Drenching night sweats.
• Fever with no obvious infection.
• Pain or a feeling of fullness below the ribs on the left side.

NCI also states plainly that CML sometimes causes no symptoms at all. A persistently high white cell count on a blood test taken for another reason is a common way it surfaces, and it deserves an explanation rather than a repeat test alone.

The numbers

About 9,650 new cases of chronic myeloid leukemia in the United States, and about 1,170 deaths, are projected for 2026 by the American Cancer Society. SEER lists them but does not calculate them. Five-year relative survival, which SEER does calculate, was 71.1% for people diagnosed between 2016 and 2022. The median age at diagnosis is 67, and around 76,692 people in the country were living with CML in 2023.

Those figures average across all phases and all ages, and they lag behind current treatment. They describe a population, not a person.

What this does not mean

Living well with CML for twenty-two years is not a promise to anyone else. Phase at diagnosis, response to the first drug, other illnesses and access to treatment all vary.

Nor was his death a cancer outcome. The certificate named heart disease, and reporting a death accurately matters more than making it fit the story people expect.

And a targeted drug only works where its target exists. The reason CML responds so well is that one identifiable protein drives it. Most cancers are not built that simply.

Sources

• NBC News, Ryan O'Neal, 'Paper Moon' and 'Love Story' actor, dies at 82 — https://www.nbcnews.com/pop-culture/pop-culture-news/ryan-oneal-paper-moon-love-story-actor-dies-82-rcna128827
• Deadline, Ryan O'Neal Cause Of Death Revealed — https://deadline.com/2023/12/ryan-oneal-cause-death-revealed-1235681370/
• NCI PDQ, Chronic Myeloid Leukemia Treatment (Patient Version) — https://www.cancer.gov/types/leukemia/patient/cml-treatment-pdq
• FDA, Drugs@FDA record for GLEEVEC (imatinib mesylate), NDA 021335 — https://api.fda.gov/drug/drugsfda.json?search=application_number:%22NDA021335%22&limit=1
• SEER Cancer Stat Facts, Chronic Myeloid Leukemia — https://seer.cancer.gov/statfacts/html/cmyl.html

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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