Cancer is a scary word, and it once again entered the hockey world Monday when it was announced Brian Boyle has been diagnosed with chronic myelogenous leukemia.
The disease in the new center for the New Jersey Devils was reportedly found via his training camp physical, likely a routine blood test. His only noticeable symptom to this point had been a bit of fatigue.
It is the same diagnosis Jason Blake received almost a decade ago as a new member of the Toronto Maple Leafs. The winger, who at 34 was only a year off participation in the Olympic Games for the United States, was also reportedly diagnosed via a routine blood test at training camp.
Blake played 363 regular season games and six playoff games after his diagnosis, scoring 82 goals and 122 assists in the time. He stayed right on his career averages until age started to catch up with him until the last few years. So how can someone be diagnosed with a relatively aggressive cancer but continue to play and succeed in the NHL? That’s what we’re here to discuss.
First the typical disclaimer – I have only 10 weeks of formal medical training at this point and am nowhere near a true expert on even general medicine yet. Additionally, I have not treated and do not know the details specific to Boyle or Blake.
All cancer is driven by cells dividing furiously when they aren’t supposed to, and leukemia specifically comes in several flavors. The first division is between acute, which can be fatal within weeks or months if untreated, and chronic, which can progress to death in a matter of years. This is related to how much the cells mature before going crazy – acute leukemias are very immature cells while chronic leukemias come from slightly more mature ones.
In both types of leukemia, the two main issues are overcrowding and ineffective defenses. The immature white cells are dividing rapidly and push out other healthy cells that usually participate in clotting, oxygen transport and defense. The immune system takes a double whammy because the leukemic cells are also not able to do their job of patrolling for invaders, so people with leukemia are inherently more vulnerable to infections.
The other big categorizations in leukemia have to do with the type of cell that has gone crazy. There are two main lines with lots of smaller offshoots, and the middle word of the disease name (i.e., acute lymphoblastic leukemia) indicates the cell type.
In Boyle’s case, he has chronic myelogenous leukemia, and in a crazy way that’s actually a good thing, because CML is one of the great success stories of modern oncology.
All cancer is caused by mutations in the systems that control cell integrity and division. Most cancers have loads of mutations by the time they become clinically known, and this leads to treatment difficulties. The leukemias generally have fewer – as few as four in some types of childhood ALL – and CML in particular has a known, single driver mutation.
The vast majority of CML cases are caused by a flip of chromosomal material between the ends of chromosome 9 and 22. This translocation, called the Philadelphia chromosome, essentially takes two independent proteins and combines them into a single entity. This chimera (BCR-Abl for you biology nerds) takes a protein that is supposed to only be turned on at some points and makes constitutively active, on all the time. This drives cell division in the improper, immature stage and also inhibits DNA repair, making the cells prone to even more mutation.
The good news for patients is that this chimeric protein has a really distinct molecular shape with a big, deep pocket. In the 1990s, scientists working for Novartis designed a drug that fits into the cleft and turns off the “always on” activity, thus stopping cell division. This removes the danger of overcrowding and issues with DNA repair, and therefore stops the symptoms of the disease. Essentially, the patient is cured every way except genetically.
This drug, called imatinib (Gleevec), has turned CML from a deadly condition into a chronic, manageable one in the vast majority of cases. Clinical trials have shown if a patient responds to the drug, they remain at the typical “healthy person” risk of dying over at least the next eight years. Some of the original trial patients have been on Gleevec for more than two decades with no sign of progression or change in disease status.
Most people see this success and wonder why we can’t do it for every cancer. Why hasn’t this amazing approach been applied to things like cholangiocarcinoma (the disease Dave Strader has)? The answer is medicine tried but it hasn’t been successful. Targeted therapy, the category imatinib falls in, has some notable successes but is not nearly as useful in cancers with multiple driver mutations and that are genetically very heterogenous. Carcinomas, like Strader’s, can have hundreds of mutations and different pockets within the same disease that have different genetic profiles. Unfortunately, that means these TKIs just aren’t very effective outside of this narrow realm.
There are a small set of people with CML who don’t respond to imatinib and a few more who develop serious side effects. There are also some whose cancer changes just enough over time that the drug no longer fits in its pocket after a few years. In all those cases, there are second-line drugs with similar effects. For the very small percentage where none of these work, there is the potentially-curative bone-marrow transplant procedure. BMTs use high doses of nasty medicines to kill off all the immature blood cells – healthy and leukemic – then replace them with the immature blood cells of another person. While this theoretically eliminates the underlying problem, it also has huge risks of morbidity (side effects) and mortality (death) both in the immediate and long-term aftermaths.
But for someone like Boyle or Blake, that is years down the road if it’s necessary at all. For now, their disease can be managed almost analogous to asthma – medicine eliminates the dangerous symptoms even though the underlying condition is still there.
In all of medicine, particularly cancer medicine, there are no guarantees. Blake has responded beautifully to the treatment, a decade out from diagnosis at this point as far as we know. Boyle, thankfully, has every chance of following the same path.