Medical report: Chuck Pagano and acute promyelocytic leukemia

The news that Indianapolis Colts head coach Chuck Pagano has started chemotherapy for a rare form of cancer known as acute promyelocytic leukemia (APL), while devastating to the team, city, and entire NFL community, comes with a silver lining: under the proper medical care and with a timely diagnosis, it is a treatable condition associated with a favorable prognosis.

News came yesterday regarding Pagano’s condition after he had reportedly complained of fatigue and bruising dating back to the preseason. Both of these symptoms are potential signs of leukemia, a type of cancer of the blood or bone marrow, and tests conducted last week, while the Colts were on a bye, confirmed the specific diagnosis of APL.

In a twist of good fortune, the fact that the team did not play last week may ultimately have saved Pagano's life. Because successful treatment depends to an extent upon early diagnosis, his ability to take time off from head coaching duties and seek medical care allowed Pagano to be tested and receive care before the condition progressed significantly.

Pagano, age 51, is expected to spend the next 6-8 weeks at the Indiana University Simon Cancer Center receiving and recovering from an initial round of chemotherapy, and then is likely to continue treatment for up to several years to hopefully achieve and maintain remission. Pagano falls within the typical age range of individuals who develop APL – it is most commonly diagnosed during middle age – although it can be diagnosed at any age. It is rare, occurring in approximately 1 in 250,000 people in the United States, and occurs due to a mutation of two genes whose genetic material are rearranged due to random happenstance. This type of genetic change, called a translocation, is not inherited from or passed along to family members.

APL is a form of acute myeloid leukemia, a cancer of the bone marrow. In normal bone marrow, stem cells produce red blood cells that carry oxygen, white blood cells that protect the body from infection, and platelets that are involved in blood clotting. In APL, immature white blood cells called promyelocytes increase in abnormal numbers and accumulate in the bone marrow. The overgrowth of promyelocytes leads to a shortage of normal white and red blood cells and platelets in the body, which causes many of the signs and symptoms of the condition.

Individuals with APL are especially susceptible to a number of abnormal clinical symptoms, including fatigue, bruises, nosebleeds, bleeding from the gums, or blood in the urine. The abnormal bleeding and bruising occur in part because of the decreased number of platelets in the blood and also because the cancerous cells release substances that cause excessive bleeding.

The low number of red blood cells (anemia) can cause individuals with APL to have pale skin or fatigue. In addition, affected individuals may heal slowly from injuries or have frequent infections due to the loss of normal white blood cells that fight infection. Furthermore, the leukemic cells can spread to the bones and joints, which may cause pain in those areas.

Other general signs and symptoms may occur as well, such as fever, loss of appetite, and weight loss. Treatment of APL requires cycles of multiple therapeutic agents, including chemotherapy, in three distinct phases: induction, consolidation, and maintenance. In the induction stage, patients typically receive a chemotherapeutic drug along with a medication called ATRA , in hopes of rapidly eradicating the promyelocytic white cells.

While the medications are only given over a few days in the induction phase, patients such as Pagano are advised to stay in the hospital for weeks thereafter due to the risk of life-threatening infections that can arise while the white blood cell counts slowly recover.

After the patient has returned home from the hospital, the next stage of treatment is consolidation, in which patients receive several additional rounds of chemotherapy to build upon the effects of induction. Finally, during the maintenance phase patients receive multiple medications – some daily, some for weeks at a time on an occasional basis – typically for 2-3 years after the end of the consolidation stage.

Overall, treatment is a lengthy process, and the medications themselves carry numerous side effects including nausea, headaches, significant drying of the skin, and the aforementioned lowering of blood counts, but with a remission rate around 90 percent it carries one of the most favorable prognoses among cancers.

To be sure, even despite the postitive prognostic outlook, Pagano’s road ahead will have its share of ups and downs. Colts owner Jim Irsay foreshadowed this point when he suggested it was "probably not in the cards that [Pagano] will be able to be all in this season," and based on the rigors involved with the intensive treatment regimen, it would stand to reason that Bruce Arians, who has taken over as interim coach, will most likely stay in that capacity throughout the season.

Nonetheless, given the therapies available to Pagano – and given his fighting spirit that has endeared him to his players and helped bring a new energy to the Colts in such a short period of time – there is great reason to believe he will beat APL and find himself back at the helm in Indianapolis one day.