The Eye of a Survivor

While cure remains a goal, unique issues arise when treating professional and amateur athletes for hematologic conditions.

Athletic competition on an elite level depends on substantial training to optimize performance, and while many may not think of it, blood’s role is front and center.

“Having an adequate oxygen-carrying capability is critical for endurance and strength training, as well as cognitive ability such as complex decision-making,” said Alexandra M. Stevens, MD, PhD, assistant professor in the Department of Pediatrics at Baylor College of Medicine, and member of the leukemia program at Texas Children’s Hospital.

Other blood functions are crucially important, such as adequate white blood cell count to prevent infection in team environments and normal platelet counts to ensure clotting if injury occurs.

“Athletes need to have almost no limitations, in terms of fatigue and pain, when training and competing. They need to be able to perform at their best,” said Lewis Hsu, MD, PhD, professor of pediatric hematology-oncology and director of pediatric sickle cell at University of Illinois at Chicago. “Having a chronic disease basically has the potential to put the brakes on you when you want to go full throttle.”

Unfortunately, athletes – elite or otherwise – are not immune to the development of disease. The most famous athlete diagnosed with a life-altering disease is likely baseball player Lou Gehrig, whose disease amyotrophic lateral sclerosis, or ALS, is still referred to as “Lou Gehrig’s disease.”

Gehrig retired at the tail end of a Hall-of-Fame career. But, much more often, athletes are diagnosed with a life-changing disease in the middle of their professional careers, or even before they’ve begun. Thanks to advances in diagnosis and treatment, though, athletes with hematologic malignancies can expect to continue in their careers. ASH Clinical News spoke with doctors who have treated professional athletes living with blood diseases about the special considerations for their treatment and advances in treatment that have allowed patients to continue playing at the highest levels.

A Comeback Story

On top of the damage caused by a hematologic disease itself, side effects of the treatments can also affect athletic performance, explained Izidore S. Lossos, MD, head of the hematological malignancies site disease group at the University of Miami Sylvester Comprehensive Cancer Center.

Therapies for blood cancers can cause decreased blood count, anemia, weakness and fatigue, and gastrointestinal effects; other medications can induce damage to vital organs like the lung, heart, or kidneys.

“The reality is that, even if someone recovers from the disease, a team will very carefully evaluate risk before signing a contract,” Dr. Lossos said.

Dr. Lossos witnessed this when he treated Anthony Rizzo, who presented to Sylvester Comprehensive Cancer Center in 2008 for treatment of Hodgkin lymphoma. (Editor’s note: ASH policy is to protect patients’ identities. The patients referenced in this article are public figures who have spoken publicly about their illnesses and are therefore identified by their full names.) One year earlier, at age 17, Rizzo had been drafted to the Boston Red Sox and was playing minor league baseball in South Carolina. He came to Dr. Lossos with fatigue and edema of the legs and was diagnosed with stage III Hodgkin lymphoma and nephrotic syndrome.

“He was losing albumin in the urine, accumulating fluids, and gaining weight,” Dr. Lossos recalled. “His presentation was very complicated and, with nephrotic syndrome, renal failure was definitely a concern.”

Rizzo had an International Prognostic Score of 3, which is associated with a five-year overall survival rate of 78%.1 Dr. Lossos explained to Rizzo that there was a chance for cure, but that he had to stop playing baseball to receive treatment. Rizzo was started on standard of care ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine) therapy.

“In Anthony’s case – because we needed to think of his future – use of BEACOPP was not a consideration,” Dr. Lossos said. BEACOPP, more commonly used in Europe, has been shown to result in better initial tumor control for Hodgkin lymphoma, but ABVD is less toxic and has similar long-term outcomes.2

Bleomycin, which is used in both regimens, has the potential for interstitial pulmonary fibrosis, so Dr. Lossos and the care team closely monitored Rizzo with pulmonary function tests.

Rizzo started to show improvement after the first cycle of chemotherapy and was in complete remission after six cycles. His kidney function returned to normal. He was back to playing baseball by 2010.

Uncovering a Diagnosis

Running back James Conner was diagnosed with stage IIb Hodgkin lymphoma in 2015, while playing football for the University of Pittsburgh.

“James had been seeing a few different physicians for a host of symptoms that he thought were related to sinuses or allergies,” said Stanley Marks, MD, chair of UPMC Hillman Cancer Center in Pittsburgh, who treated Conner. Later, after receiving his cancer diagnosis, Conner also acknowledged that he had been experiencing night sweats but thought that this was a symptom of an infection.

According to Dr. Marks, Conner became concerned when he was lifting weights and looked in a mirror and saw that his face and chest were bright red.

“This time, his physicians discovered he had superior vena cava syndrome caused by a large mass in his chest that was pushing on the veins in the upper part of his body,” he explained. “He was referred to UPMC Hillman’s director, Robert Ferris, MD, PhD, a head and neck surgical oncologist, for a biopsy on the lymph nodes in his neck.”

Next, Conner was referred to Dr. Marks. The swollen lymph nodes in Conner’s neck were initially missed because his neck was so muscular, Dr. Marks noted, adding that the running back was fortunate that the blockage in his chest did not result in a catastrophic event before he received his cancer diagnosis.

Dr. Marks said that the optimal management of stage IIb Hodgkin lymphoma can be controversial. Standard of care is a six-month regimen of chemotherapy, but some physicians also recommend chest radiation, particularly in cases with masses as large as Conner’s.

“In his case, we decided against radiation because he had responded so well to the initial treatment. Adding radiation to his chest could be detrimental to his lungs or heart and his football career,” Dr. Marks said. “I talked this over with James and his mother, and I also ran the case by four other experts around the country and all agreed with that assessment.”

Conner was started on ABVD and, similarly to Rizzo, was monitored for lung injury because of bleomycin and heart injury because of doxorubicin.

Not long before Dr. Marks began treating Conner, research had demonstrated that an interim PET scan after two cycles of ABVD predicted outcome for Hodgkin lymphoma, and could indicate whether a patient would benefit from escalated therapy.3

“Fortunately, his scan was negative after two months and I was assured that we made the right decision not to give him radiation treatments,” Dr. Marks said.

Another study published around the same time suggested that patients who have negative findings on an interim PET scan after two cycles of ABVD could safely drop bleomycin from the regimen.4 If Conner had been diagnosed just a few years later, Dr. Marks said, he would likely have substituted brentuximab vedotin for bleomycin, a combination that has shown better progression-free survival compared with ABVD, regardless of interim PET findings.5

During his cancer treatment, Conner continued to work out with the University of Pittsburgh football team. He then completed his college career, was drafted by the Pittsburgh Steelers, and will play this year for the Arizona Cardinals.

Playing With a Chronic Condition

Billy Garrett Jr., the first known NBA player with sickle cell disease (SCD) has shown that it is possible to maintain a career in professional sports while living with a chronic hematologic condition.

SCD is associated with anemia that limits oxygen delivery and can cause metabolic acidosis, explained pediatric hematologist Dr. Hsu. Dr. Hsu treated Garrett during his college basketball career at DePaul University, and is still involved with his care as Garrett transitions to an adult provider.

According to Dr. Hsu, three unique factors have allowed Garrett to become a successful athlete. First, Garrett has the sickle hemoglobin-C disease (SC) disease, a less severe form of SCD. Second, Garrett comes from a family of elite basketball players who have encouraged and motivated him to maintain great physical condition his whole life. Third, Garrett has practiced excellent self-care and taken medications that limited the effects of his disease.

Dr. Hsu and Garrett worked with his coaches at DePaul to set up guidelines for Garrett’s success.

“He has learned over the years to take frequent rest breaks, for example,” Dr. Hsu said. “We worked with coaches to build in the time off the court during scheduled timeouts when he can catch his breath and hydrate.”

Garrett also prioritizes good temperature control to avoid concerns about vasoconstriction due to cold or excessive dehydration. “He knows that he has to gradually adjust himself to new environments,” Dr. Hsu said. “He brings an oxygen concentrator on plane trips so that even the mild hypoxia that can occur on a commercial aircraft would not cause a problem for him later.”

Dr. Hsu said that Garrett was hesitant to take any medication that could be considered a performance-enhancing drug. For example, the SCD drug voxelotor modifies hemoglobin and increases the affinity between oxygen and hemoglobin. Increasing hemoglobin allows higher amounts of oxygen to reach the muscles, which, in athletes, could improve stamina and performance.

“Theoretically, voxelotor could increase a hemoglobin level by 1 g/dL but we didn’t want to do that – his hemoglobin is already high enough,” Dr. Hsu said.

Also, any treatment that required monthly infusions, such as crizanlizumab, was not a good option for Garrett’s schedule. Instead, Garrett was able to benefit from another fairly new drug, L-glutamine, which has been shown to reduce acute complications of SCD.6

“We settled on L-glutamine because it did not raise hemoglobin, but works on red cell metabolism,” Dr. Hsu explained.

These treatment advances, combined with Garrett’s dedication to self-care and disease management, have allowed him to play in the NBA’s minor league for several years, including signing a 10-day contract with the New York Knicks in 2019.

Amateur Athletes

Treatment advances are extending to younger athletes, like the amateur athletes who Dr. Stevens sees in her practice. Most commonly, she treats children or adolescents diagnosed with acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL).

“For AML, therapy is intensive, with kids in the hospital for up to a month at a time,” Dr. Stevens said. “This treatment can last about six months and kids are not involved in any school-based sports during that time.”

Children and adolescent athletes with AML can work to maintain their level of conditioning through physical therapy, she added. However, some kids with AML will require bone marrow transplantation, which makes for a longer road to recovery.

“One of my favorite success stories is a runner whose coach noticed a change in his performance – he was running at the back of the pack. That led to a trip to the physician and a diagnosis of AML,” Dr. Stevens said. “The patient did great, underwent transplant, and is now back playing varsity sports.”

With a diagnosis of ALL, treatment can last more than two years, and the first nine months entail intensive treatment. “We tend to keep the majority of these kids out of school and out of sports,” Dr. Stevens said. “We don’t want them to get any infections that could slow or delay their chemotherapy.”

Although the drugs typically used for ALL have less cardiotoxicity, treatment with the mainstay steroids can affect performance.

“There are a variety of things that could potentially decrease children’s ability to effectively participate in sports after they are done with the intensive phase of treatment,” she said. “Quite a few people may never return to participating at the same level as they had before because of the toxicity of treatment.”

The Athletic Advantage

The three examples of professional athletes with hematologic conditions are powerful, but athletes are just like any other patient, Dr. Lossos said. Not all will be cured of their disease and not all will be able to return to athletics. There is a whole spectrum.

“Leukemias, for example, can be very debilitating and patients will experience muscle waste and weight loss,” Dr. Lossos said. “This type of disease doesn’t spare totally healthy people. Healthy people can still die.”

However, athletes diagnosed with a hematologic disorder have some built-in advantages.

At the time of diagnosis, pediatric athletes are often better conditioned and at an appropriate weight, Dr. Stevens said, two factors that help minimize treatment-related toxicities.

The same is true in adults, said William G. Wierda, MD, PhD, professor of medicine in the department of leukemia at the University of Texas MD Anderson Cancer Center. Dr. Wierda was involved in the treatment of NFL player David Quessenberry who was diagnosed with non-Hodgkin T-cell lymphoma shortly after being drafted by the Houston Texans in 2014.7

“Athletes tend to be fit and healthy, and take better care of themselves than the average person does,” Dr. Wierda said.

Their advantage is not only physical, but mental. “Because of athletes’ innate competitive nature, they often also have a great deal of self-discipline and tend to be motivated and invested in getting the most out of their treatment to return to athletics.”

In addition, many athletes have built-in support systems, Dr. Stevens added.

“The loss of sport is profound, but I have found that with team sports, the kids and coaches tend to be very close,” Dr. Stevens said. “This can be incredibly beneficial because it provides another layer of support.”

Put Me in, Coach!

Whether the patient diagnosed with a hematologic disorder is an athlete or not, the goal is always curative treatment, Dr. Wierda said.

“We won’t usually abbreviate treatment without good cause if it would compromise our ability to cure their disease,” Dr. Wierda said. “That is always our primary objective.”

Still, he acknowledged that it is possible to avoid certain drugs that might cause long-term damage to the lungs and heart. That is because, for many athletes, the ultimate goal after undergoing treatment for a hematologic disorder is a return to the sport that they love. The ability to return is, of course, based on whether the patient’s disease has gone into and remains in remission.

Dr. Stevens said that, for children with leukemias who experience remission, she typically requires a one-month delay before returning to play, after significant immunosuppression has ended. “That recommendation is well received by the parents, if not by the patients,” she said. “For the rare patient who cannot or does not want to delay engagement, we will create a modifiable conditioning plan with a coach so that they can be prepared to start playing as soon as it is safe.”

One of Dr. Stevens’ patients was diagnosed with Philadelphia chromosome–positive ALL at 13. After his battle with ALL, he was focused on being able to play football in his freshman and sophomore years of high school.

“Coming back my freshman season was much easier because I knew I had time on my side and I only had to get to a freshman level of playing,” the patient told ASH Clinical News. A relapse at the end of his sophomore football season required a bone marrow transplant and radiation.

“I didn’t have much time to get to a senior level of strength and endurance, but I worked hard to be able to put back on the pads and get back on the field,” he said.

In adult athletes the wait time may be similar, Dr. Wierda added.

The Road to Recovery

“As patients transition from intensive treatment to maintenance, they can begin to increase their physical activity and exercise and get back to a more aggressive training schedule,” Dr. Wierda said, adding that he has had the rare patient who continues to do physical activity during the intensive treatment phase, albeit with extreme caution.

“Team physicians are also brought into the loop when I’m caring for a professional athlete,” Dr. Wierda said. “The team physicians will often do their own assessment to determine if an athlete is ready to return.”

During his treatment for Hodgkin lymphoma, Conner continued non-contact training with the University of Pittsburgh. Upon completing his treatment, he was able to get back to the field, Dr. Marks said.

“When the Steelers were thinking about drafting him, they reached out to me about any long-term side effects to be concerned about in terms of James’ endurance, performance, and likelihood of injury,” Dr. Marks said. “None of those things were a concern.”

For Rizzo, it was not possible to play during active treatment, Dr. Lossos said, but he began to train after therapy ended and he prepared himself to go back after one year.

“I assessed his health for ability to go back to play,” he said. “Once we reached the one-year mark, he was doing well and we encouraged him to start to train.”

Dr. Lossos emphasized that some people diagnosed with cancer see “victory” as eliminating the cancer. “In Rizzo’s case, though, it was clear from the first moment we met that the only victory for him would be playing baseball,” he said.

Rizzo was able to make his major league debut with the San Diego Padres in 2011, three years after his disease went into remission.

Patients Off the Field

Just like any other survivor, professional athletes undergo routine follow-up.

“I see Rizzo about once a year,” Dr. Lossos said. “We are looking for lymphoma recurrence, as well as checking for routine things that may happen secondary to therapy.”

Rizzo also stays active in the cancer community that he joined when he was diagnosed. “Anthony was really a model for other patients,” Dr. Lossos said. “It is important for patients to know that somebody like him has had this disease, gone through all of the same things they are experiencing, and survived.”

Similarly, Conner started supporting other patients even while he was still undergoing treatment, Dr. Marks said.

“James would walk around the treatment area and give patients encouragement,” Dr. Marks said.

Garrett helps to build awareness of SCD as well. He recently organized a sickle cell awareness basketball team – SCD Hoops – that is competing in The Basketball Tournament 2021 broadcast on ESPN.

A new direction in the career path of Dr. Steven’s patient was also realized after his diagnosis. Instead of continuing to pursue football after high school, he switched his focus to physical therapy. “My plan is to help others who want to get back to the sport they love and help build a connection with them so they know nothing is impossible,” he said. “Eventually, I would love to have my own sports medicine and rehabilitation facility so I can focus on helping people who were like me.” —By Leah Lawrence

References

  1. Merck Manuals. International Prognostic Score in Hodgkin Lymphoma. https://www.merckmanuals.com/medical-calculators/IPS.htm. Accessed July 1, 2021.
  2. Mondello P, Musolino C, Dogliotti I, et al. ABVD vs BEACOPP escalated in advanced-stage Hodgkin’s lymphoma: results from a multicenter European study. Am J Hematol. 2020;95:1030-1037.
  3. Seshachalam A, Karpurmath SV, Rathnam, et al. Does interim PET scan after 2 cycles of ABVD predict outcome in Hodgkin lymphoma? Real-world evidence. J Glob Oncol. 2019;5:1-13.
  4. Johnson P, Federico M, Kirkwood A, et al. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma. N Engl J Med. 2016;374:2419-2429.
  5. Straus DJ, Dlugosz-Danecka M, Connors JM, et al. Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Lancet Haematol. 2021;8:E410-E421.
  6. U.S. Food and Drug Administration. FDA approved L-glutamine powder for the treatment of sickle cell disease. Published August 8, 2017. Accessed July 6, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approved-l-glutamine-powder-treatment-sickle-cell-disease.
  7. Klemko R. David Quessenberry, Spreading Hope. Sports Illustrated. Published December 12, 2017. Accessed July 6, 2021. https://www.si.com/nfl/2017/12/12/david-quessenberry-houston-texans-cancer.

Blood clots may seem more “benign” than a diagnosis of a hematologic malignancy, but, as seen in the stories of professional athletes such as Chris Bosh and Serena Williams, these complications can threaten careers and – in rare instances – lives.

As Stephan Moll, MD, of the University of North Carolina, explained to UNC Health Talk, there are several factors that make venous thromboembolism (VTE) particularly risky in athletes. First, VTE is often overlooked in this population. The symptoms of blood clots (such as pain, swelling, skin discoloration, and shortness of breath and chest pain in the case of pulmonary embolism) can masquerade as acute conditions such as a muscle strain or shin splints.

Athletes are at risk for developing VTE for a variety of reasons, including prolonged travel time to games, compression of veins due to unusually large muscles or unusual anatomy, or an increased risk of injury or surgery with contact sports.

While typical treatment of VTE includes anticoagulation, or thrombolytics or thrombectomy for extensive clots, the treatment for athletes must be tailored to their unique circumstances and risk of injury. For example, anticoagulation can be scheduled to maximize therapeutic time before the day of play, then blood thinners are interrupted on the day of play and resumed after the game to limit the risk of excessive bleeding in the case of injury on the field.

After a clot, anticoagulation strategies should be adjusted to balance the risks of recurrent VTE and bleeding events when the athlete is deemed healthy enough to return to play. Professional athletes may also have the resources to undergo personalized pharmacokinetic and pharmacodynamic studies to guide anticoagulation in this population. However, few data exist to guide decisions about resuming anticoagulation or returning to play after VTE. Generally, Dr. Moll noted, delays in resumption of anticoagulation or use of prophylactic anticoagulant doses may be necessary, although these practices could increase the risk for recurrent VTE.

Athletes who experience VTE are not necessarily barred from play, given the availability of direct oral anticoagulants, and, in consultation with hematologists or team physicians, they can weigh the risks and benefits of play.

Sources

  1. UNC Health Talk. The Athlete-Blood Clot Connection. October 8, 2019. Accessed July 12, 2021. https://healthtalk.unchealthcare.org/the-athlete-blood-clot-connection/.
  2. American College of Cardiology. Athletes and Anticoagulation: Return to Play After DVT/PE. October 19, 2016. Accessed July 12, 2021. https://www.acc.org/latest-in-cardiology/articles/2016/10/19/15/13/athletes-and-anticoagulation.