This article is more than 5 years old. Information may no longer be current.
Invest in resources to help patients avoid dangers beyond disease
Click Here to Manage Email Alerts
William Wood
Ms. A, a charismatic and vivacious 22-year-old woman, was frightened and unwell when she first presented to our hospital a few years ago.
At the time, she had reported abdominal fullness and pain, and by an outside laboratory had “25% blasts” on a peripheral blood smear. She was admitted and found to have a white blood count of more than 400,000 cells/mcL. A bone marrow biopsy and analysis of the peripheral blood did not show blasts but revealed a diagnosis of chronic phase chronic myeloid leukemia.
A singular triumph
As a disease, CML captures so many of the themes that characterize modern oncology, and it remains a singular triumph in our field. CML used to be an inevitably fatal diagnosis, with a prognosis measured in a few years. Treatment was largely palliative, although one intensive option held out a hope for cure for patients such as this 22-year-old, for whom living a few years would not be considered a successful outcome.
This field, bone marrow and stem cell transplantation, enjoyed some of its greatest successes in CML. The graft vs. leukemia effect was remarkably high, the transplantation itself was generally well tolerated in this patient population, and the overall success rates were among the highest for any of the transplantable diseases, with more than 70% of patients cured of their CML with successful long-term outcomes.
Despite this success, bone marrow transplantation has never been a light undertaking. The required investment of resources — from a financial, physical and emotional standpoint, and from the perspectives of the patient, her family and her treating health care team — are arguably the most substantial in all of modern medicine.
Complications can and do happen. Success is never a guarantee, but the commitment patients and families make to invest anything and everything possible to try to save just one life is inspirational, and it is a major reason why many, myself included, entered this field of medicine.
Of course, CML has become known for more than relative success in bone marrow transplantation; this disease is the most well-known example in modern oncology of successful targeted therapy. With the development of imatinib (Gleevec, Novartis), an oral pill became available to keep chronic phase CML at bay permanently, in many cases obviating the need for bone marrow transplantation.
Imatinib has proved to be well tolerated, with side effects that are generally very manageable. With this drug, CML became a chronic disease with even less risk of long-term or permanent sequelae than other more well-known chronic diseases such as diabetes. The tremendous success of imatinib spurred expansion of a multibillion-dollar industry in personalized anticancer therapeutics, and cousins of imatinib — dasatinib (Sprycel, Bristol-Myers Squibb), nilotinib (Tasigna, Novartis) and, more recently, bosutinib (Bosulif, Pfizer) and ponatinib (Iclusig, Ariad) — have been subsequently developed to either compete with imatinib for frontline therapy or to be available for patients whose CML becomes resistant to first-line treatment.
The roles of imatinib-like medications and stem cell transplantation are in evolution. A plethora of articles have been published during the past few years to provide guidelines for disease monitoring and to define “treatment failure,” helping patients and physicians to determine when second- and third-line therapy are recommended, and when a patient should be referred for transplantation.
A limited window
Despite the effectiveness of these drugs, some patients may have diseases that progress despite them, and that behave more like CML used to behave before the imatinib era. For these patients, the window for transplant — as it used to be — is limited.
These issues lead to extremely challenging treatment dilemmas in specific circumstances.
In Ms. A’s case, her disease appeared to experience an initially adequate response to imatinib. Although because of treatment effects and lingering disease activity, her imatinib was changed to nilotinib a year later. A year after starting treatment with nilotinib, she seemed to have ongoing disease activity suggesting a suboptimal response, and she was referred to me to consider stem cell transplantation.
None of us take the prospect of stem cell transplantation lightly when considering a 22-year-old patient for candidacy, especially when medications are available that might allow us to avoid this possibility. I was relieved when careful questioning revealed that Ms. A had inadvertently been taking half of her prescribed nilotinib dose. Her disease activity subsequently improved after she increased her dose to the intended level.
Several months later, though, we were in a familiar position. Ms. A was taking her nilotinib at the prescribed dose. Her BCR/ABL transcripts, the hallmark of her CML disease activity, were again increasing. She was switched to her third medication, dasatinib, and our transplant preparations began in earnest. In the meantime, a variety of social and financial barriers to transplantation had arisen that would need to be addressed quickly.
In thinking about Ms. A, I was struck by how much her fight against CML was representative of so many of the major movements in clinical oncology during the past 15 years. She had tried three of the best examples of molecularly targeted drugs, representing years of research, hundreds of researchers and millions of dollars of drug development. Now she was thinking about transplant, a procedure that is the product of some of the greatest resource investment, on a personal and societal level, in contemporary medicine.
In some ways, this scenario is a testament to the humanism that is embedded within the modern anticancer crusade. We will — appropriately — stop at nothing for the chance to save one life.
Physicians’ responsibilities
One day last fall, before Ms. A could make it to transplant, she apparently became involved in an argument with a young man whom she knew. The argument escalated, and she was shot and killed. The young man apparently did not have a prior criminal record, and acquaintances later commented that they were shocked, based on what they thought they had known about the young man’s character. As far as we know, this tragic outcome was the product of emotional escalation and a deadly weapon, with an efficient and irreversible consequence.
In thinking about this in the weeks that followed the tragedy in Newtown, Conn., I couldn’t escape the irony of the circumstances surrounding Ms. A’s life. I began to wonder about our responsibilities, as physicians, for the health and welfare of our patients. As a subspecialist and medical oncologist, are my concerns confined to my patients’ cancers? Or given the profound ways that I become involved in the fabric of my patients lives, helping them in decisions that have extreme risks and life-changing consequences, should I also invest myself in concerns about other threats to their health and safety?
More generally, as a community of health care providers, medical scientists and society at large, if we are willing to invest everything we have in this war on cancer — research, drug development and the pinnacle of per-patient resource investment, stem cell transplantation — then shouldn’t we also care about other, equally life-threatening health challenges that our patients might face?
Dangers beyond cancer
Data from the CDC show that, in 2010, there were more than 31,000 firearm-related deaths in the United States. SEER data estimated that 610 patients died of CML in 2012. The firearm homicide rate in the United States is 43 times higher for 15- to 24-year-olds, Ms. A’s age category, than it is in other industrialized countries.
I am not suggesting that resources have been inappropriately invested in the war on cancer. I am proud of my involvement in a profession that values human life so greatly that our aspirations are enormous and our commitment is complete. We are finally beginning to see some of the large-scale successes that are emerging from this effort, even if some of our other “targeted” approaches are not nearly as efficacious.
On the other hand, the successes that we have experienced in oncology and stem cell transplantation are owed entirely to coordinated and dedicated research efforts over many years. If we are serious as a medical profession about addressing all of our patients’ threats to life and health, then we should start by encouraging —or at least allowing — research in other vitally important areas.
I was dismayed to read a recent piece in the Journal of the American Medical Association that described campaigns that have chilled CDC research into injury prevention and control related to gun violence. Recent efforts from the current administration to overturn these kinds of restrictions have been encouraging, and I hope that as a medical community we can support efforts to encourage additional research in this area.
I believe that, as physicians, we need to find ways to protect our patients by reducing the daily morbidity and mortality that comes from firearm violence in this country.
Ms. A’s life was precious, and in CML she faced a serious adversary. As an oncologist, I’m proud that my subspecialty was able to offer her modern oral molecular therapeutics, and ultimately a stem cell transplant that she never received, to address this threat. As a physician, I hope that my profession and colleagues at large can invest similar resources to help others like Ms. A avoid other dangers that are just as great.
References:
Center for Disease Control National Vital Statistics Report, Vol. 60, No. 3, Dec. 29, 2011. Available at: www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_03_tables.pdf. Accessed Jan. 28, 2013.
Center for Disease Control National Vital Statistics Report, Vol. 61, No. 6, Oct. 10, 2012. Available at: www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_06.pdf. Accessed Jan. 28, 2013.
Kellerman AL. JAMA. 2012;doi:10.1001/jama.2012.208207.
Richardson EG. J Trauma. 2011;70:238-243.
For more information:
William Wood, MD, is an assistant professor of medicine in the division of hematology/oncology at the University of North Carolina in Chapel Hill. He also is a HemOnc Today Editorial Board member. He may be reached at UNC Health Care System, Division of Hematology and Oncology, 101 Manning Drive, Chapel Hill, NC 27514; email: william_wood@med.unc.edu. You also may follow him on Twitter (@WoodBD).
Disclosure: Wood reports no relevant financial disclosures.