Walking a Mile in Their Shoes: How Does It Feel to Be Both a Doctor and a Patient?

What happens when a physician becomes a patient – forced to view the health-care community through a different lens? Some physicians may have difficulty relinquishing control of their treatment to the hands of another, while others gain a new appreciation for the patient experience.

For some physicians, though, the experience of being a patient begins well before they have completed medical school, motivating them to study their particular disease. ASH Clinical News recently spoke with three hematologist/oncologists who have a unique perspective on practicing medicine and conducting research: Each is both a physician and a patient with a hematologic disorder.

Holbrook Kohrt, MD, PhD

At the time of going to press, we learned that Dr. Kohrt lost his battle with hemophilia on February 24, 2016. Our thoughts and prayers go out to his family, friends, and colleagues.

Holbrook Kohrt, MD, PhD, is an assistant professor of medicine at Stanford Cancer Institute. He was diagnosed with severe hemophilia as an infant and his condition has been a part of his day-to-day life for the last 38 years, influencing his decision to become a physician.

ASH Clinical News: You were diagnosed with hemophilia at a young age. When and how were you diagnosed?

Holbrook Kohrt, MD, PhD: For most hemophiliacs, the diagnosis occurs after having a bleeding episode as a very young child. For me, at about two months old, I was having multiple episodes of bruising and joint bleeding, and they actually thought that my mother was abusing me.

My hemophilia diagnosis was made when doctors discovered that I had the spontaneous mutation, an inversion in the Factor VIII gene. There were no risk factors and no reason to suspect that I had hemophilia – hence, the allegations of some type of physical abuse were not viewed as absolutely crazy. Unfortunately, that process took a toll on my mother.

How did your diagnosis affect your childhood and the rest of your family?

The diagnosis of any chronic medical condition, where there is need for additional attention and focus, creates a complex environment for both a child and his or her relationship with siblings and parents. My father, as a pediatrician, felt like he should have been able to make the diagnosis earlier. He was also out there trying to help heal kids while his own child was home with frequent joint bleeds; I think he wanted to be able to take away the pain of the joint bleeds and to be able to help me more, as a physician should.

My mother and I spent an incredible amount of time together. The hospital I went to was three hours away, so we would have six-hour day trips in the car to visit the hematologist. That was a lot of bonding time, and we have remained close ever since.

Growing up, my three siblings probably felt a little bit slighted because they weren’t getting as much attention – like when I was hospitalized with hepatitis C after a blood transfusion and the joint destruction caused by so many repeated joint bleeds.

Now, though, we are incredibly close. It is impossible to get a word in edgewise when we get together. In the end, it has been something that brought us together and strengthened our bonds.

What initially prompted you to become a doctor? What field did you envision going into?

Since my dad was a pediatrician, I spent time in his clinic on the weekends. I always thought I would end up in some form of medicine. It was my dream as a kid. I considered going into pediatrics because that’s what my dad did, and he made it seem like that was the only form of medicine. Unfortunately – or fortunately – he did not get his wish. When I was in medical school, I realized the path I wanted to go down was hematology/oncology.

Where does your health stand today? What is your current treatment regimen?

I have severe hemophilia and have received most standard therapies, but I recently developed an inhibitor to Factor VIII. I have multiple treatment options, but, unfortunately, none is working.

I am on an experimental therapy, ACE910, that is only available through a very specific law in Belgium. The “urgent case law” allows a physician there to write a prescription for an investigational drug still in development. That is how I get my care today, but it means I have to go to Belgium once a week to receive treatment. I have been living outside of the United States since May 2015 and dealing with my inhibitor since August 2014. It has been a year and a half, and it has been challenging.

How would you say your ongoing experience with hemophilia has shaped you as a physician?

As a physician and a patient, one always remembers the power and the capacity to be trusted. I think that patients come in the door and trust us immediately; I came into my own physician’s room and I trusted him immediately. We have to respect that because it is a type of trust that is given to us completely and blindly.

It helps me maintain perspective that what I do has great weight in patients’ lives. I need to put in 150 percent because what I do will have a clear impact.

It is amazing how children develop relationships with a specific person who personifies the role of “doctor.” That was true in my case. My first hematologist was African American, and my second was Caucasian. I told my second hematologist, who became chief of staff at the Children’s Hospital of Philadelphia, that he wasn’t allowed to be my hematologist because he wasn’t black. I think this is true for adults, too. We presume that those people are out there as our best advocates. Therefore, we, as doctors, should always treat our job with that much respect.

 

Lukas D. Wartman, MD

Lukas D. Wartman, MD, is an assistant professor in the Department of Medicine at Washington University School of Medicine in St. Louis, Missouri. In 2005, as a fourth-year medical student, Dr. Wartman was diagnosed with acute lymphocytic leukemia (ALL).

Since his diagnosis, Dr. Wartman has undergone several rounds of intensive chemotherapy, treatment with a targeted therapy, and two hematopoietic cell transplants. As head of the Genomics Tumor Board at Washington University in St. Louis, Dr. Wartman is able to offer patients the same type of genomic sequencing that helped his physicians find a targeted treatment for his leukemia. He believes his personal experience with a hematologic malignancy has made him more compassionate to the patient experience.

ASH Clinical News: What initially prompted you to want to become a doctor, and what field did you envision going into?

Lukas D. Wartman, MD: I wanted to be a doctor because I was interested in biology, but I wanted to devote myself to a career that was directly involved in helping people. Rather than becoming a basic researcher, the intersection between my love of biology and treating patients seemed to be a career as a physician, especially as a physician-scientist.

The weird thing about my story is that I would have been an oncologist even if I had not had this personal battle with leukemia. Starting in my undergraduate years, I was really fascinated by the molecular biology of cancer. At that time, oncology was one of the clearer examples of how specific alterations could drive a disease and how targeted therapies could try to eradicate that disease. I was drawn to that idea. During my second year of medical school, I took a hematology course with a great mentor, Scot Hickman, MD, and, during my fourth year, I worked with him at the oncology clinic at the veterans’ hospital here in St. Louis. Those experiences cemented my interest in going into oncology as a career.

A few months after that rotation, I was diagnosed with leukemia.

How were you diagnosed with leukemia?

At the end of my fourth year at Washington University, I felt fine and was looking at residency programs and interviewing for different residency spots all over the country. I started noticing, though, that I was feeling more fatigued than normal. I attributed it to having been very busy for the last few months and thought I had viral infection like mononucleosis. I rested, but instead of things getting better, things continued to progress. I started developing night sweats and was having bone pain and progressive fatigue. Up until this time I was perfectly healthy.

I had an opportunity to take a few weeks off and went back to stay with my parents outside of Chicago. I thought if I could just rest and recuperate I could get over whatever viral illness I had. I went home and things continued to get worse. My fevers started spiking one day so I went to an urgent care center and convinced them to draw bloodwork, which showed that I was pancytopenic and had some immature white blood cells circulating. They weren’t leukemic cells, but the abnormality was due to the disruption of my bone marrow. I immediately knew that this was bad news, and it meant that I likely had leukemia.

I came back down to St. Louis on a Sunday, had a bone barrow biopsy on Monday, and found out I had leukemia on Tuesday. It was later confirmed to be ALL. I dropped out of the residency match and instead was admitted to the hospital to start induction chemotherapy.

After being diagnosed with ALL did you question your decision to pursue a career in medicine?

Never. I think that many colleagues, including some of my professors in medical school, were concerned that maybe oncology wasn’t the best choice for me, given my own diagnosis. They thought I would be better served by going into a field with more distance between my own disease and my practice, but I never really questioned it or had any serious doubts about still pursuing medicine. More than anything, the diagnosis reinforced my commitment to studying leukemia and trying to come up with better therapies to treat the disease.

When did you return to medical school?

I was on a leave of absence from medical school while I was being treated – first with about nine months of intensive chemotherapy, then with maintenance therapy. When I started maintenance therapy, I joined a research lab and did a year of research while completing my chemotherapy. When that finished, I immediately finished my last month of medical school and enrolled into residency.

I completed two years of residency and my first year of clinical oncology fellowship at Washington University.

Where does your health stand today?

I was diagnosed in 2005, more than a decade ago, but have had two relapses since then.

Five years after I was initially diagnosed, I had my first relapse. I was treated again with aggressive chemotherapy and went on to have a bone marrow transplant, with my younger brother as the donor. Despite that aggressive treatment approach, I did extremely well and recovered uneventfully with no significant complications. I completed my clinical portion of my fellowship and joined the lab of Timothy J. Ley, MD, to start my post-doctoral research.

Three years after that, I relapsed again. I tried aggressive chemotherapy again, but it didn’t put me into remission. But, because I had the good fortune of being at Washington University and working on the genomics of leukemia, Dr. Ley and others decided to sequence my genome. Based on those sequencing results, they were able to identify a drug, sunitinib, which wouldn’t have ordinarily been used to treat my disease, but which put me into remission. I was able to get a second stem cell transplant from an unrelated donor in October 2011 and have remained in remission since.

I haven’t been able to continue to take sunitinib due to the side effects, and only took it for a very short time after the transplant. The biggest issue is that my transplant has been complicated by moderate to severe graft-versus-host disease.

What did sunitinib target?

When Dr. Ley and the genomic analysts looked at the whole-genome sequencing data, there were multiple alterations that were recognized as being relevant to leukemogenesis – none of which were targetable. Looking at the RNA sequencing results, they noticed that one gene, FLT3, was being overexpressed in my leukemia cells. FLT3 is one of the most frequently mutated genes in acute myeloid leukemia (AML), and there have been many, many trials with different FLT3 inhibitors in AML.

How would you say your ongoing experience with ALL has shaped you as a physician and physician-researcher?

It has granted me a unique perspective when it comes to interacting with patients with leukemia. We have many of the same shared experiences. Even with patients who are getting a transplant for something other than leukemia, I can relate to having gone through two transplants and having had a wide variety of complications related to the transplants. I hope that unique perspective helps me to be a better clinician.

While I am invested in the study of the genomics of cancer and leukemia, in particular, I have never fully focused on the genomics of my own disease. That was an intentional decision at the beginning to distance my research career from my diagnosis. I did not want to be studying my own genome or the genomics of ALL.

I have a strong commitment to continuing genomics research, which I think offers great potential for understanding the biology of leukemia. My goal isn’t to cure my own disease, but instead to find a niche within the research world where I can make a significant contribution. Hopefully that contribution, at some point, will improve patient outcomes.

David Fajgenbaum, MD, MBA, MSc

David Fajgenbaum, MD, MBA, MSc, is an assistant professor of medicine at the University of Pennsylvania; associate director, patient impact for the UPenn Orphan Disease Center; and co-founder/executive director of the Castleman Disease Collaborative Network (CDCN).

At age 25, during his third year of medical school, Dr. Fajgenbaum was diagnosed with idiopathic multicentric Castleman disease, a systemic form of Castleman disease that involves pro-inflammatory hypercytokinemia, reactive proliferation of lymphocytes, and life-threatening multiple organ system failure. His work researching the disease and connecting the global community of physicians, researchers, and patients has resulted in a major change in the way the disease is classified and has raised hopes that the disease’s etiology and pathogenesis will soon be elucidated.

ASH Clinical News: Did you always intend to go into medicine?

David Fajgenbaum, MD, MBA, MSc: I was always interested in health and medicine growing up. When I began college, I knew I wanted to become a physician, but that decision was strengthened further when my mom was diagnosed with glioblastoma about two weeks after I started my freshman year. The experience of having my mom diagnosed with this terminal brain tumor and watching her heroic battle gave me a laser focus on becoming a clinical oncologist to treat patients like my mom and, in parallel, wanting to drive forward cancer research. My mom passed away 15 months after her diagnosis, during my sophomore year of college. I channeled my sadness toward studying more and working harder so that I could train to become a doctor.

How and when were you diagnosed with Castleman disease?

After earning my undergraduate degree at Georgetown University, I had an opportunity to do a master’s program focused on cancer prevention at Oxford University. Then, I came back to the United States to the University of Pennsylvania for medical school. I was two years into my medical training, with a focus on becoming a hematologist/oncologist, when I went from being a healthy third-year medical student with no medical issues to being hospitalized in the intensive care unit at the University of Pennsylvania with an undiagnosed disease that was killing me.

I was first admitted to the hospital in August 2010 with flu-like symptoms, pancytopenia, kidney dysfunction, and anasarca. Over the next six months, I spent four-and-a-half months hospitalized, much of that time in the intensive care unit. I had a retinal hemorrhage and went blind in my left eye. I gained more than 50 pounds due to anasarca and needed dialysis and daily transfusions. I even had my last rites read to me in November 2010 when I was ill and not responding to chemotherapy.

About seven weeks into my disease course, I was diagnosed with HHV-8-negative, idiopathic multicentric Castleman disease – a subtype of Castleman disease that is very poorly understood.

Toward the end of that six-month period, I traveled to Little Rock, Arkansas, to the Myeloma Institute for Research and Therapy. Frits van Rhee, MD, PhD, gave me a combination of seven different chemotherapy agents – a multiple myeloma combination cocktail. I was so sick before the chemotherapy that I felt better with every dose of doxorubicin, cyclophosphamide, and etoposide, and my disease finally went into remission. Unfortunately, I have had two relapses since then.

How is living with the disease now?

Right now, I’m in complete remission with no sign of disease, researching and teaching at the University of Pennsylvania. However, this disease is incredibly episodic, and I know that I could be on my deathbed with complete multiple organ failure with incompatible-with-life lab values in just a few days from today.

Castleman disease is a complex disease. How do you explain it to someone who might not be familiar?

At its core, it involves activated immune cells releasing cytokines that can cause subsequent multiple organ dysfunction, but the etiology of HHV-8-negative multicentric Castleman disease is unknown.

It is heterogeneous: On one end of the spectrum, patients experience mild flu-like or mononucleosis-like symptoms; on the other end of the spectrum, patients experience sepsis-like multiple-organ system failure and die. Fluid accumulation or edema is common, as are multi-lineage cytopenias.

There are estimated to be about 5,000 new cases of Castleman disease a year, which makes it as common as Lou Gehrig’s disease. Castleman disease includes three subytpes: unicentric, HHV-8-associated multicentric, and HHV-8-negative or idiopathic multicentric. We know that the subtype that I have, idiopathic multicentric, brings with it a five-year survival rate of 65 percent, which is worse than the five-year survival for subtypes of non-Hodgkin lymphoma, Hodgkin lymphoma, and a number of hematologic malignancies that we have been able to make progress in.

There is, fortunately, one approved therapy, an anti-IL-6 therapy, siltuximab, but unfortunately, that drug does not work for all patients. Based on the only randomized controlled trial, one-third of patients had a response to therapy, and the other two-thirds were non-responders.

What led you to start the CDCN? What are the goals of this group?

After my first relapse, I started asking my doctor and other Castleman disease experts targeted questions about the disease such as, “What causes HHV-8-negative multicentric Castleman disease? What are the immune cell types that are driving this disorder? What are key cytokines other than IL-6 that may be driving the disease anti-IL-6 non-responders?”

I realized very quickly that no one had the answers, not even the world’s leading experts. I decided that I would dedicate the rest of my life to trying to solve the mystery of Castleman disease – to elucidate the etiology of my subtype, identify the pathologic immune cells and signaling pathways, uncover the cytokine cascade, and identify new treatments and even a cure. I dedicated my last year of medical school to conducting research into idiopathic multicentric Casteman disease under the mentorship of Arthur Rubenstein, MD. The result of that research was a review article published in Blood in May 2014 that outlined the current state of knowledge for the disease, presented a new classification system, and also proposed a new model of pathogenesis.1

That’s also when Dr. van Rhee and I co-founded the CDCN. We decided that we would take a global approach to taking on Castleman disease. Rather than raising funds and having people apply to use the money they saw fit, we would focus on global collaboration, identifying all of the physicians and researchers worldwide who are interested in Castleman disease. We would let them prioritize what research should be done and fund the right person to do each of the studies, while providing them with project management resources.

The goal of CDCN is to elucidate the underlying mechanisms behind Castleman disease and identify new treatments. The way we are going about doing that is building a network, prioritizing research, and driving forward a high-impact research agenda.

Our biggest milestone, thus far, has been constructing a new model for how we think the disease works, based on the collaboration and feedback from hundreds of physicians in the CDCN. The medical community used to consider the enlarged lymph nodes in multicentric Castleman disease to be “Castleman tumors”; these lymph nodes tumors were believed to secrete IL-6, and IL-6 caused organ dysfunction and all the downstream problems. What our new model proposes is that the enlarged lymph nodes are not the cause of cytokine release, but are a result or reactive process due to the cytokine release. Rather than thinking about it as a primary lymph node tumor, we need to think about it as a systemic inflammatory disorder. Now we have to find out why the cytokines are being released in the first place.

In the last year we launched four different research studies to try to understand the disease. This year we are preparing to fund another five to six studies. In aggregate, the 10 to 11 studies that we will be funding will further the research necessary to uncovering how this disease works.

Also, CDNC will be signing a collaborative partnership deal with a pharmaceutical company to establish a global patient registry and natural history study of Castleman disease, called ACCELERATE (www.CDCN.org/ACCELERATE). This is going to be a major step to help drive forward care for patients.

How has your experience with Castleman disease shaped you as a physician-researcher?

Being a patient has heightened my determination to ensure that my research and my colleagues’ research has the greatest potential to have an impact for patients. Researchers often can become focused on publishing papers and receiving grants, since that is how many of us are judged or evaluated for our careers. But that incentive structure will encourage researchers to do lower-risk studies that will certainly result in a paper, but maybe won’t answer the key question for a disease. Of course, that’s a broad generalization and certainly is not always the case.

However, being a patient with this disease means I couldn’t care less who publishes the paper from my research and whether or not I am an author. All I care about is figuring out this disease. I see what it has done in my life and what it does to thousands of other patients and their family members. I have friends who have lost their loved ones to this disease, and I know what it feels like to have the clock ticking for myself. I know that the clock is ticking for other patients with my disease.

I work with a sense of urgency that any moment wasted is a moment that could have saved someone’s life. When I’m looking at research, I am focused purely on its impact. How will this study contribute and how will this study potentially have an impact on a patient’s life? The last five years have included some of the most fun years of my life as I work with fellow clinicians, patients, and researchers – our Castleman warrior army – to take this disease down. I encourage anyone interested in joining the fight to visit www.CDCN.org or to email me at [email protected].


Reference

Fajgenbaum DC, van Rhee F, Nabel CS. HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy. Blood. 2014;123:-2924-2933.

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