Bone Marrow Failure and Cytopenias Program

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals, exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma Programs. Today, I'm happy to be joined by Dr. Jarek Maciejewski, chair of the Department of Translational Hematology and Oncology Research. He's also the co-director of the bone marrow failure and cytopenia program and he is here today to talk to us about that program. Welcome, Jarek.

Jaroslaw Maciejewski, MD, PhD: Thank you for the invitation.

Dale Shepard, MD, PhD: Absolutely. Maybe to start off, we can tell our listeners a little bit about your role here at Cleveland Clinic.

Jaroslaw Maciejewski, MD, PhD: Well, I joined Cleveland Clinic some 20 years ago and I came from National Institutes of Health where I received the training in hematology. I have to say is that aplastic anemia and other bone marrow failure syndromes have been very instrumental to progress in hematology and therefore they have been a tool to investigate other diseases that affect bone marrow as well. The concept of stem cells or the concept of a procedure called bone marrow transplantation, is derived and based really on study of aplastic anemia. This contribution made these diseases a workhorse of hematology research. Now, when I came here, I wanted to build a program that takes advantage of the big volume of patients that Cleveland Clinic sees. Why is that? Because aplastic anemia and the individual bone marrow failure syndromes by themselves are relatively rare conditions so that in order to see enough patients, to have experience to be able to advise them based on large experience at the institution in dealing with patients, you have to have a total volume of patients that is big enough. And for that purpose, Cleveland Clinic is a perfect place.

Dale Shepard, MD, PhD: Excellent. Maybe as we start, we have a lot of people with differing backgrounds, can you define what is bone marrow failure? How do we define bone marrow failure?

Jaroslaw Maciejewski, MD, PhD: Bone marrow failure disorders can be either acquired or inherited. And it is not a surprise that the proportion of hereditary forms of bone marrow failure will be bigger in children and kids, in pediatric patients or young adults. The older we grow, the lesser is the impact of inherited genetics on the diseases and more the environmental factors play a role. But in general, bone marrow failure disorders are diseases in which the hemopoietic stem cells in the bone marrow is impaired in their function. And as a consequence, patients develop cytopenias or have a propensity to develop malignancies of hemopoietic systems later on.

Dale Shepard, MD, PhD: I'm guessing in children, it's easier to identify that the bone marrow isn't working properly, but how often are these misdiagnosed in older patients?

Jaroslaw Maciejewski, MD, PhD: Well, with the advent of genetics, we realize the role of hereditary factors has been always underestimated, but in general, we believe that it is more likely to encounter acquired syndrome or acquired disease in adult patients rather than in children, whereas the suspicion for hereditary factors is much greater.

Dale Shepard, MD, PhD: Tell me a little bit about the program that you have in place for bone marrow failure and cytopenias.

Jaroslaw Maciejewski, MD, PhD: Well, as mentioned, the bone marrow failure has been the topic of my interest since my fellowship, at the National Institute of Health. And this was inspired by the factors that my mentor's in, was a world expert in these diseases. And when I came here, I strived to establish a program that would provide as professional and intricate and high quality, top advice and care to patients with bone marrow failure at the Cleveland Clinic. And it is of course, a little bit serendipity that I came from this program and of course historically how it evolve was also the fact that based on my prior contacts and publications and stature on the field, I was able to attract a lot of patient from outside of the Cleveland Clinic regular reach, in other words, outside of Cuyahoga County and Ohio itself, essentially seeing patients from all over United States.

Dale Shepard, MD, PhD: Certainly a big component is patients from outside this area. How did COVID impact your ability to see these patients and treat them and manage them?

Jaroslaw Maciejewski, MD, PhD: This is a very interesting question. COVID has changed us in the ways that will be impactful beyond the COVID epidemics. We already at the Cleveland Clinic work on telemedicine, but I saying the COVID epidemics made the telemedicine absolutely necessary. And out of this necessity grew ways to see that future medicine, particularly for rare diseases or for patient affected by diseases who are geographically separated by long distances, telemedicine is really the way to go. On the one hand, we have the necessity to avoid contact and to advise patients what to do next and to others a treatment, adjust their medication without being able to see them in person.

But in addition to it, we realized that we picked up by this way, a lot of patients who otherwise would think that the only way to take advantage of our expertise is to travel to Cleveland and to visit Cleveland Clinic, whereby now it is possible to arrange a consult and thus we see patients from all over United States and of course, one fallout of this situation is that providing good care gives you good recommendations of other patients so this is a self-perpetuating process.

Dale Shepard, MD, PhD: How about the research side? I know a lot of the research you've done has been sequencing and has there've been a negative impact on your ability to get samples and move forward with research?

Jaroslaw Maciejewski, MD, PhD: Well, the laboratory was closed for a while and our ability to collect samples for research at the same pace as it was before epidemics was clearly impaired. However, I have to say that research component of the program in rare diseases like bone marrow failure syndromes, including aplastic anemia, paroxysmal nocturnal hemoglobinuria and other diseases, it's intricately connected with the success of this program. In other words, clinical disease program and rare diseases are always intricately linked to laboratory research. This way, it is possible to provide patients with rare condition with the most up to date treatment modalities and ways to manage their disease. I have to say that whereas certain areas of medicine can be perfectly done without backup or be without background of the laboratory research, one cannot run a successful program in many areas of oncology or hematology without having a first class academic program and track record of publications and research in this area.

Dale Shepard, MD, PhD: These tend to be rare diseases you're dealing with, what's the ability to provide clinical trials?

Jaroslaw Maciejewski, MD, PhD: Well the problem with rare diseases is of course that in order to be able to organize trial, one has to rely on geographically large drawing areas, catchment areas for patients. For instance, you can calculate that if a disease's frequency is 16 million and in a given urban area, three million people reside, you can already epidemiologically expected only a limited number of cases. And of course not all patients will want to participate in clinical trials or will be candidate for the particular treatment modality. The mantra is of course, a part of having as large as possible draw area, catchment area, also to collaborate with other institutions and do multi-institutional protocols that give access to this limited number of patients at your institution, but the combined experiences of several institutions so that a systematic experience can be collected and publish to allow decisions in terms of the FDA approval of particular drug or it just gives the guidelines how to use particular new treatment modality for a subgroup of patients.

Dale Shepard, MD, PhD: How do most patients find you? Is it by doing their own sort of research? Is it interest sort of the support groups? By their physicians? How do most people participate in your program?

Jaroslaw Maciejewski, MD, PhD: This is a very good question. Obviously we rely a lot on the fact that large clinical volume in all areas of medicine in all diseases will create also a certain enhanced access to the rare diseases. You have to see this many frequent diseases in order to see one case of rare disease. But the most important is really to provide care that patients talk about it. And again, this changed in the last two decades tremendously because patients with rare diseases tend to organize online clubs or interest groups. They self-organize, they talk about it. And this is one of a major sources of referrals. Whereas patient feels that either they could be treated better or they want reassurance that they receive the best treatment or they are not responding to particular treatment and they would obtain a different view, they look of course and ask from other patients where you would go and how was your experience? And if this experience is positive, they will come to us.

The other aspect of care of rare diseases is to collaborate with physicians who sees a patient outside. And this is very important because for many of the doctors seeing a very complicated or intricate case, might constitute a burden, but many doctors don't like to give up their patients. We try, strive in our program to be as helpful as possible to referring physicians and to try to help them to manage as much of the disease as they wish. And in that realm some doctors, when they realize that they deal with a very complicated, rare conditions that they are not feeling comfortable with, they would give us the driver position, if you wish, in the care of this patient. But those other doctors might feel comfortable just to be reassured that they are on the right track and only at certain junction of the treatment of a particular patient, they will inquire, "Hey, what would you do? Would you continue? Do you think that we should exchange the treatment for another treatment?"

Now, this is very important, particularly if it saves a patient travel and aggravation of frequent visits somewhere far away and many of the patients also feel very comfortable with their doctor and they don't want to give it up. And my task is not to make it either or issue, but to draw the doctors from outside to become a part of this of the treatment team.

Dale Shepard, MD, PhD: Speaking of the team, what other members of the team do you have involved? Do you have a social work for instance, to provide social support? Patients with rare diseases oftentimes feel a bit lost.

Jaroslaw Maciejewski, MD, PhD: Well, this is excellent question. We are slightly different than many of the oncologic disciplines because we don't rely as heavily on imaging and on a collaboration of surgeons, like for example, sarcoma oncologist or breast cancer oncologist. Whereas of course the radiation oncology and surgical subspecialties play a major role. In bone marrow failure syndromes, in hematology in general, our team consists of us, the primary hematologists, the pathology and molecular pathology. Whereas increasingly sequencing and very intricate genetic studies are essentially very important to establish the diagnosis and to guide the patient through the treatment. Our team consists of us, the primary care hematologist, in collaboration with a group of pathologists who specialize in this type of conditions. Many of our patients eventually might be candidates for bone marrow transplantation so we are of course, very close related to the bone marrow transplant program.

If we deal with hereditary diseases, our team will involve at certain point genetic counseling or a clinical geneticist. And we have in our team doctors and advanced practitioners who specialize in genetic counseling. Social work is ubiquitous. We see patients with insurance issues. We see patients who are far away. We see patients who have to, in order to receive better care, like for example, in the case of bone marrow transplantation, have to relocate closer to the clinic in order to receive successful treatment. The social worker is very, very important.

And finally, I want to mention that the price of current medicine is steadily increasing, which produces a lot of pressure on prescribers and on the patient and from the respective insurance and programs that provide these drugs. And what is unique about our program and very important in general is to have a very good collaboration between pharmacy and authorization team for the drugs, that we are successful to obtain the best medicine for the patient, irrespective of patient's financial resources. And that we doctors don't have to worry as to problems with insurance because we have a support team which gives us a lot of cover, if you wish, in obtaining the best medicine for a given patient, irrespective of the insurance.

Dale Shepard, MD, PhD: What do you think are the biggest gaps in making forward progress? And what do you see as the most promising new therapies?

Jaroslaw Maciejewski, MD, PhD: Well, as mentioned, there are the peculiarities of dealing with a rare condition. One is of course, that it's difficult to gain experience unless you see a large volume of patients, which of course is difficult when the disease is rare. And this way, of course the progress is much slower. The clinical trials require more coordination between centers, but also commercially the interest of companies to develop drugs for rare diseases has been limited.

However, this is changing as well because more and more many of the pharmaceutical companies realize that there can be a substantial financial success to them by developing very effective, very modern drugs even for our conditions. And we have couple of example historically where record pricing for drugs for rare disease have been logged in. And I would never previously imagine that this would be possible and supported by that this type of pricing would be ever successful to implement. Yet through innovation, many of the major pharmaceutical companies realize that rare diseases might eventuality constitute a major portion of their portfolio and are developing the drugs irrespective of the cost and the difficulty in conducting clinical trials with few patients.

Dale Shepard, MD, PhD: Well, thank you very much for your insight. Do you have any additional comments?

Jaroslaw Maciejewski, MD, PhD: Well, I would like to send the patients who trust, and trust us with their care and their problems. We love to see more of you. We would like to be helpful to the hematologists outside of our centers to manage these patients. And this is a two way highway from every case through the research program and academic programs that accompanied our clinical program, we try to learn more. We try to write it down. We try to publish it so that if I am able to talk to you about or to a patient about his or her disease for 20 minutes explaining what we know about it, this is thank to other patients who previously donated blood sample, bone marrow samples or agreed to participate in clinical trials so that next generation of patients can benefit from us being able to provide more skilled and more professional advice.

Dale Shepard, MD, PhD: Well, thank you very much.

Jaroslaw Maciejewski, MD, PhD: Thank you very much as well.

Dale Shepard, MD, PhD: This concludes this episode of Cancer Advances. You will find additional podcast episodes on our website, clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google Play, Spotify, SoundCloud or wherever you listen to podcasts. And don't forget you can access real time updates from Cleveland Clinic's Cancer Center experts on our Consult QD website at consultqd.clevelandclinic.org/cancer. Thank you for listening, please join us again soon.