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How I Practice Now: COVID-19 Effect on Transplants for Patients With Hematologic Malignancies

 

In this video, Mehdi Hamadani, MD, Professor of Medicine, Medical College of Wisconsin, Milwaukee, discusses the impact the global pandemic has had on bone marrow and stem cell transplantation for patients with blood cancers.

Transcript 

I'm Mehdi Hamadani. I'm a professor of medicine at Medical College of Wisconsin and lead the BMT and Cell Therapy Program. I'm also honored to be a speaker in the Great Debates and Updates in Hematological Malignancies.

COVID‑19 has a lot of ramifications for my practice. My practice mainly consists of patients who are undergoing a bone marrow or a stem cell transplant, cell therapies, or patients who are getting treatment for lymphomas.

COVID‑19, because of its global nature, is impacting every single aspect of a bone marrow transplant physician's practice.

Even before we started to see a lot of COVID‑19 patients within the US, a lot of stem cell transplant donors actually live in Europe. The activity of this virus and the associated travel disruptions in Europe were already impacting a transplant physician's practice in USA, way before we started seeing clinical patients with COVID in the US.

Around early March timeframe, both the American Society of Transplantation, as well as NMDP, which is the donor registry in US, put out a lot of very clinically relevant guidelines that impacted our practice.

A lot of people don't know, but when we do donor transplants on patients with blood cancers, the donor stem cells are typically collected, not in the transplant center, but in facilities elsewhere. A lot of those collections happen in Europe. Those stem cells are hand carried to our transplant facility, where those stem cells are infused fresh into a patient.

Imagine a global pandemic where travel is disrupted, the donor availability is impacted, because either the donor can't travel to a transplant center, or even if a donor can travel to a transplant center, you can't transport those stem cells back to the patient's transplant center in a different country.

In this epidemic, what we realized was that infusing fresh stem cells was no longer practical because we didn't want to be in a situation where we have already given patient a chemotherapy regimen that has destroyed their immune system and bone marrow but we can't get the stem cells there on time.

All the national registries in the US recommended procuring stem cells from the donors, transporting them to the transplant center and freezing the stem cells, and then starting the transplant procedure on the recipient. That was the biggest change in our practice immediately before we started seeing actual patients in US.

As the COVID rate started increasing in US, the next thing we realized was that COVID was taking a lot of hospital resources across the country. We were learning from what was happening in New York. I'm in Midwest, so we had time to prepare, learning from what was happening in the East Coast.

We very quickly realized that COVID patients' numbers were escalating very quickly. It was using a lot of emergency room resources, ICU resources, which immediately meant that we can't do transplant as a routine of care anymore. We had to make this very difficult decision of which patient needs transplant now and which patient's transplant can wait a little bit.

Right now, in my transplant center, and in many other transplant centers, what we are doing is there are patients with less aggressive cancers, at least in vast majority of them ‑‑ patients who have multiple myeloma, patient who have slow growing lymphomas who are undergoing an autologous transplant without a curative intent ‑‑ we are delaying those transplants until the COVID rates are going down.

Then there are patients who really need transplant as a curative procedure. Patients with diffuse large B‑cell lymphoma have very aggressive disease. If they are in remission, they need transplant quickly.

Same is true for patients with Hodgkin lymphoma. Their autologous transplants, we are trying our best to do them on time.

The donor transplant, we just talked about it. There is an aspect of getting the donor cells here logistically, which we are trying to figure out. In that respect, American Society of Transplantation and Cell Therapy, NMDP, and CIBMTR have been critical in giving us guidance.

Even in our own transplant setting, we are thinking about patients who are ultra‑high risk. Patients with high risk leukemias that are in second complete remission or MRD‑positive disease, we are trying to keep them on track the best we can.

There are some patients who have MDS, but not that high‑risk MDS, where we can buy a few more months with hypomethylating agent. Those transplants, we are trying to delay. At least in Wisconsin, our plan is to delay them through the June/July timeframe, and then bring them back on track.

The big aspect is, obviously, cell therapies. Most patients who need FDA‑approved qualities of life therapies are diffuse large B‑cell lymphoma patients. They are our very sick patients with active cancers.

CAR T‑cells, we are still keeping those patients on track. So far all the commercially approved CAR T‑cell products, the manufacturers, and the sponsors are still able to procure those products, transfect them, and transport them back to transplant facilities. Those activities are happening.

There are many clinical trials with cell therapies in patients with other lymphomas, myelomas, or solid tumors.

In our institution, we voluntarily put most of those trials on hold because most of our clinical research staff is working from home, so we don't have the capacity to enroll a lot of patients on clinical trials, which is concerning from a medical standpoint because for many patients who get on these cell therapy trials, that cell therapy trial may be their more realistic hope of getting a durable response out.

It's not true only for cell therapy trials. There are many patients who would otherwise be enrolled on trials with novel targeted agents for cancers or lymphomas. In our center we have limited capability to enroll those patients on such trials, and that is true for many centers across the country.

This pandemic really has implications far beyond what we initially thought. It's impacting every way we practice medicine.

What we have learned about cancer care during this epidemic, personally, is value of team care and a team‑based approach to taking care of cancer patients. In our program and many other programs in the country, we had to think on our feet, be flexible with our patient care.

From a transplant physician's perspective, we have to change how we transplanted patients. We had to learn to infuse a new type of graft.

In a way, we had to learn how to triage transplants very quickly. In our program, we do about 40 transplants a month. That was no longer feasible with the strain on the health resource system, so we had to learn very quickly which patients need to be offered treatment right now, because they desperately needed it, versus where we had wiggle room to delay care for a little bit.

It makes us think about access to therapy, as well, because I'm thinking about ‑‑ and it's going to happen to some of patients, unfortunately, in the near term ‑‑ is lots of our patients are working or they depend on insurances of their significant others.

What really bothers me right now is that see that happening in the future, is that some of our patients, because their spouses are no longer working, maybe they're no longer working, or the business they were a part of is no longer operational, may lose their health insurance. They might not have access to healthcare because of loss of coverage in the short‑term future.

I hope if one thing good comes out of this epidemic is we, as a nation, think about these things proactively, and we think about healthcare as a right, not as a privilege. I really wish and hope that that may be a silver lining out of this epidemic.

When we think about what long‑term consequences COVID will have on cancer care, it's a difficult question to address. We don't have any, obviously, no data available right now.

COVID is definitely changing the way we are approaching some of our patients. One impact that may happen in long‑term care of oncology patients ‑‑ and may not be just oncology, it may be other fields of medicine ‑‑ is integration of telemedicine into our practice.

In our program, like most programs, most of our patient follow‑up visits were based on face‑to‑face, in‑person visits. Within our system, we rapidly evolved to do phone visits, and within a month, we evolved to do video visits with our patients.

That sort of an encounter is not ideal for all patients. I strongly believe that an early post‑transplant or an early CAR T patient should be seen in‑person, and that's what I'm encouraging in our transplant program, as well, right now, but a lymphoma patient who is two, three years post‑therapy and is doing well can arguably be seen in a remote setting.

Early medicine, either in the form of a phone visit or in the form of a video visit, will be a bigger part of our care in the coming years.

The other aspect is how would COVID impact patient survival outcomes. We have survival outcomes available in more clear forms for certain diseases and in less clear forms for other diseases.

Good example is, again, transplantation. Transplant center outcomes are published every year through the CIBMTR "Centers Outcome Analysis."

Within CIBMTR, we are very concerned and very cognizant about what impact COVID will have on survival outcomes of transplant patients, because realistically even patients who have already gotten their transplant right now are not followed exactly the way we would have followed those patients if COVID‑19 didn't exist.

If I was seeing a patient every other week, right now, because of our limited ability, we may be seeing those patients less often. It is plausible that those patients may develop complications during those longer intervals of follow‑up and may present down the road with more advanced complications, like more advanced CMV disease or more advanced [inaudible 11:36] disease that may indirectly affect transplantation outcomes.

The other thing that in our lymphoma practice we are sometimes doing is, since we are, again, strapped for resources, we have many patients who are getting consolidation‑type therapies. Rituximab maybe for a Hodgkin patient after transplant or rituximab maintenance. Depending on our patient volumes, we are sometimes omitting those treatments after discussing the pros and cons with the patient.

Whether reduction in such therapies for lymphoma patients will have a long‑term impact on their survival outcomes is a good research question. Maintenance therapies are part of solid tumors, are part of other hematological malignancies. In that way, COVID can impact those outcomes.

I don't know whether this virus has any oncogenic potential. With long‑term follow‑up, we will realize that coronaviruses as a group have no data to suggest that they have any oncogenic potential. That's another thing that we may learn in the long term about this virus.

It is definitely a frightening time for the patients and, as a physician, a learning environment.

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