Beyond Remission: Recognizing and Managing New Cancer Risks

Moderator: Good afternoon. Welcome to the workshop Beyond Remission, Recognizing and Managing New Cancer Risks.  My name is Marla, and I will be your moderator this afternoon.

It is my pleasure to introduce today's speaker, Dr. Kapil Meleveedu. Dr. Meleveedu is an Assistant Professor of Medicine, the head of malignant hematology, and medical director of the Blood and Marrow Transplantation and Cellular Therapy Program at the NEAG Comprehensive Cancer Center at the University of Connecticut Health. His clinical focus is on acute leukemias, secondary therapy-related leukemia, myeloid disorders, stem cell transplantation, and immunotherapy.

Please join me in welcoming Dr. Meleveedu.

[00:56] Dr. Meleveedu: Thank you very much, Marla, for that kind introduction, and good afternoon, everyone. Thank you for tuning in on a Sunday afternoon for this excellent symposium that BMT InfoNet has put together. I'm truly honored here to be part of a great, incredible line of speakers.

Today, we'll be talking about recognizing and managing new cancer risks after transplant and CAR T-cell therapy. The idea of this talk is to empower survivors through knowledge.

[01:45] We all know that transplant and cell therapies, especially CAR-T, are life-saving and curative treatments that have significantly changed the landscape of treatment options in hematologic malignancies, and the outcomes have been amazing. But like all powerful treatments, they do have some long-term side effects, including some small increased risk of cancer.

At this symposium, we are celebrating a second chance at life. So, the idea is not to instill fear, because the word cancer itself creates anxiety and fear for survivors, but to really empower you. When I say you, this includes all the survivors, some of the loved ones who have tuned into this talk, or people who are anticipating a transplant or CAR T-cell therapy as part of their journey.

[02:46] This presentation shares information to empower you, because we can detect cancer early. We can treat it promptly if you detect it early. And there are a lot of healthy things a person can do on their own that can actually help make a real difference in overall outcomes.

[03:06] So this is the overview of what we'll talk about today.

In the first 10 slides, I'm going to cover how common secondary cancers are and their incidence.

And then we'll cover why they happen. What are the mechanisms that result in those cancers coming back or different cancers happening?

And then we'll talk about screening. How do we identify the symptoms, or what are the signs that we can look for to find these cancers?

And then we'll talk about long-term follow-up and survivorship care plans.

Finally, the risk mitigation strategies and healthy habits and empowerment, where we'll focus on what strategies we have and what healthy habits one can pursue to decrease the risk of secondary cancers, and how to live well after transplant.

 So let's start with some good news.

[04:04] Transplant and CAR T-cell therapy (CAR-T) have increased the survival of patients with malignancies over the past two decades.

In fact, CAR-T has been called the most significant advance in 20+ years, and has shown the first overall survival benefit, especially in refractory large B-cell lymphomas.

CAR-T is now being offered in multiple myeloma and refractory B-cell acute lymphoblastic leukemia. We're talking about secondary cancers today because these therapies work, and more survivors are living long enough that long-term care is important. That's precisely the reason we are discussing this topic today.

So, let's understand the basics.

[04:50] What are secondary cancers?

These are not the return of the original cancer, which often is the focus of post-transplant care in the first few years, looking for whether the cancer is coming back, whether the patient has relapsed. That is NOT what we're focusing on.

We're focusing on new cancers that generally develop many years after transplant, after people have gone through their immediate post-transplant course.

It is really important to be aware of this cancer risk so that we can do something to prevent these cancers and detect them early.

The secondary cancer risk depends on whether one got CAR- T, an autologous transplant, which is a transplant with your own cells, or an allogeneic transplant, which is a donor cell transplant.

On the next slide, I'll cover these three broad categories.

[05:52] Therapy-related cancers seem to occur mostly after autologous transplants, sometimes also after CAR T. These seem to be caused by prior chemotherapy.

A lot of patients who need an autologous transplant had chemotherapy or radiation before, and that seems to be a risk factor that predisposes them to developing a blood cancer down the road. It can present itself as a condition called myelodysplastic syndrome or acute myeloid leukemia.

[06:31] The second bucket of secondary cancers is something similar to a lymphoma that happens after an allogeneic stem cell transplant. It is called post-transplant lymphoproliferative disorder (PTLD). It’s very treatable, and it's usually a virus that drives it.

The third bucket is solid tumors, which are basically skin, breast, and lung cancers. They can occur after both allogeneic and autologous transplants, as well as after CAR-T. Many are curable if caught early.

So, let's look at the broader context to put these numbers into perspective.

[07:15] In 2009, researchers looked back at almost 28,000 transplants to quantify the risk of developing a new cancer in patients who had a donor transplant (an allogeneic transplant)  compared to the general population. They found that patients had about twice the risk, compared to the general population, of developing a new cancer after an allogeneic transplant. And that was mostly for solid tumors. As you can see, over a period of 10 to 15 years, the incidence was at 4% or 5%.

[07:58] Now, the good news is that after an autologous transplant, data show that most survivors do not have a higher risk than the general population of developing a new cancer, except for a very small subset, 2% at a 10-year mark, who develop these therapy-related blood cancers (myelodysplastic syndrome, MDS or acute myeloid leukemia, AML).

[08:17] This slide shows new 2025 data from the Fred Hutch Cancer Center that looked at their own survivors 2 years after an allogeneic transplant. The risk of secondary cancers was about 5%. But the key takeaway is that the large majority of transplant survivors will not develop a secondary cancer.

All right, so let's break it down further within the solid tumor category. I think people may want to know what the numbers and the study show, based on key published data points.

You can see that there is a much higher risk for skin and oral cavity cancer after an allogeneic transplant than for other solid tumor cancers. To some extent, this has to do with chronic graft-versus-host disease (GVHD). So, people who have chronic GVHD seem to have a higher risk.

Similarly, you can see solid tumors of the breast and lung. As you know, there are risk factors already in there. A female who has had radiation to the chest is at increased risk of breast cancer, and smoking clearly increases the risk of lung cancer. 

[09:48] How about autologous transplants? The risks seem to be only marginally higher than those of the general population. In fact, for patients with myeloma, which is the most common reason for someone to undergo an autologous transplant, data show that the survivors do NOT have a higher cancer risk than the general population.

So, as we move CAR T-cell therapy up earlier in the line of therapies we give patients, we hope that people will have less exposure to chemotherapy or radiation, and their new cancer risk will be even lower.

[10:26] But how about CAR-T? CAR-T is the new kid on the block and has had tremendous success.

This was a landmark meta-analysis by Dr. Rajewski and his group, in which they examined data from 5,500 patients. They did a systematic review and found that the risk of new cancers after CAR-T was approximately 6% at two years.

The most common types of cancers seen were solid tumors and blood cancers. This was probably related to their baseline risk because of earlier exposure to chemotherapy and radiation. Initially, CAR-T was only approved as a fourth-line therapy or for refractory disease, so a lot of patients had to receive multiple rounds of chemotherapy before they were allowed to have CAR-T.

[11:17] So, the real question was, did CAR-T itself cause an increased risk of cancer? And when they tried to look for specific T-cell malignancies, because that was the biggest concern, you can see, the numbers were minuscule, like 5 out of 5,500 or 1 in 1,000 people. So, clearly, the benefits of CAR-T outweigh the risks, and this does not mean that CAR-T is unsafe.

But because they saw a signal, the FDA issued a warning that we might need to follow every patient for 15 years. That's mandatory now. The idea is to follow more patients to better understand their risk.

There was a subset analysis of four clinical trials. And when they looked at those who received CAR-T and those who did not, they found that the rate of secondary cancers was similar. It is very reassuring to know that post-CAR-T, the cancer risk, so far, does not seem to be different from the standard of care.

[12:19] So what are the risks of  NOT getting these therapies? Because perspective is very important, right?

It used to be that for relapsed refractory blood cancers, if you were not going to get CAR T or transplant, the median survival was low - six to 12 months. Most of the mortality was from the disease itself, and patients’ quality of life progressively declined, resulting in a poor prognosis.

Now, with a lot of these curative therapies, people clearly are living longer. And as you can see on the right, there is still some risk of a secondary cancer, but the risks are small, and we're quantifying it in terms of a decade now, 10 to 15 years of risk, so a dramatic improvement in long-term survival.

So, knowledge is important. Recognizing the risk is important. Understanding more about it is important. That's what we're having with this discussion.

Let’s focus on why these secondary cancers happen.

[13:30] Overall, there are five different ways that a cancer may happen after these therapies. 

One is due to DNA damage. The second appears to be due to immunosuppression. The third is a process in which bone marrow stem cells develop mutations, a natural part of aging, called clonal hematopoiesis, that can accelerate when somebody needs an autologous transplant or CAR T-cell therapy. And then there's virus reactivation and chronic inflammation.

[14:05] Why is it important for us to know, or at least understand these mechanisms?

Because understanding the why really helps us to know where to look. And once you know where to look, we know what to do about it.

So that's why I'm going to cover why these cancers happen, or what the potential mechanisms are, in the next few slides.

First, DNA damage. Chemo and radiation are designed to damage the cancer cells’ DNA. That's how the cancer cells get killed. Unfortunately, this sometimes also affects healthy cells’ DNA, but most healthy cells can repair the damage successfully.

Occasionally, this repair is imperfect, and some mutations may remain, which, over time, may develop into a blood cancer.

[14:51] How about the second mechanism of immune suppression?

This happens because the immune system's security guard is off duty. That's how I try to think about it.

In allogeneic transplants, for example, you need to put patients on immunosuppressive medications to prevent graft-versus-host disease (GVHD) or treat it. This can impair the immune system's surveillance capability, and a virus that is dormant in the body may reactivate.

One of the most common viruses that reactivate is the Epstein-Barr virus. This is the mono virus. Kids and adolescents carry this virus, and 90% of adults carry it, but it is usually dormant.

When somebody goes through an allogeneic transplant and is on immunosuppression, this can reactivate the virus and cause a B-cell-driven process, which can present like a lymphoma.

But the good news is that the risk drops significantly once the immune system recovers in the first two years, and it's very treatable. The monoclonal antibody rituximab has been around for 20-plus years now, and it treats the virus very well.

The other virus that may occur is the human papillomavirus (HPV), also driven by immune-driven processes.

[16:19] How about inflammation? Inflammation is a known risk factor because when the body perceives tissue damage, it attempts to control that. So, more cells need to go to the sites of inflammation to repair the damage.

Now, our human body is amazing. There are billions of cells that do this continuous work normally, even if you don't have inflammation, because they’re trying to protect your body.

If you have inflammation, there's more cell turnover and a higher chance that DNA errors can result in a mutation, which can eventually result in cancer.

As you can see (the numbers may be concerning), the incidence of skin and oral cancers is much higher than seen in the general population. This seems to pertain to people who have concurrent GVHD.

[17:58] Skin and oral exams or surveillance are critically important parts of survivorship and follow-up because when you can detect these cancers early, you can treat them. You do not need to go through extensive therapies to get rid of these early skin cancers, so recognizing this is important.

But inflammation seems to be the reason why these cancers are seen at a higher incidence in patients with chronic GVHD. 

The incidence of GVHD seems to be decreasing with improved donor selection and prophylaxis (prevention) strategies. These are retrospective data from a decade or more ago, so, I don't know if this risk will be the same going forward, but I remain hopeful that, with all the advances we're seeing, it will actually be much lower.

[18:23] What are the factors that increase YOUR cancer risk?

So, what I tell my patients is that it's important that we focus our energy and attention on things we can control. They do make a real, measurable difference.

So focus your attention on the right side of the screen in green, because the ones on the left side are factors that, unfortunately, one cannot change: when you get your transplant: what kind of transplant or CAR T you receive, what the chemo dose is, what's the radiation dose, what's the donor type.

Unfortunately, that is not something one can control. We have to work with what's available, what's best. We try to choose the best for our patients, but as a patient, there’s not much you can control.

[19:14] But there are a lot of things that you can see on the right, that you can control, that eventually matter. They make a real difference in preventing cancers down the road and in identifying these cancers and treating them. So really, I strongly encourage people to focus on that side of the slide.

On the next few slides, I want to cover how we identify these cancers, which is very important.

Many symptoms of cancer can also have benign causes. So persistent exhaustion, tiredness, maybe some confusion, weight loss, skin changes - these are very common symptoms- but they do not necessarily mean that there's a cancer happening. But being aware of these symptoms helps you report them promptly to your care team, who can look into them, and if there is cancer, do something about it early.

It’s important to stress that these are long-term symptoms that I'm talking about. People who have undergone CAR-T or transplant, especially an allogeneic transplant, may have a lot of the symptoms on this slide for the first few months or years. These are sometimes related to an infection, graft-versus-host disease, or just the transplant itself. These are not the symptoms I am talking about. I’m talking about seeing these symptoms after people got better, got back to their baseline, and are living their normal life, and then many years later seeing some of these new symptoms. You do need to pay attention to this.

[20:59] Is there something you can do to examine yourself and catch some of these symptoms early? Absolutely yes.  And that pertains to skin and also breast exams. 

So, skin is the first one on this slide. This is a simple check. We call it the ABCDEs of melanoma detection. Once a month, you need to examine your skin. Most people think they are aware of changes because they look at themselves in the shower, you know, or in the mirror. But pay attention to a few areas that you're not normally used to looking at, such as the back. You might need a partner or a friend to look at it.

Check the scalp. You have hair growing back now, and there's no reason to look inside the hair at the scalp, but it's an important area to check, or somebody could help you check it.

Look between the toenails and under the nails for any nail changes. What we're looking for is any lesion that looks irregular, has different colors within one lesion, or is a little bigger than a pencil eraser. If it changes in color, size, or shape, you need to alert your team or go to a dermatologist.

But even then, despite all that, you still have to see a dermatologist at least once a year because skin cancers seem to be aggressive in survivors who have undergone transplant or CAR T, but they can be very easily treated. Most of these are superficial skin cancers. If you detect it early, you can burn it or cut it out. You don't need more aggressive therapies than that.

So detection is key, and skin cancers are an important part of survivorship surveillance.

[22:47] How about breast exams? A clinical breast exam every one to three years is similar to what is recommended for average-risk women.

But if somebody needed a transplant younger than age 30 or if they needed radiation before the transplant, the screening starts early, which includes annual mammograms plus MRIs.

There are very clear guidelines on this, which I'll show on the next slide.

[23:13] There are things that you might need help from a physician's office to do, beyond the physical exam that you can do on yourself.

People need colonoscopies and low-dose chest CTs, and these guidelines are updated every few years. The National Marrow Donor Program, or NMDP, updated these guidelines in 2026, and they look pretty similar to what we have on this slide.

[23:44] So, is there a survivorship model for CAR T?

That's a common question that's being raised in the field now. Fortunately, there was a publication in the Journal of Clinical Oncology in February 2026, which looked at this particular question and recommended cancer screening for CAR T survivors. And as you can see, the theme is very similar to a transplant patient or a survivor.

As we continue to learn more about CAR-T, I think the focus will likely also differ depending on who within the CAR-T group requires special surveillance and who within the transplant group does. One surveillance model may not fit all, as we learn more about it.

For example,  GVHD patients may need more focus on the skin, the mucosa, and the oral cavity, as well as genital area surveillance, whereas young people who had radiation may need more long-term follow-up for solid cancers. 

Somebody who had heavy therapy for lymphoma or myeloma before transplant or CAR-T might need to think more about blood cancer surveillance. Somebody who has worsening cytopenias or low blood counts beyond the expected window, usually 90 days after CAR T, may need to consider having a bone marrow biopsy to make sure there's nothing else you're missing.

So, there are some nuances, but overall, the idea of surveillance seems to be the same.

[25:30] Why is screening long-term surveillance important? Because the risk of secondary cancer, unfortunately, does not go away. In fact, some of the late deaths after transplant or CAR-T may be due to a secondary cancer. 

But the good news is that early detection dramatically improved outcomes. 

Annual checkups with your transplant team are recommended. These are really tune-ups for your health, making sure everything is running smoothly and that your organ systems are comprehensively evaluated.

[26:10] Every survivor should have a survivorship care plan. This is the health roadmap. If you don't have one, definitely go back and ask your team for one.

A survivorship care plan is usually put in place after 100 days for autologous transplant and CAR-T's, but it may be more like one year or beyond after an allogeneic transplant. That's because much more intensive follow-up is already in place during the first many months or the first year of allogeneic transplant, where we are focused on looking for GVHD and other complications. 

A survivorship care plan is beyond that phase for many, many years, pretty much the rest of your life.

If you don't have a survivorship care plan, there are a lot of resources, including BMT InfoNet, NMDP, and your transplant center.

Sometimes people get transplanted out of state, and their survivorship care is transferred to where they live. Sometimes people just move from coast to coast. So having this survivorship document helps.

I have a cheat sheet at the end of these slides, which you can download, print out, and put in your wallet, that gives you an idea of what treatments you underwent, which would help anywhere you travel or go.

[27:34] Let's focus on what we can do to mitigate the risk of secondary cancers.

It’s a multi-pronged approach for long-term health, not just cancer, because a lot of these interventions really help overall health, be it cardiovascular health, bone health, or endocrinological issues that may pop up. It really helps a lot.

The first four you can see at the top are things a survivor or anyone can do themselves, whereas the bottom four are things you might need professional help for, but showing up for appointments is the first step. You do have to show up for these appointments. These are all backed by real evidence, which we'll cover in the next slides.

[28:24] First and foremost, your single best action is to stop smoking.

Smoking really has a strong association with cancer, especially in terms of CAR-T or allogeneic transplant, because you may have received radiation or TBI, which increases the risk for cancers in the solid organs, especially the lung.

It has been shown that not just lung cancer, but oral cancer, bladder cancer, and heart are much more common in people who continue to smoke after transplant or CAR T. So, if you do one thing after this talk, please pay attention to this concern.

This is a challenge for many people. There are many cessation programs. There’s a lot of medication, counseling help, and peer support that you can have. Definitely, know that you're not alone in this.

You don't have to feel guilty that somebody can’t quit, but it sometimes takes a lot of effort to help you get there. But acknowledging that we need to stop smoking is the first thing that a person can do from their end. That's the biggest strategy, number one.

[29:34] How about sun protection? A dermatology visit is important, as well as self-exams; remember the ABCDs are critically important.

There are data-driven recommendations to use sunscreen and protective clothing, especially if you'll be exposed to the sun for a long time. A few minutes of sun protection really helps prevent one of the most common secondary cancers, which are skin cancers, that can be treated very effectively early on.

[30:17] How about diet, weight, and physical activity?

I think the world in general has been very aware of the benefits and the downside of these modalities.

In the context of cancer, there's data that increased weight or obesity increases the risk of breast cancer and colorectal cancer.

So, it is important to recognize that it is important to follow through with a dietitian or any other program that you're part of to help you keep healthy.

And that's the same for physical activity where the evidence is very clear.

[30:58] There is clear data that vaccine protocols are important for preventing some virus-related cancers. This is important because, especially after an allogeneic transplant or CAR T, the immune system is reset. The previous diseases, exposures, and vaccines that you had are usually wiped out.

So, you do need to get all those revaccinated, and vaccines are one of the easiest and most effective forms of cancer prevention.

Targeted screening. Beyond breast cancer screening that we talked about, there are very clear guidelines on colorectal cancer, lung cancer, thyroid cancer, and liver cancer.

The key is if anybody had abdominal radiation or a history of gut GVHD, they may be at a higher risk and might need to start colonoscopy screening earlier than the age of 45.

Screening catches lung cancer before it causes symptoms, when treatment is most effective. 

Lung cancer similarly has clearly documented guidelines. All these numbers are not that critical to go through. You'll get the slides after this talk, so you'll be able to look at them. But the idea is that screening before symptoms appear helps catch lung cancers. So that’s really important to keep that in mind.

The screening involves only low-dose CT, and some people wonder if is that more radiation exposure? It's not. There's data showing that ,the benefits of low-dose CT far outweigh the risks.

[32:56] Oral cancer. Dental visits at least twice yearly are very important, and there is a low threshold for a biopsy of any lesions. People with oral GVHD have a higher risk.

Similarly, pap tests for cervical screening, and blood work for liver cancer screening and iron overload.

[33:32] Last but not least: Do not forget your mental health.

I have had patients who are so anxious about cancer that they completely avoid screening, which really is the thing that helps the most.

Patients have shared with me that even when they drive around the center where they had their transplant, they get physical manifestations, including nausea and vomiting.  So, the challenge is real. The PTSD is real. The anxiety is real. But there are strategies that can help mitigate that anxiety beyond medications, such as peer support, exercise, and mindfulness.  So, it's not just medication that I'm talking about.

You do not want to miss screening windows and opportunities, since you could eliminate cancers if you catch them early.

[34:28] This is your own health journey. You are a survivor. You've survived one of the most powerful treatments in medicine. There is a risk of secondary cancer, but it's actually very small compared to the benefit.

For people who have gone through something as intense as a transplant and survivorship, maintaining their health probably is the least of the stressors that they have had to deal with, because going through that first phase of transplant itself is a lot.

Screening catches things early.

Healthy habits do make a difference, and knowledge makes you the most powerful member of your team.

[35:05] So, I wish you all the best. There are a few more slides. This is a resource I've put there. You can print it out, put it on your refrigerator, in your bedroom, or in your bathroom, wherever you see it most often. This is just a healthy habit checklist.

Here’s that card that I talked about, which you can print out, put in a wallet, and fill out based on what kind of transplants or CAR-T  you had.

And there are plenty of resources online, including BMT InfoNet, Blood Cancer United, and multiple transplant and CAR-T centers.

[35:35] These are all my references, and I'm happy to take any questions.

Question and Answer Session

[35:43] Moderator: Thank you, Dr. Meleveedu, for this excellent presentation. We will now begin the Q&A session.

[35:59] Is there anything I should do or not do if I have skin GVHD to prevent future skin cancers?

[36:14] Dr. Meleveedu: I think we covered this in some of the previous slides. Having skin GVHD does seem to increase the risk of skin cancer.

So, I would definitely advise you to do that monthly self-check of your skin, looking for any unusual-looking lesions, different-colored lesions, and anything that's growing or irregular, and bring it to the dermatologist's attention promptly.

Second, visit the dermatologist at least once a year, which is critical for everyone, to catch lesions early so they can be treated.

Talk to your transplant team. They'll be managing your graft-versus-host disease, and there might be opportunities to reduce or adjust immunosuppression based on how your chronic GVHD responds.

Fourth, but not least, are sun-protective measures.  Use a strong SPF 30+ sunscreen every day if you will be exposed to the sun or direct sunlight.

Long sleeves, clothing, if you can. That would be ideal.

And then, try to avoid being in the sun during the peak UV hours, which are 10 to 4. That's a long window. I wouldn't really say that there's a lot of data on that. But as much as you can, limit UV exposure, as that is another risk factor. 

So those are all the things one can do with existing skin GVHD to reduce the risk of skin cancer.

[37:57] Moderator: This person is struggling with severe oral GVHD one year after their transplant. Are they at a higher risk of oral cancer?

[38:11] Dr. Meleveedu: I think the first year after transplant is a short window for any cancer to happen. This talk is about cancer risks that are beyond the five to 10-year mark, for long-term survivors.

I'm sorry to hear that you are suffering from oral GVHD. Unfortunately, this is a real problem. Within the first two years after transplant, GVHD may become a problem, but there are many ways we can treat and control the risk of oral GVHD.

To answer your question, there is a higher risk of oral cancer down the road, but having said that, it's too early for us to really say because some people do get oral GVHD early on. So, if it gets controlled within the expected time frame – a year or so - if you're able to manage that, that itself might mitigate the risk of long-term oral cancer.

I strongly encourage having the dental visits. And since you're having active GVHD within a year of transplant, one thing you can do is to have a dental visit every six months rather than annually. That is a guideline. If somebody is considered at higher risk because they have active oral GVHD, they may have to see dentists a little bit more often.

If they see any lesions that do not look like GVHD and they're concerned, they will have a low threshold for sampling them to make sure they can catch and treat them.

I wish you good luck. I know oral GVHD is treatable. There are a lot of options. Hopefully, with time, that can be better managed.

[39:57] Moderator: When does a patient need to receive immunization post-transplant?

Dr. Meleveedu: Yes, this is a very important question. It’s something built into every transplant center's protocol: when and which vaccines one should receive.

There are national guidelines and papers from Dr. Majhail and from NMDP -the National Marrow Donor Program. They keep updating all these vaccine schedules.

Most centers start vaccines 4 to 6 months after transplant. Center-to-center, you might see some differences in vaccine schedules based on their individual institutional data, but most of them start around the six-month mark.

Also, it depends on what kind of transplant you had. Depending on whether you had an allogeneic transplant, an autologous transplant, or a CAR-T, the timing may be slightly different. The reason is that after an allogeneic stem cell transplant, one may still be on immunosuppression. One may still be experiencing some side effects, including GVHD. Some people are on what we call IVIG maintenance. So, there are differences in timing across those scenarios for when someone should get vaccinated and which vaccines they should receive.

Dead vaccines are usually the ones that people start with at the six-month mark, even after an allogeneic transplant. And live virus vaccines, like MMR, are the last. It might be even two years after the transplant. It is once people are off their immunosuppression that they get those vaccines.

So, the schedule usually runs from six months to two years, on average. And like I said, there may be some center-to-center differences, but everybody still gets everything covered.

[41:57] Moderator: This person wants to know if gut health is something they should be watching. Are colon cleanses good or bad?

Dr. Meleveedu: Gut health is absolutely important. I think there was a talk yesterday on gut microbiome. I would encourage this person to look into it and learn how the gut microbiome plays a role in preventing GVHD and other transplant complications. There's a lot of evolving data on that.

How we maintain gut integrity during transplant is a heavily researched topic.  There are no clear guidelines, yet, to my knowledge.

Regular cleansing isn't something I've seen much data on. There are good bacteria and bad bacteria in the gut. So, what the interplay is between the good and the bad bacteria when somebody goes through a transplant, and how to manipulate that so that we have more good bacteria that help prevent inflammation, infection, and graft-versus-host disease, is the real research question. 

I do not recommend colon cleansing strategies as a way to maintaining gut health. I'll be open to reviewing any of the literature, but for now, I'm not aware of anything that would be medically recommended.

[43:42] Moderator: Can you expand on CHIP and secondary cancers?

[43:54] Dr. Meleveedu: This is a very active area of research. CHIP means clonal hematopoiesis of indeterminate potential. I think I had one slide where I mentioned clonal hematopoiesis. That's the same idea as CHIP.

What this means is that as the bone marrow ages in everyone, there seem to be certain changes that happen in some normal cells, which help create a mutation. That seems to be part of normal aging. There is clear data that every decade of life beyond 60, 70, 80, the incidence of seeing these clonal mutations seems to be progressively higher. So, clearly, there's some indication that there are mutations there.

These mutations seem to have an impact not just on cancer but also on cardiovascular, bone, and gut health.

There are many research studies underway involving CHIP mutations. In fact, there are CHIP clinics at some institutions across the country analyzing what these mutations mean.

This is a question that was looked at in a Nature paper in 2025 in the context of an autologous transplant. What they were looking for was if a person had some of these chip mutations at baseline and undergoes high-dose chemotherapy and transplant, whether there is a risk that these mutations can progress to become a different cancer, like a blood cancer, or a new cancer down the road.

And there seems to be a signal, especially if it is something called a TP53 mutation. High-dose chemotherapy seems to select some of those clones. Often, these mutations are detected beforehand, leading to a discussion of the pros and cons of proceeding with a transplant. This is an active area of research.

Just the presence of a mutation or CHIP does not mean that everybody with that mutation will end up getting cancer. This was emphasized in that Nature paper from 2025. And that's because a person's immune system does still seem to have a role in preventing the CHIP from becoming a cancer in the future. So, there's an interplay between clinical and microenvironmental factors that seem to determine which kind of chip may become another future cancer.

So more to come, more to learn. We have limited data that, at least in the context of TP53,  we need to be a little more careful.

[46:52] Moderator: This person’s doctor told them that the guidelines for a Pap smear are every five years. Your slide indicates an annual Pap smear. Would it be enough to mention this person’s history of GVHD and bone marrow transplant to their gynecologist to increase the frequency of a Pap smear?

[47:15] Dr. Meleveedu: The frequency of pap smears is definitely changing. Whether you need more frequent Pap smears depends on whether you have high-risk disease and whether you have a risk of genital graft-versus-host disease, not just graft-versus-host disease of your skin or other areas. It would be important to have that conversation with the gynecologist, saying, "There is an increased risk factor. I probably need more frequent Pap smear testing than every five years.”

I do think that it is probably more frequent than five years. It should be at least every three years. Don't quote me on it. I'll have to review the guidelines again. I do think there is definitely room to discuss this with the gynecologist because genital GVHD increases the risk of cervical cancer and other cancers. So, it's important to stay on top of screening and catch these lesions very early.

I would have your transplant team or your transplant physician speak with the gynecologist, because they know your transplant history better. They know exactly what additional risk factors you have, based on the disease for which you were transplanted, and what your current GVHD status is. I think the conversation needs to happen between your transplant doctor and your gynecology team. It would be very meaningful to come to a consensus.

[48:45] Moderator: Is it possible to have GVHD after an autologous transplant? Have you ever seen cases when patients develop an autoimmune symptom similar to GVHD?

Dr. Meleveedu: I think this is a very, very challenging question for me to answer. The concept of GVHD, by definition, generally requires donor cells. That's what attacks or seems to attack the host tissue. That's the definition of graft-versus-host disease. It is really well described in the context of an allogeneic stem cell transplant, because that's where you use donor cells.

So, an autologous stem cell transplant, by definition, means we use our own cells from the body for the transplant. So, they shouldn't negatively react to your own tissues because they have been trained not to misbehave since birth. So, in my opinion, the concept of autologous-transplant-related GVHD is a misnomer, but you will see literature on it.

This is why I said it's a very difficult question to answer, because there is a concept out there in the literature that a small proportion of patients who have gut symptoms, especially GI symptoms, with voluminous diarrhea, have a biopsy that really looks like graft-versus-host disease, and they only had an autologous stem cell transplant. It is described, but there isn't much literature on it. There are really only isolated case reports or case data.

In fact, I have anecdotally experienced this during training at Mayo Clinic, seeing something similar to autologous GVHD. So yes, it's out there, but I would say the pathophysiology is not completely understood.

I do not think it is similar to the actual graft-versus-host disease that happens after allogeneic stem cell transplant. For me, I think it is an autoimmune phenomenon that happens may be unique, but it's not a graft-versus-host disease.

[51:12] Moderator: How much risk do maintenance drugs like Revlimid pose for secondary cancers? Does this risk increase or decrease as you continue taking the drug while in remission?

Dr. Meleveedu: Great question. Lenalidomide (Revlimid) has been associated with some risk of secondary malignancies. In fact, I  did a retrospective study looking at that particular question of whether autologous transplant or lenalidomide causes cancer. It was actually one of my colleagues who led the study, and I was part of it.

What we saw is that, yes, there's some risk, but it does not seem to be higher than the risk of the autologous transplant itself. 

There are more studies that have looked at whether being on something like lenalidomide maintenance long-term adds additional risk after transplant. The data continues to be conflicting, because many of the multiple myeloma patients would have had other alkylators or other DNA-damaging therapies, which seems to create a conflicting multifactorial result of whether the conditioning of the chemo, whether the other alkylators increased the risk of cancer, or was it lenalidomide itself.

This is an ongoing discussion in the myeloma community because it was initially thought to be two or three years of maintenance. But there are different maintenance agents now available, not just lenalidomide.

So, there is some risk, but it does not seem to outweigh the benefits of being maintained on Revlimid, as it has an overall survival benefit by preventing myeloma relapse. People live longer if they're on maintenance than if they're not. So, it's a risk-benefit discussion here. There seems to be a small risk, but the benefit seems to clearly outweigh the risk of that secondary malignancy.

[53:31] Moderator: How long after transplant would you expect to see symptoms of secondary cancer?

Dr. Meleveedu: I think I had that in some of the slides, but the symptoms that I listed there that are clues to help identify the secondary cancers are usually for the long-term.

When I say long-term, it's for many years after somebody has had a transplant, all their acute complications have subsided, and they're back to their baseline and continuing to live their life.  And then some of these symptoms happen. That's when you have to worry.

And of course, in between, you still need to notify your team about those symptoms, but they could just be from a post-transplant effect, GVHD, or medications as you're on.

A lot of the solid cancers, such as skin cancers, breast cancer, and lung cancer, tend to happen at an interval beyond five years, 10 years, 15 years down the road.

The therapy-related blood cancers, which are usually seen in people who had an autologous transplant or CAR-T and had been heavily pretreated for their original cancer, tend to happen in the first two to five years. So, the blood cancer risk seems to be different from the solid cancer risk. 

For the unique one in the middle, PTLD or post-transplant lymphoproliferative disorder, which is unique for allogeneic transplant patients, the risk is usually in the first two years.

So, these symptoms vary by cancer. The timeline seems to be different.

When we're talking about survivorship in general, I would say these are way beyond your immediate transplant phase, many years beyond your transplant phase.

[55:26] Moderator: Okay, that was excellent. On behalf of BMT InfoNet and our partners, thank you, Dr. Meleveedu, for an excellent and very helpful presentation. And thank you, the audience, for your questions.

[55:52] Dr. Meleveedu: Thank you very much for this opportunity. Thank you, BMT InfoNet and the team, for this opportunity to present this important and relevant topic to this community.