Stem Cell Transplants May Increase Risk Of Heart Disease
Results from a large, retrospective study conducted at City of Hope National Medical Center indicate that patients who receive stem cell transplants are at a higher risk of developing heart disease than the general population.
The researchers found that patients who underwent a donor transplant and developed graft-versus-host disease, a common transplant-related complication, were at the greatest risk of developing heart disease.
“Our findings show that the process of receiving a stem cell transplant alone increases a recipient’s risk of developing heart disease,” said the study’s lead investigator Dr. Saro Armenian from City of Hope in Duarte, California, in a press release. “However, the type of transplant and whether the recipient was treated for [graft-versus-host disease] can also increase that survivor’s heart disease risk,” he added.
The researchers believe that their data could be used to identify patients who have an increased risk for heart disease and therefore need close monitoring and management of the risk factors.
“The results of this study demonstrate the importance of intervention strategies that can help mitigate these modifiable heart disease risk factors in transplant recipients before and after transplant, and we hope they can serve as a basis for creating a predictive model to identify those patients at highest risk of developing heart disease,” said Dr. Armenian.
According to Dr. Armenian and his colleagues, heart disease is one of the leading causes of death after stem cell transplantation.
In the general population, high blood pressure, diabetes, and high cholesterol levels are risk factors that have been associated with the development of heart disease.
The researchers point out that patients receiving stem cell transplants may be at an increased risk of developing these risk factors because of the high-dose chemotherapy used during the procedure as well as the development of transplant-related complications.
Previous studies that sought to evaluate these heart disease risk factors in patients receiving stem cell transplants were limited by small patient populations and short follow-up times.
In order to more thoroughly assess the heart disease risk factors and development of heart disease in patients who received stem transplants, Dr. Armenian and his colleagues retrospectively analyzed data from 1,963 patients who received a stem cell transplant for a blood-related cancer at City of Hope between 1995 and 2004. Approximately 15 percent of the patients had multiple myeloma.
“Our study sought to better determine the specific factors before and after transplant that can lead to heart disease in a large group of transplant recipients,” said Dr. Armenian.
The median age at transplant was 44 years, and all patients survived for at least one year following the procedure.
Furthermore, 43 percent of patients received a donor (allogeneic) transplant. An allogeneic transplant involves transplanting a healthy donor’s stem cells into a patient after high-dose chemotherapy. However, multiple myeloma patients most often receive autologous stem cell transplants, in which the patients’ own stem cells are re-infused into their bodies after high-dose chemotherapy.
For the purposes of the study, heart disease risk factors included high blood pressure, diabetes, and high cholesterol levels. Heart disease was measured as the occurrence of heart failure, angina, heart attack, or stroke.
The median follow-up time was 5.9 years.
The researchers found that 36 percent of patients had high blood pressure after their transplant, of which approximately one half had the condition at the time of transplant, and the other half developed it after the transplant. The median time to post-transplant high blood pressure was 0.4 years.
In addition, 17 percent of patients had diabetes after their transplant, of which 55 percent developed the condition after the transplant. The median time to post-transplant diabetes was 1.9 years.
The most common heart disease risk factor was high cholesterol levels (44 percent of patients). Approximately half of the patients (57 percent ) developed this condition after the transplant in a median of 0.5 years.
The investigators also compared risk factors in patients receiving allogeneic versus autologous stem cell transplants. Overall, they found that patients who received allogeneic transplants developed heart disease risk factors significantly faster than those who had autologous transplants.
For instance, the median time to high blood pressure following transplantation was much shorter for allogeneic transplant recipients than for autologous transplant recipients (0.2 years versus 3.7 years).
This trend was also true for post-transplant diabetes (1.2 years versus 3.3 years) and high cholesterol levels (0.2 years versus 1.6 years).
The researchers found that patients who developed graft-versus-host disease after an allogeneic transplant were most vulnerable to heart disease. Graft-versus-host disease is a common allogeneic transplant-related complication in which the donor cells recognize the patient’s cells as “foreign” and attack them.
The results showed that 55 percent of these patients had high blood pressure, 26 percent had diabetes, and 53 percent had high cholesterol after their transplant.
Investigators also found that older age and obesity were significant predictors of these risk factors in transplant patients.
Ultimately, 6 percent of patients developed heart disease at a median of four years after transplant.
Patients who had more risk factors had a higher chance of developing heart disease (5 percent for none, 7 percent for one, and 11 percent for at least two risk factors).
For more information, please see the study in the journal Blood (abstract) and the American Society of Hematology press release.
Related Articles:
- Common Measures Of Heart And Blood Vessel Health May Predict Risk Of Heart-Related Side Effects During Treatment With Kyprolis
- Number And Type Of Stem Cell Transplants Carried Out Each Year For Multiple Myeloma Vary Markedly Across U.S. Cancer Centers
- Selective Digestive Decontamination May Reduce Risk of Infection In Myeloma Patients Undergoing Autologous Stem Cell Transplants
- Stem Cell Transplantation May Be Underutilized In Multiple Myeloma Patients In Their 80s
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
Two comments on the above:
1... it kind of makes sense, actually. After a stem cell transplant (I'm a bit over a year past mine) there is a significant decrease in physical activity. My guess is that the older you are the longer that state lasts.. and that state would contribute very significantly to the onset / increase of heart disease, would it not?
2... the article makes no mention of physical damage to the heart by simple brute force caused by the chemo (Melphalan) used pre-transplant. I wonder what percentage of folks have that heart damage? I do... I lost 20% function in my lower left ventricle. There, again, is a contributing factor to a more sedentary lifestyle (in my case very significantly so), which will as I contended above extrapolate to heart disease.
So, thanks, transplant. You temporarily stalled the cancer, but gave me a whole other set of issues... and now the race is on to see which will get me first, I guess?
I a wondering whether there is a correlation between having heart disease before transplant and a worsening of the condition after transplant. I have congestive heart failure yet am a candidate for transplant. Should I be?
I felt my blood pressure rise as I read this article reminding of the shadow issue of surviving multiple myeloma, high-dose melphalon, and transplant.
I was put on blood pressure medication during my treatment. A year after transplant, I tried going off with my doctor's approval...until I found myself in the ER one night thinking I was having a heart attack. I was not, but my blood pressure was off the charts. I went back on medicaion, though finding the right one was a trial and error process. The first one didn't work well enough. Another gave me a chronic cough. Now I'm on Diovan.
A report of this nature feels a bit unfair when there is no attention paid to how transplant patients can keep their hearts from deteriorating. We hear about the usual diet and exercise methods, but are the post-transplant heart issues somehow different? Is the damage a final sentence?
that is a very interesting study. I guess that in the future, with a lot of patients declining to have a stem cell transplant, there could be comparisons made within the MM patient group about heart health. my blood pressure also shot up to abnormally high levels for a few months after the ASCT, but is now back to my normal levels..on the low side. with the increased viscosity of my diseased blood, I must have been at risk for stroke or heart attack, but now back to my new normal not so much. one thing is for sure though, I make exercise a part of my day...usually walking a few clicks. an article like this confirms that to me as a priority. bTW, the year IWas diagnosed was a sad one...two male acquaintances both died of heart attacks. in one case, there was no warning. at least my life was spared
And I try just to live in a healthy way now (not that I wasn't trying before!)
@Pat P: I have a chronic cough as well... I thought I had no choice in the matter. It often ruins sleep for my wife and I. I am on Ramipril.
Well, I will certainly be taking this up with my doctors!
All of these drugs listed below which are used in high-dose chemotherapy are cardiotoxic. Stem cell transplants have nothing to do with this cardiotoxicity. It is the high doses of these drugs that proceed and necessitate stem cell salvage that are the culprits, without graft/host disease, which would only exacerbate the cardiotoxicity.
Daunorubicin (Cerubidine®)
Epirubicin (Ellence®)
Idarubicin (Idamycin®)
Cyclophosphamide (Cytoxan®)
Fluorouracil (5-FU)
Mitoxantrone (Novantrone®)
Cancer drugs that have been reported to cause abnormalities in heart rate or rhythm in more than 10% of patients include:
Arsenic trioxide (Trisenox®)
Daunorubicin (Cerubidine®)
Denileukin diftitox (Ontak®)
Gemtuzumab ozogamicin (Mylotarg®)
Idarubicin (Idamycin®)
Melphalan (Alkeran®)
Octreotide (Sandostatin®)
Oprevelkin (Neumega®)
Paclitaxel (Taxol®)
Tretinoin (Vesanoid®)
@Snip - You said "I have a chronic cough as well" and then mention that you are taking ramipril ... The cough is probably due to the ramipril. A dry cough is a frequent side effect of ramipril and other drugs in the same class as ramipril, so-called "ACE inhibitors". As the Wikipedia article on ACE inhibitors explains,
"A persistent dry cough is a relatively common adverse effect believed to be associated with the increases in bradykinin levels produced by ACE inhibitors, although the role of bradykinin in producing these symptoms remains disputed by some authors."
More generally about this study, the results aren't likely to be too surprising to myeloma specialists given -- as suzierose points out -- that the drugs used during the high-dose chemotherapy phase of the "transplant" process are known to have cardiac side effects.
The unfortunate thing about this study, however, is that it doesn't answer key questions like: What would have happened to the patients in the study if they hadn't had a stem cell transplant? If the patients who had transplants had, instead, had different therapy, how much better would their cardiac health have been?
These aren't just rhetorical questions. Remember how, before Kyprolis was approved this summer, the FDA was concerned about the number of heart-related deaths during Kyprolis's clinical trials? Almost a quarter of the patients in the Kyprolis trials the FDA reviewed before the drug was approved had heart-related side effects.
I'm not disputing that transplants create cardiac issues. They do. But so do other myeloma treatment options.
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