DNA Testing After a Stem Cell Transplant: a Fascinating Case

When you have an allogeneic bone marrow or stem cell transplant, the blood-producing cells in your bone marrow are killed off by radiation or chemotherapy and then replaced with functioning cells from another person. The technical term for this process is allogeneic hematopoietic cell transplantation

In allogeneic transplants, DNA from your “donor” (the person donating the replacement cells to you) travels along inside the cells that get transplanted, and you become a chimera at that point. (A transplant with your own cells is called an autologous ["self proportion"] transplant and does not affect your DNA makeup). After a donor’s cell take root in your body, you now have two separate sets of DNA represented in your tissues. Which results come back when you have a DNA test after your transplant depends on which cells get tested. The complexity of this situation makes it easy to understand how this has become the storyline of more than one crime scene investigation show on TV!

This type of acquired chimerism is distinct from the rare form chimerism present at birth -- congenital chimerism. Congenital chimerism happens when someone is born already having two distinct sets of DNA. It is thought to be caused by fraternal twin embryos joining early on in pregnancy to form one person. In a way, it is the inverse of identical twinning, when one egg splits into two. Congenital chimerism has only been documented in a few cases including the well-publicized case of Lydia Fairchild and one case I was involved in professionally just a few years ago, described in this Time magazine article here.

Acquired chimerism is growing more and more common with stem cell transplants being an available treatment for a number of conditions like lymphoma, leukemia, and sickle cell disease. Some hypothesize that the rise in fertility treatments for pregnancy conception might also be increasing the number of individuals born with congenital chimerism (due to increased twinning rates at conception); however, this theory has yet to be studied and tested.

Doing DNA testing on people who have already had a stem cell or bone marrow transplant can get tricky. Because there is interaction between the blood stream and types of cells lining the cheeks and because cells from your blood stream can get into your saliva, we actually can find both sets of DNA when we do a test on saliva or a cheek swab. Per multiple testing companies, this often causes the test to result in “failure” for many people who have been through a transplant. 

Here's what 23andMe wrote in response to a customer question on the topic:

"If you have received a bone marrow transplant, we cannot recommend that you use the 23andMe® Personal Genetic Service (Ancestry Service or Health & Ancestry Service).
The saliva sample required to receive the 23andMe Personal Genetic Service includes DNA from multiple cell sources, including epithelial cells from your cheeks and mouth and white blood cells from your saliva. As a bone marrow recipient, your blood cells will contain the DNA from your marrow donor, while your epithelial cells contain your own DNA. The combination of DNA sources frequently results in analysis failure. In the event that the analysis was successful, it still would be unclear whether the results were based on DNA from you or from your donor."

What I recently learned is that in some cases, the sample doesn’t fail! I had a gentleman ("Tom") reach out to me who had tested both prior to and after his stem cell transplant. When he took the raw data from his pre- and post-transplant DNA tests to the website GEDmatch.com and ran analysis of his DNA against other people in his family, the results were surprising. And yet, knowing the history of his transplant and who in his family was his donor, the results were not surprising. They actually made a lot of sense!

I am going to show you how this gentleman matched two people in his family along chromosome number 1, and I want you to guess which family member -- his sister or his son -- was his stem cell donor. 

If you are new to learning about GEDmatch, this is going to be more challenging for you! But hang around and give it a try. You might be able to figure it out even if you’ve never used GEDmatch before.

Tom and his sister before the transplant

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Tom and his sister after the transplant

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Tom and his son before the transplant

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Tom and his son after the transplant

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Here's a key to understanding the color coding in GEDmatch:

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Did you figure it out?

Tom’s sister was his donor! So now Tom is a chimera, with some of the DNA he was born with and his own sister’s DNA present in some of his cells. All that we see in his raw data file now, however, is his sister's DNA.

Tom was happy to share his story but has a word of advice:

If I had one thing to tell people going through a transplant, it would be to have a DNA test done prior to the transplant for history’s sake.

If you wait until after a transplant and then try to do a DNA test like 23andMe or AncestryDNA, you might forever lose the opportunity to have a true reflection of the DNA you were born with. This also means you may lose out on the opportunity to explore how your DNA matches other people, including your children, siblings, and future generations. 

Thanks for sharing your story and your images for the benefit of my readers, Tom! I am so glad your transplant was a success and wish you many healthy, happy years ahead.