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From the JAMA Network, this is JAMA Clinical Reviews, interviews and ideas about innovations in medicine, science, and clinical practice. Hello, and welcome to our listeners around the world. I'm Dr. Kristen Walter, Deputy Editor at JAMA.
I'm joined today by Dr. Harami Amonu, who is Associate Professor at Harvard Medical School and a Physician Scientist in the Department of Psychiatry at the Brigham and Women's Hospital in Boston and in the Department of Supportive Oncology at the Dana-Farber Cancer Institute. Today we will be discussing a JAMA Insights article titled Allogeneic Stem Cell Donation, which Dr. Amonu co-authored with Dr. Heather Stavansky and Dr. Benjamin Brewer.
This article was published online on December 11th. Welcome, Hermie. Thank you, Dr. Walter. Hematopoietic stem cell transplantation can be a life-saving therapy. Can you describe the conditions that are most commonly treated with stem cell transplantation?
Yes. So stem cell transplantation has become a potentially life-saving therapy for thousands of patients who have different hematologic and bone marrow cancers. So these include things like leukemia, lymphoma, multiple myeloma, or myelodysplastic syndrome.
It's also a potentially life-saving therapy for patients who have non-malignant conditions such as sickle cell disease and aplastic anemia. And this is for both adults and children. And can you explain the difference between autologous and allogeneic stem cell transplants and how commonly are they performed in the U.S.?
Yeah, so autologous stem cell transplants involve transplantation of a patient's own stem cells, whilst allogeneic stem cell transplantation involves the transplantation of stem cells from a related or unrelated donor.
And based on data that we have from the Center for Interventional Blood and Marrow Transplants Research, approximately 20,000 stem cell transplants are performed in the U.S. in 2023. And of these, a little over 11,000 were for autologous stem cell transplants, while over 8,000 were for allogeneic stem cell transplants.
For allogeneic stem cell transplants, selecting an appropriate donor depends upon typing of human leukocyte antigen, or HLA, genes, and matched sibling donors are the ideal source for allogeneic stem cell transplants. Can you tell us what percent of patients in the U.S. have such a donor and what the options are for those who don't have a matched sibling donor? Yes, so as you indicated,
Match sibling donors are the ideal donor for people getting allogeneic stem cell transplants. But unfortunately, only 30% of our patients have such a donor. And so for the remaining 70% of patients, we have to look at alternative sources of stem cells.
including HLA-matched and related donors, which accounts for about 45%. And then other donor sources include haploidentical donor sources, which are related donors in which the HLA of the donor cells match half of the HLA in the recipients.
And then we also have 20% receiving much-related donor stem cells. And then lastly, another small proportion of our donors are from umbilical cord blood stem cells of unrelated donors.
So allogeneic stem cell transplants, as you sort of alluded to, can be performed using peripheral blood stem cells or stem cells obtained from the bone marrow or umbilical cord. Which of these sources is most commonly used for stem cell donation in the U.S., and which factors go into making this decision?
So a lot of the stem cells that we use in the U.S., as you indicated, are from peripheral blood stem cells or stem cells that are obtained from the bone marrow or umbilical cord blood. Clinicians make these decisions about the appropriate donor and type of stem cells used based on factors such as the donor age, the patient's age, the type of disease that we are looking to treat, and also patient preference.
And which is the most common source in the U.S. currently? So in the U.S., about 85% of allogeneic stem cell transplants are from peripheral blood stem cells. And although bone marrow stem cells are preferred for pediatric patients because they are associated with like a decreased risk of a major complication of allogeneic stem cell transplants, which is Grapp-versus-host disease.
And once a potential stem cell donor has been identified, what type of assessment do they undergo to determine if they will be a suitable donor? Before someone is a donor for stem cells, there are a lot of assessments that are done. Some of them are physical assessments to assess different risks of infectious disease, such as AIDS, syphilis, and Chagas disease, which are transmissible through the stem cell transplantation.
Donors are also tested for infectious disease markers such as hepatitis C virus antibody, cytomegalovirus total antibody, and human immunodeficiency virus prior to transplant. After a patient has cleared the pre-donation assessment, how are their stem cells mobilized and obtained?
So there are a few considerations for mobilizing stem cells. And the stem cell mobilization usually happens after donors receive five days of a granulocyte colony stimulating factor, or GCSF, prior to apheresis, which is a separation of the donor blood cell components at a blood collection center.
And then when we think about bone marrow harvest, those are performed in an operating room, typically with general anesthesia, where a bone marrow procurement happens from a donor's posterior iliac spine. And let's move on to the potential effects of stem cell donation on the donor. What are some potential adverse effects of peripheral blood stem cell donation and bone marrow harvest? And how long do these adverse events typically last?
Yeah, so for peripheral blood stem cell donation, we think about the effects as short-term, which is within days to one week, or longer-term, which is beyond that. So in the shorter term for peripheral blood stem cell donation,
The adverse effects are actually associated with the use of GCSF, as I spoke about earlier, and these pertain to bone pain, fatigue, and a minority of our patients, like 0.6%, could potentially experience adverse or severe adverse side effects, such as splenic rupture, but that is very rare. And so when we think about long-term adverse effects,
GCSF is not associated with any increased risks of symptoms. And for bone marrow harvest, are there adverse events or effects that result from that? Yeah, so for bone marrow harvest, donors may experience bone pain, which is from where the procurement happens, and sometimes donors will also experience myalgias and fatigue.
And your article also mentions that although donors may experience happiness or satisfaction from being able to donate stem cells, some actually may have some anxiety after donation. Can you talk a little more about that? Yeah, so we've seen that sometimes on the one hand, donors have a lot of satisfaction from being able to help either a family member or an individual that they may not know who needs a stem cell transplant.
donors may experience anxiety. And we see that commonly for donors who are related donors. And this is in the context of them feeling pressured to donate because of their HLA compatibility with the recipient. And so sometimes psychological distress may also be associated with physical symptoms like bone pain and uncertainty about the stem cell transplant recipients. Because very often,
a donor may not know or have any contacts with the recipient. And so just concern and hoping that the stem cells work for the recipient can sometimes be a source of anxiety and uncertainty for our donors.
And your article also discusses disparities in donor access and challenges for ethnic minorities in the stem cell transplant donation process. Can you describe the probability of finding an unrelated stem cell donor based on race and ethnicity in the U.S.? And what are some potential reasons for the disparities?
Yeah, absolutely. You know, unfortunately, despite a lot of the advances that we have for this really powerful treatment, we see a lot of racial and ethnic disparities. And if you are a person who identifies as white, you have a 79% chance of finding a donor who is unrelated. And that drops to 60% for Native American patients.
And then it further drops to 48% for Hispanic patients. And then for patients who identify as Asian or Pacific Islanders, there is a further drop to 47%. The dramatic drop comes for patients who identify as Black, where they only have a 29% chance of finding an unrelated donor. And there are a few reasons why this is the case.
First, there are substantial differences in the HLA type diversity among certain racial and ethnic groups, such as our Black patients, that make it more difficult to find a donor in these populations. Another reason is also that there are smaller population sizes of racial and ethnic minority patients.
And then lastly, when a volunteer donor is identified, racial and ethnic differences in the donor availability and less willingness to proceed with a donation is observed among certain patients from racial or ethnic minority backgrounds compared to others, which further contributes to the disparities that we see in these groups. Can you describe some recent pharmacologic advances that have expanded the stem cell donor pool?
Yeah, so it's really been encouraging over the past few years that a few pharmacological advances gave us some hope and optimism about reducing some of these disparities. And one of them is the use of post-transplant cyclophosphamide and abatacept for GVHD prophylaxis.
And as we have used these medications, they've expanded the stem cell donor pool to include haploidentical and mismatch unrelated donor transplants. Where can people who are interested in becoming stem cell donors get more information about this process? So there are a few organizations that dedicate a lot of time and resources to stem cell donation in general.
In the U.S., the main organization is the NMDP. They organize a variety of community efforts through donor drives and campaigns to recruit stem cell donors. And they also devote a lot of time to expanding the diversity of our donor registries among minority populations, including our Black and Hispanic populations, to improve access.
In the world, the World Maru Donor Association, or the WMDA, also has different efforts in different places around the world outside the U.S. that also dedicates a lot of resources to ensuring that there is diversity in donor registries and also coordinates efforts such as donor drives to increase the number of people who donate stem cells.
Before closing, is there anything else that you'd like to mention that we haven't previously discussed? I think what I'll say is stem cell transplantation offers hope to a lot of our patients because it's one of the few therapeutics that we have for patients with cancer and otherwise that actually provides a potential for cure.
And stem cell donation, although it is somewhat mysterious to a lot of individuals, our hope is that this article would provide a bit more details to patients and clinicians about how to potentially contribute to this process as stem cell donors. And because of its power in helping patients who otherwise would have no other option for their illnesses.
Thank you so much for sharing your thoughts with us about this interesting and important topic. I'm Dr. Kristen Walter, and I've been speaking with Dr. Hermie Amanu about allogeneic stem cell donation. You can find a link to the article in this episode's description. To follow this and other JAMA Network podcasts, please visit us online at jamanetworkaudio.com or search for JAMA Network wherever you get your podcasts. Thanks for listening.
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