Investigating Pregnancy and Transplant Match Issues

Multipotent stem cells in the bone marrow: © Juan Gärtner - stock.adobe.com

While certain patient demographics like minority racial and ethnic backgrounds have been established to have more difficulty identifying an HLA match for a transplant, there has been little research performed on how HLA antibody burden affects the ability to find an HLA match.

Notably, multiparous women who have carried multiple pregnancies were hypothesized to have higher levels of HLA antibody burden, making the HLA matching process more difficult.

A study performed by Warren Fingrut, MD, and colleagues looked at adult patients with blood cancers who received allograft transplants from partially or fully matched donors. The researchers found that a significant number of transplant patients had high HLA antibody levels, especially multiparous women. Additionally, patients with high HLA antibodies were less likely to receive haploidentical grafts.

These findings suggest that transplant centers should consider a patient's pregnancy history when assessing their suitability for different donor types. Further research is needed to understand the impact of these antibodies on transplant outcomes and to develop methods to reduce them before transplantation.

In an interview with Targeted Oncology^TM, Fingrut, a transplant physician and assistant professor at The University of Texas MD Anderson Cancer Center, discussed the study and its findings which were presented at the 2024 Transplantation and Cellular Therapy Tandem Meetings.

Targeted Oncology: What was the inspiration for this study?

Fingrut: With respect to the study that I conducted, examining gender disparities in HLA antibody burden, we know that HLA antibodies are important because they are a risk factor for poor outcomes, specifically failure to engraft posttransplant, and so much so that guidelines recommend against the selection of grafts for which there are donor-specific antibodies. However, the relationship between HLA antibody burden and patient demographic factors, specifically, sex and parity and donor selection, is not established. Additionally, there has not been a standard way to classify HLA antibody burden, whereas we know that patients either do or do not have HLA antibodies based on the screen that's performed. Additionally, we know that there are some patients that have many insulin antibodies and with high titers, there's no standard cut off or way to classify patient is having a high or low HLA antibody burden. With this study, we hypothesized that multiparous female patients have a high burden of HLA antibodies, and that impacts their choice of donor when it comes to allograft success.

What was being evaluated in this study?

In this study, we examined 672 allograft recipients at our center examining their HLA antibody burden by overall and by sex/parity and by donor type as well. I hypothesized that multipurpose women had a high HLA antibody burden, and that has impacted the choice of donor that was available for them with respect to their allograft access.

Could you summarize the findings?

We found that over 10% of patients were both broadly and highly sensitized against HLA, which is far more than maybe would have been expected. Again, considering that an analysis of this type had not been done before, but specifically, we showed that the multiparous female patients carried the majority of this HLA antibody burden. When we looked at the proportion of highly and broadly sensitized patients, we found that the majority of those patients were multiparous women, and again, multiparous women had the highest proportion with high and broad sensitization to HLA. We also showed that having a high burden of HLA antibodies was associated with choice of donor where haploidentical graft recipients in the study were the least likely to have either a positive HLA antibody screen or to be highly and broadly sensitized against HLA.

Now that a disparity has been determined, what are the next steps for evaluating this and overcoming it?

This study has multiple important implications.We know from the study that if [one is] evaluating a patient who is a multiparous female, it is important to consider upfront the challenge with respect to finding a haploidentical donor for them. This is increasingly relevant when you consider the intersectionality that such patients could have if they're also from a racial ethnic minority group. We know for example, that patients from underserved racial ethnic populations are less likely to have a fully matched unrelated donor available to them. If there are multiparous women that are less likely because of HLA antibody burden to have a haploidentical donor available to them. When you consider mismatched unrelated donor and cord blood, there are additional options that could be and should be pursued for these patients.

It is also important to recognize that there can be challenges accessing these grafts as well for the patients, where patients from underserved racial and ethnic minorities may be less likely to have an available, matched or mismatched, unrelated donor, and cord blood transplantation has been declining in our field and may not be an option at many transplant centers. These barriers stack for the multiparous female patients of non-European ancestry who are from racial ethnic minority, patients where if you go donor type by donor type, their population has challenges accessing grafts. It is important for us to consider that.

Now at the outset, the transplant center should be, at time of initial allograft evaluation, performing ancestry and parity histories for all their patients and be screening for HLA antibodies and should be using this information along with search prognosis score to triage patients early on to either need to be unrelated donor or to an alternative graft source, which should be pursued in earnest at the outset for these patients to ensure that patients can make it to transplant without delays. Futile unrelated donor searches should be abandoned as well.

The abstract also highlights the urgent need to develop approaches to desensitize patients against HLA antibodies. We know that that will be important for all patients, and that patients with a history of pregnancies will be uplifted more greatly than the total patient population should we develop new approaches to desensitize patients to HLA antibodies.

REFERENCE:

Fingrut, W, Davis E, Archer A, et al. Gender disparities in allograft access due to HLA-sensitization in multiparous women: implications for evaluation of female patients for alternative donor transplantation. Presented at: 2024 Transplantation and Cellular Therapies Tandem Meeting. February 21-24, 2024. San Antonio, TX. Abstract 28.