Examining Allogeneic Stem Cell Transplant in Patients Without an HLA Matched Donor

In an interview with Targeted Oncology, Anne Wooford, MD, discussed a study of 27 patients with a variety of hematological conditions, unable to find a human leukocyte match donor.

While allogeneic stem cell transplant (ASCT) is currently the only curative modality available for some hematologic malignancies and bone marrow failure diseases.

However, due to ethnic disparities in specific populations, especially for ethnic minorities, the ability to get a human leukocyte antigen (HLA) match related or unrelated donor is not always available.

A study conducted by experts at Wake Forest Baptist Health, including Anne Wooford, MD, enrolled a total of 27 patients with a variety of hematological conditions who were unable to find an HLA match donor. Patients were treated on an IRB-approved protocol using haploidentcal donors in ASCT.

All of those enrolled in the study went through conditioning and received fludarabine total body irradiation. Most individuals received a reduced intensity conditioning, and 2 received a myeloablative prior to transplant.

Overall, they found that the rates of complication and survival were comparable between these patients and those able to receive more traditional, either match related or matched, unrelated donor graphs.

In an interview with Targeted OncologyTM, Wooford explained that results for patients who received traditional, match related or matched, unrelated donor graphs were comparable. She hopes that these data will allow for a larger variety of patients to obtain transplants.

TARGETED ONCOLOGY: Can you describe the your recent research on ASCT?

Wooford: This was a clinical study that we did at Wake Forest looking at the patient experience and outcomes for haploidentical stem cell transplant. This involved 27 patients who were unable to find an HLA match donor, and they had a variety of hematological conditions for which this was standard of therapy for a potential cure. All of these patients had a haploidentical donor available to them. What that is when you're looking for a donor for a stem cell transplant, you want to have the human leukocyte antigens matched or the HLA matched.

Some patients are not able to find a match donor. This disproportionately affects ethnic minorities who may be underrepresented in the National Marrow Donor Registry program. An alternate donor source is a haplo donor. Instead of having an exact match for all of your human leukocyte antigens, you're a half match, so you have a complete match on 1 allele that you received from a parent or that you gave to your child.

How was this topic previously investigated?

This was investigated as a transplant source earlier in time, and unfortunately at that time, it was not able to be utilized due to overwhelming complications, such as graft versus host until you're doing graft. Our hope is that we will be able to utilize this as a standard transplant source in the future by improving the preoperative regimen, and through improved supportive care after the transplant.

Can you explain the methods and findings of the study?

What we looked at Wake [Forest Baptist Health] were 27 individuals who were unable to basically have a stem cell transplant, they did not have a matched HLA donor through the registry or through their family, but they did have haploid donors. All of them went through conditioning and all of the patients received fludarabine total body irradiation, most of them received a reduced intensity conditioning, [and] I think there were 2 that received a myeloablative and then had their transplant.

What makes this unique is that 1 of the early complications of haplo-transplants is that they can have hyper acute GVHD. That's caused by a population of T cells that come up very early after the stem cell transplant, so less than a week after the transplant. This has been overcome by getting post-transplant cytoxan, and all of these patients went through that. We monitored them in the hospital to see how quickly their cells engrafted in them to see what kind of complications they had.

What we found was that overall, the sort of rates of complication and survival were comparable to patients that can receive more traditional, either match related or matched, unrelated donor graphs. I think in general, we were expecting that and certainly hoping for that, because this does open transplant to a wider variety of patients that might otherwise be able to receive it.

How have other studies explored this topic?

Previous studies have looked at similar outcomes. We don't want to give people this kind of transplant if we're not able to support them through it. I think right now, the literature is just trying to refine the conditioning process, which is the chemotherapy that's given prior to the stem cell transplant, and look at what areas can be improved with supportive care, GVHD prophylaxis, such as the post-transplant cytoxan.

What would you say are the next steps for this process?

Some of the next steps are letting our data mature. Due to the timing of transplant, we have some patients that will age into the day 101-year post transplant outcomes. What we did find for that was at 100 days, we had 80% disease-free survival, and 92% overall survival, which was fantastic. We were able to analyze 25 out of 27 patients at that point. In a year, we only had 21 patients out of 27, and unfortunately at that point, we only had 45% disease-free survival, and 70% overall survival.

We're hoping that when we look at the last 6 patients that will mature after this July, that we'll be able to just refine that data and look into it and look into what areas there are for improvement at our institution.

What unmet needs still have to be filled in the space?

In transplant in general, there is a very high maintenance [or] medical intervention, if you will. I think that in addition to improving outcomes in this space, we can look into improving outreach and improving the ability of patients that live in rural areas to be able to take advantage of transplant and how to best reach those patients and patients that may be underinsured.

How do community oncologists play a role in your research?

I am grateful that [community oncologists] are there to help us care for the patients that we care for as a tertiary medical center that has a large, for-all catchment area. We couldn't do what we do for our rural patients without them and I am incredibly grateful that they are there and that they continue to trust us to care for their patients with them.