What is Optimal Donor Type for Patients With Cancer in Need of SCT?

Salman Fazal, MD

While younger matched donors and older matched sibling donors provide similar outcomes, matched sibling donors are the optimal donor type for patients with cancer in need of a stem cell transplant, according to Salman Fazal, MD.

According to previous research, 3 to 5-year survival rates and outcomes between these donors are similar. However, a study published in Blood revealed that the average 3-year overall survival for patients with a matched sibling donor was 46% while it was 43% for unrelated donors. Having a matched sibling donor also lowered the risk of acute graft-versus-host-disease (GVHD).

“[A]t this point in time, even if we have a matched sibling, probably even above the age of 50, we would prefer using that matched sibling over a younger matched unrelated donor,” Fazal, director of the cell transplantation program in the division of hematology & cellular therapy at the Allegheny Health Network, told Targeted Oncology^TM.

In the interview, Fazal discussed the differences between older matched sibling donors vs younger unrelated donors in stem cell transplants and donor preferences at his institution for patients with cancer.

Targeted Oncology: What is the difference between younger, matched, unrelated donors and donor matched sibling donors? According to research, which achieves the better results?

Fazal: For each patient, we sometimes do not have the option of choosing between matched sibling [donor] vs an unrelated donor. So, if we have a match on an unrelated donor, we take that match from the unrelated donor for allogeneic stem cell transplant. However, in a situation where we have the options between an older matched sibling vs a younger matched unrelated donor the clinical study that was published in Blood, roughly about 8 to 10 years ago, looked at this comparison.

[They] found that using a matched sibling has resulted in a better outcome in terms of lowering the risk of acute and chronic graft versus host disease, and other complications related to transplant. So, at this point in time, even if we have a matched sibling, probably even above the age of 50, we would prefer using that matched sibling over a younger matched unrelated donor.

Can you discuss what kind of disease-free survival we're seeing with young matched unrelated donors?

It is very relevant in terms of disease-free survival. It depends upon the type of disease the patient has, whether we're dealing with acute leukemia or myelodysplastic syndrome, and we're also dependent upon their status of the disease moving into the transplantation. In general, for different types of acute leukemia, depending upon the intensity of the conditioning, the disease-free survival rates vary between 50% to 70%, depending upon the status of the disease and the intensity of the conditioning chemotherapy. We do try to improve the disease-free survival with maintenance therapies which are used in conjunction with reducing the immunosuppression following the stem cell transplant to improve the disease-free survival.

Can you talk about acute and chronic GVHD occurring and younger match unrelated donor transplant?

Over the last few years, there has been a lot of interest in terms of using different modalities to lower the risk of acute and chronic graft-versus-host disease. I always feel that we would be performing more allogeneic stem cell transplantation for different diseases if there was no significant risk of acute or chronic graft-versus-host disease. In general, the matched donors prefer per cell transplantation, there have been different modalities or methods have been used to lower the risk of acute and chronic graft-versus-host disease. Historically, we have used strategies, which include calcineurin inhibitors and methotrexate to lower the risk of graft-versus-host disease.

More recently, there was a study which compared tacrolimus and methotrexate with post-transplant cyclophosphamide to further lower the risk of graft-versus-host disease. We found that using post-transplant cyclophosphamide, even in matched related donors, led to lowering the risk of acute and chronic graft-versus-host disease. However, that study did not have the comparator arm with antithymocyte globulin, which is 1 of the other modalities that has been used to lower the risk of acute and chronic graft-versus-host disease. But as we all know, post-transplant cyclophosphamide came into the scene with the haploidentical transplantation, and now it is making its way in other types of transplantation, including measuring later donor transplantation. It has shown that it is an effective strategy in terms of both acute and chronic efforts. However, we do still see significant risk of both acute and chronic, although I believe that chronic graft-versus-host disease remains a challenge in terms of allogeneic stem cell transplantation.

What is the donor preference in your institution and what studies support that choice?

It all depends upon each individual patient, which options we have at our institution, and we do always consider matched siblings and over a matched unrelated donor. However, unfortunately, because of health conditions and other exceptions, matches are not sometimes available in those circumstances. We do prefer using a match on a later donor for transplantation. However, in situations where we do not have a match and later donor, then we are posed with the question whether we choose a mismatched, unrelated donor vs a haploidentical transplantation?

Currently, that trial is ongoing in terms of trying to figure out which is a better strategy in that type of situation. Is a mismatched unrelated donor transplantation a better option than a haploidentical transplantation? At this time, at our institution, because of the reliability of haploidentical transplantation and immediate availability of the donor, we do usually prefer to proceed with the haploidentical transplantation.

I think clinical trials have to show that if using a haploidentical transplantation is associated with better outcomes as compared with mismatched unrelated donors, I think the use of post-transplant cyclophosphamide in haploidentical transplantation has now made its way of using post-transplant cyclophosphamide following mismatched unrelated donor transplantation as well. I think in that context, the outcomes probably could be similar between the 2 strategies. However, because of the reliability of availability of the donor with the haploidentical transplant and with the unrelated donor, we always are concerned about the possibility of a situation where an unrelated donor is unavailable. In that situation, the patient may be left with delay in transplantation. We like to proceed with haploidentical transplantation because of its reliability of availability. I think that is also stems from the time when we were doing transplantation during the COVID pandemic because during the COVID pandemic, it was much more practical to use a haploidentical transplant donor where we don’t have to cryopreserve the cells and use the the or the fresh stem cells from the haploidentical donor.

Can you discuss haploidentical donors and their overall survival and relapse-free survival data?

In general, with haploidentical transplantation, there is overall improvement in the outcomes. However, we still prefer to do unrelated donor vs haploidentical transplantation. There are certain institutions across the country that do prefer haploidentical transplant over unrelated donors. However, now, at least at our institution, we prefer to do match unrelated donor transplantation. In terms of the outcomes of the haploidentical transplantation, it is dependent on different diseases. In terms of acute leukemia, depending upon the intensity of conditioning, chemotherapy, and the status of the disease, the outcomes vary. Again, in terms of acute leukemia, as I mentioned earlier, the disease-free survival rates vary between 50% to 70%. Outcomes with chronic graft-versus-host disease vary somewhere between 30% to 50%. Up to 50% can develop graft-versus-host disease, however, the majority of these graft-versus-host diseases are mild to moderate.

How would you advise other doctors on deciding on which donor to select in deciding when to do a transplant?

In terms of the other dissenters, I would prefer that we continue to use the match unrelated donor. However, I think, for mismatch vs the haploidentical transplant, we certainly have to look at the data. I do like the idea that the haploidentical has the bigger liability. So, I think in those situations, taking a haploidentical donor is preferable over a mismatched unrelated donor.

In terms of the difference for transplantation, we hope that the transplant physician is involved with the care of the patient from the beginning. There are situations in acute leukemia, where the choice of initial therapy impacts the post-transplant outcome. There are situations even with the availability of immunotherapy where use of certain agents can increase the risk of graft-versus-host disease and such complications after transplantation. I think incorporating the transplant physician in terms of choice of initial therapy, and then getting them to the transplant physician in a timely fashion is important.

Data that was presented in terms of comparing post-transplant cyclophosphamide vs tacrolimus and methotrexate confirmed that post-transplant cyclophosphamide does improve the outcomes following the transplantation. I think using these during this phase 2 clinical trials are a way to improve patient outcomes following the transplantation.