When is a stem cell transplant considered for ALL, and what factors determine that decision?

When is a stem cell transplant considered for ALL, and what factors determine that decision?

The approach to transplant in ALL is fairly nuanced. There used to be certain subtypes that, we would refer those patients to transplant very early on. Now we know that in patients who achieve really good response for most patients, we can defer transplant during their first remission. As long as they have a very good deep response.

The patients who definitely need to go to transplant are people who relapse. And of course, there are people who are not fit for transplant. And those patients, we don't offer transplant. But people who have relapsed disease, once we get them back into a remission transplant is usually the goal, with many caveats to that, but we generally reserve it for people who relapse.

And then there are still a few subtypes where most likely transplant in that first remission after we do the induction and often deepen the remission a bit with some consolidation, we try to get them to transplant. Some examples of that are people who have a mixed phenotype, acute leukemia. The overwhelming data suggests that those patients do benefit from a transplant soon after they get into remission.

There are people with, type of, genetic abnormalities that we detect on their initial bone marrow biopsy specimens, like hypodiploid ALL, some things some people might hear about. And those patients, many of them benefit from transplant. I think a lot of, people might be hearing about KMT 2A rearrangements ALL, this is increasing area of interest because we do have other targeted drugs that I didn't mention before that target, those particular leukemias and those patients have fairly high risk of relapse if we don't do a transplant. So we do usually refer those patients for transplant.

There are many other subtypes that we use transplant for. But I think it's still a very, very important modality. The question of whether people still need transplants after getting CAR-T cell therapy is a very open one, and we're still learning a lot about that.

Stem cell transplantation is known by a number of different names, including the older name bone marrow transplantation as well as the name hematopoietic cell transplantation. But broadly we'll just use the term stem cell transplantation here, which generally in ALL refers to someone receiving immune cells from a different donor with the goal of eradicating residual cancer cells.

Patients generally receive some degree of chemotherapy prior to their transplant, both to help eradicate residual disease, as well as to create a platform for host donor tolerance so that the immune system, of the recipient of the stem cell transplant does not reject the cells from the new donor.

The factors that determine whether someone is appropriate for a stem cell transplant include a number of factors related to the leukemia, including the genetic makeup of the leukemia, as well as how well someone is responding to their treatment, meaning how quickly they're clearing their MRD, as well as a number of considerations just regarding the health of the patient and whether we think that the benefits of the transplant would outweigh the risks.

On the first issue, while we're getting better and better at treating acute lymphoblastic leukemia, and while many patients, can be cured without a stem cell transplant, there are still some higher risk subtypes of ALL, where we believe that the risk of relapse after standard treatment is high enough to justify doing a transplant in first remission.

It's important to talk with your hematologist and collagist after you've had initial profiling of your leukemia, by chromosome testing and by molecular testing, to determine whether that's something that would be appropriate for you.

For example, patients that have a specific type of Ph-like ALL or Philadelphia chromosome, like ALL with a CRF2 rearrangement are at high risk as our patients with a high risk fusion called TCF3-HLF, I could list a lot more. But most importantly, it's a good idea to talk with your hematologist oncologist about the features of your leukemia in terms of response by MRD testing, as I said, we do MRD testing using a number of different techniques, including flow cytometry and molecular methods at different points during treatment, generally after induction and after some component of consolidation therapy.

If someone is not clearing their minimal residual disease despite ongoing treatment, we'll think about a number of therapeutic options for them, including the bispecific engager blenatumumab for patients with B-cell ALL. However, ultimately in those patients, we are often looking at a stem cell transplant as a definitive way to address that person's leukemia.

Broadly, if that person's leukemia is not clearing briskly and fully with treatments like chemotherapy and targeted therapy, we're concerned that in the long run, even if we're able to get that person into a basic level of remission, that they're at higher risk of relapse down the line.

Finally, when it comes to evaluating a particular candidate, we have to assess what someone's cardiac function is like, what their lung function is like, what their daily their performance status is like, for example, how well they're able to complete their activities of daily living, what other side effects they might have had from their treatment, and other factors that could influence their risk of getting chemotherapy, followed by the cells from a new immune system, basically, and using all of that information, we're able to talk with our stem cell transplant colleagues regarding whether we feel like the risks, or benefits outweigh one another, in terms of proceeding to a stem cell transplant or benefits outweigh one another, in terms of proceeding to a stem cell transplant.