What is an autologous stem cell transplant (ASCT)?

What is an autologous stem cell transplant (ASCT)?

So an autologous stem cell transplant, we call it by several different names. One of the names is a peripheral blood stem cell transplant. And the name is a high dose chemotherapy with stem cell support. I like the term high dose chemotherapy with stem cell support, because that's what we actually do.

It's a process in which we use a very high dose of chemotherapy that we normally cannot give to a person. We use that to kill their bone marrow entirely, which basically destroys the myeloma and the person's bone marrow and also their normal cells to the bone marrow.

So that if we gave it to a person without further stem cell support, that bone marrow would never function and that would be fatal. So what we actually do is collect stem cells, which are mother cells or seed cells of the bone marrow from the person, store them away in a freezer, and then give them the high dose of chemotherapy, which essentially achieves what we call myeloablation, which means destroys the bone marrow completely.

So both the myeloma cells and the normal cells get destroyed, and then we use the stored frozen stem cells out we use, tore them all and infuse them back into the patient through their veins. The cells know how to go back to the bone marrow. They go there and over the course of the next two weeks, they recover and the bone marrow works normally.

Now, hopefully rid of the myeloma cells. Stem cell transplant is a procedure whereby we collect blood or marrow stem cells from a patient. Put those in the freezer temporarily. And have the patient come in to receive high dose chemotherapy using a drug called Mephalan. And then once the Melphalan is cleared from the bloodstream, we give the stem cells back to build up the blood counts.

This way, a patients can receive high dose chemotherapy, which hopefully will knock down or knock out their myeloma while allowing us to rescue their bone marrow. Their blood counts from the effects of the high dose chemotherapy using the previously collected blood or marrow.

So this has been a time honored treatment for multiple myeloma. In fact, for all the treatments that we have that have changed the course of history in myeloma patients, this is one of the most important started coming in the late 1980s and it became very well established in the next two decades.

Why is ASCT effective?

Basically stem cell transplants work. When you have a treatment that when applied in a very high dose kills myeloma cells proportionately more. So we have a drug called Melphalan which is again, it was probably the first ever chemotherapy that works for myeloma well.

That people found that there is a dose response effect for Melphalan that you give a higher dose, more cells get killed. So we got up to when we get up to the higher doses, we find that Melphalan destroys the normal cells in the bone marrow too much and in the bone marrow doesn't recover back to have normal function.

So it works in myeloma, basically because we have a drug that is very effective at killing myeloma in a very high at a high dose. And for that purpose, we need this we need normal stem cells to rescue the person from that high dose of chemotherapy after we have given such chemotherapy.

The cells that we give to the patient generally are not thought to do much, although in some cases you could argue that they do have. They do restore immune function and there is a little bit of an immune reboot that happens. But the vast majority of the effect in an autologous stem cell transplant or an auto transplant, which is the main transplant for myeloma, happens from the high dose of chemotherapy that we use.

Is autologous stem cell transplant (ASCT) safe?

So high dose Mephalan and autologous stem cell transplantation is very safe. The likelihood of life threatening complications is very low. Most centers would code, value of 1% or less. Having side effects, I think probably, at least a third of the patients will have, grade three or four toxicities.

These are non hematologic toxicities. Almost every patient will develop an cytokine during the process. But the tolerability of high dose Mephalan has improved primarily because the supportive care that we provide to patients has improved over the last 25, 30 years.

So the reason why it's advantages is because of the data generated from back in the eighties and nineties showing that when you can we compared high dose Melphalan to conventional chemotherapy you have better survival outcomes for myeloma patients.

But each time one of those studies would come out the discussion would be well the standard of care for myeloma is changing. So what does this high dose Melphalan really help us in the context of novel agents that we are giving to patients as part of induction treatment, as part of maintenance treatment.

Is it really the Melphalan that's creating the value for the patient in terms of survival outcomes here or not. To date, what we know with novel agent induction and maintenance treatments that at the very least the depth of response and PFS is better when you give high dose Melphalan to myeloma patients in the frontline setting.

Will high dose Melphalan be replaced by other cellular therapy modalities in the future?

Sure. I think that that can certainly happen. The goal of treatment is to get better depth of response get patients to both flow imaging or sequencing and imaging and MRD negativity, because that portends the best PFS at the very least.

so with that depth of response being the goal, it doesn't matter how you get there, you want to get there with efficacious regimens and without causing a lot of toxicities.

So even though, I'm saying that high dose Melphalan should be part of that frontline approach for patients, if we get better drugs that are safer and do the same job, why the heck not? We'll go ahead and change our treatment paradigm.