Episode 289 - Treating Leukemias: Past and Present With Hagop Kantarjian

So let's just start by how, when you first started, how, how were things? How was your thinking process? How was research at the time? And then how did things evolve?

Right.

So just as, [clears throat] um, as a background, when we think of leukemias, we divide them in our mind into the acute and chronic leukemia, and that's based on the course of the diseases if untreated.

So acute leukemias, patients live two years untreat, uh, two, two...

Patients lived about 22 months if untreated.

The chronic leukemias, they lived about, uh, couple of years.

And then we divide them by the cell of origin, so in simple ways, myeloid versus lymphoid.

So you have four main kinds of leukemia: acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, and chronic lymphocytic leukemia.

And then you have subsets like APL and core binding factor, acute myeloid leukemia as part of AML, and hairy cell leukemia, which is a cousin of chronic lymphocytic leukemia.

But I w- I like to divide them based on how the research has advanced from 1981 till now.

So if you think about them, in 1981, most of the leukemias were in what is called unfavorable category, meaning their five-year survival was less than 30%.

There was one intermediate leukemia, acute promyelocytic leukemia, and that's because, uh, anthracyclines were discovered in the '70s.

So with anthracyclines, acute promyelocytic leukemia had a five-year survival of about 40%, and then there were no favorable leukemias.

There were no leukemias where you could say that the five or 10-year survival is, uh, above, uh, 70%.

So when I started in 1981, the two acute leukemias, AML and ALL, were curable at the rate of 20% with intensive chemotherapy.

Uh, these are the adult ALL.

In the chronic leukemia, both CML and CLL were incurable, and the five-year survival was about also, um, uh, 10 to 20%.

You fast-forward to today, most of the leukemias have shifted to the favorable category, meaning we expect their survival to be over 70% or 80% at five to 10 years.

Then we have an intermediate group of leukemia, where also there are substantial subsets.

And now we, uh, have seen that among the unfavorable leukemia, there's only two simple categories, the older patients with AML and patients with maybe TP53 and MYCN.

So if you like, I could take you through the progress in each of these entities and, uh, uh-

Sure, yeah

... going from the most favorable to the least favorable, but also to show that there's no one path for curing cancer.

Uh, a lot of it is trial and error, and also much of it is deciphering the pathophysiology of particular leukemias and then developing drugs that target those pathophysiologies.

I would love to do that.

So let's just start by how, when you first started, how, how were things? How was your thinking process? How was research at the time? And then how did things evolve?

Right.

So just as, [clears throat] um, as a background, when we think of leukemias, we divide them in our mind into the acute and chronic leukemia, and that's based on the course of the diseases if untreated.

So acute leukemias, patients live two years untreat, uh, two, two...

Patients lived about 22 months if untreated.

The chronic leukemias, they lived about, uh, couple of years.

And then we divide them by the cell of origin, so in simple ways, myeloid versus lymphoid.

So you have four main kinds of leukemia: acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, and chronic lymphocytic leukemia.

And then you have subsets like APL and core binding factor, acute myeloid leukemia as part of AML, and hairy cell leukemia, which is a cousin of chronic lymphocytic leukemia.

But I w- I like to divide them based on how the research has advanced from 1981 till now.

So if you think about them, in 1981, most of the leukemias were in what is called unfavorable category, meaning their five-year survival was less than 30%.

There was one intermediate leukemia, acute promyelocytic leukemia, and that's because, uh, anthracyclines were discovered in the '70s.

So with anthracyclines, acute promyelocytic leukemia had a five-year survival of about 40%, and then there were no favorable leukemias.

There were no leukemias where you could say that the five or 10-year survival is, uh, above, uh, 70%.

So when I started in 1981, the two acute leukemias, AML and ALL, were curable at the rate of 20% with intensive chemotherapy.

Uh, these are the adult ALL.

In the chronic leukemia, both CML and CLL were incurable, and the five-year survival was about also, um, uh, 10 to 20%.

You fast-forward to today, most of the leukemias have shifted to the favorable category, meaning we expect their survival to be over 70% or 80% at five to 10 years.

Then we have an intermediate group of leukemia, where also there are substantial subsets.

And now we, uh, have seen that among the unfavorable leukemia, there's only two simple categories, the older patients with AML and patients with maybe TP53 and MYCN.

So if you like, I could take you through the progress in each of these entities and, uh, uh-

Sure, yeah

... going from the most favorable to the least favorable, but also to show that there's no one path for curing cancer.

Uh, a lot of it is trial and error, and also much of it is deciphering the pathophysiology of particular leukemias and then developing drugs that target those pathophysiologies.

I would love to do that.