DR STONE: So APL, thanks to work done in Houston and in Rome, has undergone a revolution. Right now we can cure 95% of people with APL, certainly, maybe all APLs, but certainly those who present with nonhigh-risk disease — that is to say, a white count less than 10,000.

And so to start out the case, any patient with a white count less than 10,000 under age 70, which was according to the Lo-Coco paper that was published a couple of years ago in New England Journal of Medicine, which showed that ATRA and arsenic therapy alone, no chemo, was better than a chemo-based approach. So let me tell you how I tried to apply that to this patient.

Sixty-three-year-old guy with a history of aortic valve replacement presented last month with gum bleeding, low fibrinogen and pancytopenia. APL suspected. APL ATRA started immediately.

DR LOVE: Just before you go on, where was the diagnosis made? And who started the ATRA?

DR STONE: He came to me. He lived in a suburb of Boston. He came to me almost immediately after he had pancytopenia noted. And so we started it the night he showed up in the emergency room. The fellow called me, and I said, “Start ATRA” based on — the fellow also emailed me the smear. It looked like APL. He had a low fibrinogen. It was a classic case, so it wasn’t actually rocket science.

So we put him on ATRA. And he had early differentiation syndrome. And he was sick as heck. He ended up in the ICU with pulmonary infiltrates. He was intubated briefly. But we started prednisone as per the Lo-Coco recommendations, despite that he still had the infiltrates. His coagulopathy did get better from a laboratory standpoint, but he was getting sicker.

And we still managed to start the arsenic trioxide on day 2 or 3. But after about 2 doses of the arsenic trioxide, we noticed that his QTC interval was 570, so we had to stop that. And then after about 5 or 6 days of ATRA, his lipase climbed and he had belly pain, so we had to stop that. I’ve never seen it, but it’s a rare complication of retinoic acid. So what should we do with a patient who can’t get arsenic now, can’t get ATRA, or not safely, at least, in 2016?

DR CORTES: Is he African-American?

DR STONE: Nope. Why’d you ask?

DR CORTES: Because since we started doing this thing with the arsenic and ATRA, we saw that the African-Americans had more cardiac issues with the arsenic than the Hispanics, which are a common population for APL, or the Caucasians. So not exclusively, but they had more cardiac issues.

It’s hard, definitely. We try to do everything we can. And in a prior patient, we talked about involving cardiologists. And we involve them very closely to try to see if we can correct that QTC by either eliminating other drugs, pushing their potassium and their magnesium to the upper limits — not just to the normal but to the upper limits. Some of these things sometimes help. When you can’t, you can’t.

And we have a clinical trial. And our trial does include the addition of gemtuzumab ozogamicin, which is a drug that has activity in APL. But today, it’s not available. So that’s just a clinical trial. So I think if you at some point get to the situation where you definitely cannot use arsenic, and this early, certainly, I think you have to go back to the standard kind of regimen and continue that way.

Fortunately, he is tolerating the ATRA, because, at least —

DR STONE: No, he didn’t tolerate the ATRA. He had pancreatitis.

DR CORTES: That you can probably resume, I think.

DR STONE: Eventually.

DR CORTES: When it resolves.

DR LOVE: You start it again?

DR CORTES: Yes.

DR STONE: Having seen people die from L-asparaginase-induced rechallenge, I was a little nudgy about doing that right away. So I gave him idarubicin, according to the AIDA regimen, every other day for 4 doses. And he’s got mouth sores and the usual complications, but he seems to be getting through that. I will add back low-dose ATRA when I can and, hopefully, eventually arsenic. But this is obviously a one-off type of patient, very unusual.

DR COLE: Do you think that the differentiation syndrome may have triggered the pancreatitis?

DR STONE: Yes. I do. So that’s why I’m more willing to add back — I mean, it all happened at the same time. I mean, there was the sick patient, it’s hard to know what was going on when he was really sick in the ICU.

DR CORTES: One thing that I will mention, and I don't know if it’s your observation. And this is just an observation and it is not validated at all. But one thing that we have noticed is that — we’ve switched to a generic ATRA formulation. And we’re starting to see a lot more pancreatitis than we did in the past. It’s ATRA, but we didn’t used to see as much pancreatitis as we are seeing now.

DR STONE: That’s really interesting. I’ll have to check and see what he got.

Module 1: Current and future approaches to targeted therapy for acute myeloid leukemia (AML)

Module 2: Other clinical issues in AML management

Module 3: Case discussions