DR JOHL: So it’s a 58-year-old Caucasian gentleman I saw earlier this year, presented with pancytopenia. White count was 1.7 and platelets are 10. Low fibrinogen and classic morphological features, promyelocytes seen on the marrow and peripheral blood. FISH and cytogenetics confirmed the diagnosis, so we started him on the same regimen that you mentioned, ATRA and arsenic. And then even though he did not have differentiation syndrome, he started retaining fluid — a lot of lower extremity edema, pleural effusion, et cetera.

So we pushed him through induction, diuresed him. He was in the hospital almost 45 days. And marrow at recovery did show he was in complete hematological cytogenetic and actually even molecular remission. So we went on to consolidation just like the Lo-Coco paper, with arsenic and ATRA, but the same thing happened: lower extremity edema, worsening pleural effusion. He actually had pericardial effusion to the point where he tamponaded, ended up in the hospital and needed a pericardial window.

And at that point, we were thinking, “It didn’t look like differentiation syndrome from ATRA. It looked like a toxicity of arsenic.” And we looked it up, and sure enough, there’s papers on third spacing of fluids, pericardial effusions. So what I decided to do is stop his arsenic. And we had to stop his ATRA temporarily. He was in ICU, intubated, et cetera. So once he recovered, the question is, how do you manage a patient like this?

And what I decided to do is, because we were having continuing problems with arsenic, to stop the arsenic and go back to the older way of treating APL based on the CALGB 9710 protocol, with anthracycline plus ATRA. So we did 2 cycles of that. He did beautifully. He’s recovered after his second consolidation. But I just wanted to see if any of you had any complications of arsenic in this fashion or if you would have done anything differently than what I did.

DR STONE: I think that was expertly managed, actually. I’ve never seen that from arsenic. Clearly you can’t get differentiation syndrome if you’re in remission. So it’s not differentiation syndrome. And I would have guessed that might have been the ATRA problem. But you’re saying he’s tolerating the ATRA fine now?

DR JOHL: He’s tolerating ATRA just fine.

DR STONE: So it was the arsenic. So you can’t give him more arsenic. You don’t want him back in the ICU. So I would have done exactly what you did. I would have gone to the PETHEMA consolidation, which is several cycles of anthracycline plus retinoic acid, or the CALGB consolidation, the Powell paper, CALGB 9710, like you did. That’s perfectly fine.

The issue is whether he should get maintenance therapy with ATRA and antimetabolites. I probably would since he got shortchanged on the arsenic, but he’s probably going to do fine, especially if his postconsolidation marrow shows molecular negativity.

DR FEINSTEIN: What are your individual practices as they pertain to high-risk APL?

DR STONE: I use the CALGB 9710 Powell regimen for high-risk APL. It’s probably overkill. My heart of hearts believes that the Lo-Coco regimen would be fine in high-risk APL, but I can’t prove that. So I still go back to either the 9710 regimen, which is 4 + 7 plus ATRA, followed by 2 months of arsenic, followed by ATRA, daunorubicin. I usually skip the maintenance because I don’t think that helps. Or you can use the Australian Leukemia Study Group regimen, which is mainly anthracycline, less ara-C and arsenic. And that seems to work okay in high-risk patients too.

DR CORTES: Yes. What we do is, we use the anthracycline. So before we introduce the gemtuzumab, as what we were doing. Then gemtuzumab, we started going, then it was taken away. We switched back to idarubicin. And these patients are very sensitive to anthracyclines. This is one disease where the anthracycline seems to have a much bigger role than the ara-C. So that’s what we’ve done on these patients to give them idarubicin. Now we do it with ATRA and arsenic, so it’s not the AIDA. It’s the ATRA/arsenic plus idarubicin. But that’s what we do.

One thing I want to just throw in briefly, which is very important for the APLs, I think patients with APL frequently present with low counts, which is a good thing. One important thing to remember is that any patient where you have the slightest suspicion of an APL, you should not give them growth factors. We talked about the growth factors in AML, and this is a population where you do not want to give them growth factors, because they’re neutropenic while you’re waiting or whatever, definitely not.

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