Patient Profile 1: Patient with Secondary Acute Myeloid Leukemia

Eunice Wang, MD: This is Patient Profile 1. This is a 62-year-old woman who has a history of a prior malignancy, a triple-negative breast cancer for which she received neoadjuvant chemotherapy, including several cycles of anthracycline-based drugs, breast-conserving surgery, and then follow-up radiation therapy followed by adjuvant capecitabine and potential hormonal therapy. She has a long history of being treated for this solid tumor malignancy. Other than that, she’s relatively well. She has some hyperlipidemia, which is well controlled.

Despite taking some time off for her medical treatment, she continues to work full time as a teacher and remains active. About 4 years after completion of her adjuvant chemotherapy, she unfortunately presents with some persistent nosebleeds to her primary care doctor. He performs laboratory work, showing significant abnormalities. Her white blood cell count is now elevated at 24,000 per mm3, with evidence of abnormal cells constituting 20% of the peripheral blood. She has a hemoglobin of 7.1 g/dL and a platelet count that’s decreased to 43,000 per mm3. Creatinine is off slightly, at 1.5 mg/dL. Otherwise, her liver function tests are normal, and a recent echocardiogram as part of our cardiac work-ups showed a normal ejection faction. In your office, she looks great. She’s a little fatigued, but otherwise, her ECOG performance status is 1.

On examination, she has some evidence of recent nosebleeds, scattered bruises, and petechiae due to low platelets, but she’s otherwise well with a normal cardiopulmonary examination. However, a bone marrow biopsy confirms a diagnosis of a therapy-related or secondary AML [acute myeloid leukemia] with 40% myeloblasts. Her cytogenetics are normal with evidence on a rapid mutational profile of only a TET2 mutation, with no FLT3, IDH1, or IDH2.

Richard Stone, MD: Should we back up for a second? Do you agree that this patient has secondary AML? If so, why?

Eunice Wang, MD: The diagnosis of a secondary therapy-related AML is mostly because of the clinical history. As you mentioned, we have evidence of specific mutations that are tied to the biology of the underlying disease. But in this case, even without the mutational profile, she has developed an acute myeloid leukemia in the setting of prior myelotoxic chemotherapy, giving her a clinical diagnosis of therapy-related AML. Do you disagree with that? What are your thoughts? Do people need to keep doing that mutational profile to confirm that, or can they just do it based on history?

Richard Stone, MD: With history, she definitely has secondary AML. But this brings up 1 of the issues I mentioned in my starting remarks: we don’t know her cytogenetics. It could be normal. Her mutational profile is pretty benign. A TET2 mutation doesn’t put her into the Dr Coleman Lindsley secondary category. TET2 is epigenetic but not a chromatin-remodifying enzyme. This patient might have a better prognosis than we think. Obviously, cytogenetics could be bad. It’s at the right time frame to get what I call the worst flavor of secondary AML.

There are 2 types of secondary AML. There’s the alkylating agent type, which this patient may have. Then there’s epipodophyllotoxin type, which occurs with a shorter incubation period and tends to have an MLL [mixed-lineage leukemia] rearrangement, which in general fares a little better than the alkylating agent type that was first described after MOPP [mechlorethamine, vincristine, procarbazine, prednisone] chemotherapy. This patient definitely has secondary AML by history, but may have a better prognosis than the average patient with secondary AML. We aren’t told the cytogenetics, but the TET2 isn’t that bad. We don’t know the VAF [variant allele frequency] for the TET2 mutation. If it’s a low VAF, it could even be a CHIP mutation. This patient may have a pretty good prognosis.

Transcript edited for clarity.