Treatment Options and Care for Patients Who Develop Therapy-Related AML - Episode 3

Diagnostic and Additional Testing for Diagnosis of t-AML

Rami Komrokji, MD:This patient is presenting with leukocytosis after 3 years. There is a differential diagnosis for leukocytosis. The differential diagnosis can vary from something that’s very simple, like an infection process, to acute myeloid leukemia. First, one would obtain a good history and physical exam and would see what setting the leukocytosis has happened in. When the blood counts are ordered, one should look at the differential of the white blood cells. Ideally, one should get a manual differential and a blood smear to review, because the type of leukocytosis is what dictates further workup.

Is it neutrophilia? That would indicate infection or a chronic process. Any increases in myeloblasts would make the diagnosis of AML and so forth. In that setting, if it’s neutrophilia, one would look for infections. One could look into myeloproliferative diseases if it’s persistent. If it’s the blasts that are increased, that would obviously lead to a diagnosis of acute myeloid leukemia. To make the diagnosis, the next step would be obtaining a bone marrow aspirate and biopsy. Nowadays, the bone marrow aspirate and biopsy are complemented by flow cytometry testing, where we can identify myeloblasts more accurately. However, morphology remains to be the main part in determining the percentage of the blasts. Cytogenetics is a must in testing when we do the bone marrow aspirate and biopsy, because the risk stratification for patients with acute myeloid leukemias is based on the cytogenetics.

And nowadays, we even go further to look at the level of the somatic gene mutations by next-generation sequencing. There are certain mutations that are incorporated into the risk stratification for patients, and there are available therapies for those. Testing forFLT3,NPM1, CEBPA—which is a favorable mutation—IDH1, andIDH2mutations is becoming routine for those patients. First, it has value in risk stratification. Second, there are targeted therapies available for treatment. The treatment could be tailored based on those mutations. In many cases, when we see those patients referred to us from the community, they are not tested.

We obviously focus on the disease and what tests we need to get for the disease, which include the things that we discussed, but I think we also have to look at the patient, the performance status for the patient, and comorbidities. That will determine some of our choices for treatment.

Typically, when thinking of intensive chemotherapy, we have to obtain baseline of cardiac function. Kidney functions are important. If the leukemia is proliferative, with hydration and medications for hyperuricemia, we can sometimes improve kidney function. High creatinine can dictate the treatment but can also predict the morbidity and mortality with treatment. Patients who have renal failure would do worse with intensive chemotherapy, in general. We also look at liver function and make sure that the patient doesn’t have transaminitis that would require adjusting medications or the prophylactic medications for infection.

Transcript edited for clarity.

Case: A 67-Year-Old Man with Therapy-Related AML

  • A 67-year-old man who had received CHOP for diffuse large B-cell lymphoma 3 years prior
  • PMH: hypertension controlled with amlodipine
  • Laboratory results:
    • WBC 15 x 109/L
    • Serum creatinine 1.5 mg/dL
    • Normal LFTs
    • LVEF 50%
  • Diagnosis: Acute Myeloid Leukemia
  • ECOG PS 1
  • The patient received liposomal cytarabine and daunorubicin
  • His course was complicated by febrile neutropenia
  • After induction, <5% marrow blasts, neutrophil count (>1400/&micro;L), platelets 60,000/&micro;L