Acute Myeloid Leukemia with Myelodysplastic-Related Cytogenetics - Episode 1

Case-Based Overview: De Novo Acute Myeloid Leukemia

July 23, 2019

James K. McCloskey II, MD:Our patient is a 68-year-old gentleman who comes in to us with shortness of breath and fatigue. He says he’s been having a low-grade fever for the last few days. His past medical history is otherwise pretty unremarkable—some hypertension and hyperlipidemia, both of which are pretty well managed medically and he’s never had any pre-existing history of malignancy. When he sees his PCP [primary care physician] they do some bloodwork, and we see that he’s mildly pancytopenic. His white blood cell count is 2.6 with an ANC [absolute neutrophil count] of 1.2. His platelets are 95, and his hemoglobin is mildly low at 9.4.

When a gentleman like this walks into the clinic, we’re always concerned about some kind of bone marrow disorder—MDS [myelodysplastic syndrome] or AML [acute myeloid leukemia] would certainly be on our radar. He’s most likely referred to a hematologist who performs a bone marrow biopsy. Sure enough, the bone marrow biopsy confirms AML with 65% blasts.

Additional testing returns and shows that the patient has a 20q deletion, as well as a deletion 5q. The combination of these cytogenetic abnormalities and the bone marrow blasts would be consistent with AML-MRC, or AML with myelodysplasia-related changes.

When we’re evaluating a patient with AML, a bone marrow biopsy is obviously crucial for confirming the diagnosis and accurately measuring the bone marrow involvement. We also will send samples for next-generation sequencing or molecular testing, and FISH [fluorescence in situ hybridization] for chromosomal abnormalities as well as your typical karyotype. All of these factors are really important to allow us to accurately risk stratify patients. The combination of molecular findings and cytogenetic abnormalities allow us to risk stratify patients into 1 of 3 groups.

These groups are patients with either favorable-risk disease, intermediate-risk disease, or high-risk disease. Certainly our patient who we’re discussing here, a patient over the age of 65 with a deletion 5q, would be a high-risk patient. Unfortunately for many of these patients over the age of 65 with high-risk molecular cytogenetic abnormalities, their 5-year survival is less than 5%.

For this patient who underwent a bone marrow biopsy, I would absolutely send additional testing. We do have results that tell us some type of karyotypic abnormalities, so we know he has a 5q minus. We know he has a deletion 20q. Whether that came on FISH or cytogenetics, we can’t be sure. But in addition to this, we would certainly want molecular testing, and that could be done in a variety of ways. We can send next-generation sequencing for a panel of a variety of mutations, or these could be tested individually using PCR [polymerase chain reaction] analysis. These results are more and more important every day in AML. At our institution, we will wait for those to return before we make a final decision for our patient in terms of treatment, because they often will affect treatment options for patients at the start of therapy.

The discussion of the definition of AML with myelodysplastic-related changes has been one that’s been a lot more active recently. This is a complicated diagnosis and really refers to a group of patients we often used to call secondary AML. AML-MRC is defined as more than 20% blasts in the bone marrow, and 1 of 3 different findings. Either the patient has an MDS-defining cytogenetic abnormality, these are commonly involving chromosomes 5 or 7, and so that one’s fairly easy. Or the patient has a prior history of MDS or CMML [chronic myelomonocytic leukemia], or an antecedent hematologic malignancy. But lastly, this includes patients with multilineage dysplasia. Multilineage dysplasia is the bone marrow specimen that our pathologist would look at and tell us that, “Gee, the background of this specimen contains a lot of dysplastic cells.” At least 50% of the cells involved are dysplastic involving at least 2 cell lines. Importantly, it would exclude patients withNPM1mutations or biallelicCEBPAmutations.

This really speaks to the difficulty that we have in making treatment decisions quickly, because we really are forced to wait for a lot of these results to come back so that we have the full picture before deciding on treatment. Depending on the institution, that could take up to 2 weeks. But AML physicians all over the country are really saying now that we are sitting on our hands for a while to allow these results to come back so that we can get an accurate interpretation. This is because it really takes an assessment of the bone marrow from our pathologist to tell us how many blasts are there, what does the background stromal environment look like, and time for the molecular and cytogenetic tests to return as well.

Transcript edited for clarity.


Case: A 68-Year-Old Man Withde novoAML

History and Physical:

  • A 68-year-old man presented with significant fatigue and shortness of breath on exertion; reports low-grade fever for the past few days.
  • PMH: mild hypertension, hypercholesterolemia, both medically managed; no history of malignancy

Laboratory work-up:

  • WBC, 2.6 X 109/L
  • ANC, 1.2 X 109/L
  • Hb, 9.4 X 109/L
  • Hct, 32%
  • RBC, 3.3 X 109/L
  • MCV, 121 fL
  • PLT, 95 X 109/L

Bone marrow biopsy:65% blasts

Peripheral blood smear;70% blasts

FISH;del(5q), del (20q)

Diagnosis;AML, myelodysplasia-related cytogenetic abnormalities