DISTINCT FEATURES OF
sAML SUBTYPES

((Dr. Jonathan Abbas))

Welcome, everyone. Today we are going to talk about some challenges in managing sAML subtypes, including t-AML and AML-MRC.

I’m Dr. Jonathan Abbas, the director of the acute leukemia and blood cancer program with Tennessee Oncology in Nashville, Tennessee. I’ve been treating patients with blood cancers, specifically acute leukemia, for over a decade, and my center does over a hundred inductions a year in patients with AML, many of them with therapy-related AML and AML-MRC.

t-AML and AML-MRC have high-risk features and account for approximately 30% of all AML cases. t-AML is classified by the WHO as AML that arises from treatment with cytotoxic chemotherapy or ionizing radiotherapy for an unrelated disease or prior cancer. Subtypes of t-AML include:

• t-AML following alkylating agents and/or radiation therapy, which is a classical subtype and has a resemblance to primary MDS
• t-AML following chemotherapy with topoisomerase II inhibitors is characterized by translocations such as 11q23 or 21q22
• t-AML following immunosuppressive therapies in patients treated for non-malignant conditions or treated with cytotoxic therapy for autoimmune disorders

AML-MRC makes up approximately 25% of all AML cases and includes patients with or without prior history of MDS or MDS/MPN.

The WHO classifies AML-MRC as ≥20% blasts in the peripheral blood or bone marrow and at least one of these criteria:

• Previously documented MDS or MDS/MPN; or
• MDS-related cytogenetic abnormalities; or
• Multilineage dysplasia, defined as dysplasia in ≥50% of the cells in ≥2 myeloid cell lines, excluding NPM1 or biallelic mutation of CEBPA

In patients without prior diagnosis of MDS or MDS/MPN, additional morphologic and genetic analyses, including bone marrow aspirate, cytogenetic analysis with karyotype or FISH, and molecular testing, may be needed for an accurate diagnosis of AML-MRC.

In patients with a history of MDS, approximately 30% of these cases will progress to AML-MRC.

So in my experience, patients with therapy-related AML or AML-MRC represent among the most challenging group of patients to treat. Often these patients have had a prior malignancy, often hematologic, which has left them with poor cytopenias going into their treatments. And, often the patients who have had established diagnoses of MDS or MDS/MPN have received treatments with agents, such as hypomethylating agents, which may make them already with a significant amount of cytopenias. In addition, the cytogenetics and chromosomal changes of these patients is often higher risk and requires really looking to identify who are these high-risk patients, looking for things like higher percentages of blasts, and looking for things like high-risk cytogenetic and molecular features, which might help predict who are the patients who are really going to respond poorly to conventional treatment.