Therapy-related acute lymphoblastic leukemia: Where do we stand with regards to its definition and characterization?

Acute lymphoblastic leukemia (ALL) arising in patients with prior malignancy is increasingly being reported. Although terms such as 'secondary' and 'therapy-related' have been interchangeably used to characterize these cases of ALL in a similar fashion to acute myeloid leukemia (AML), it must be noted that some reported cases have not had exposure to cytotoxic therapy and hence a causal relationship between the prior malignancy and subsequent ALL is difficult to establish. Therefore, the use of the term secondary ALL to describe such cases without exposure to cytotoxic therapy is preferably avoided and will not be discussed here. ALL related to prior cytotoxic therapy (t-ALL) appears to be a distinct entity when compared to the de novo ALL, with characteristics including older age at the time of onset, female predominance and leukemia genetics enriched with KMT2A (MLL) gene rearrangement and chromosomes 5/7 abnormalities. Outcome of t-ALL appears inferior to de novo ALL when treated with conventional combination chemotherapy and this adverse outcome may be related to unfavorable patient factors as well as high risk genetic features of the disease itself. Additional genomic and molecular studies are needed to better characterize pathologic features of ALL arising after exposure to cytotoxic therapy in patients with prior malignancies.