Until recently, the term “secondary leukemia” broadly included any AML with a history of prior malignancy as well as patients with any antecedent hematologic disorder and, in some series, any patient who presented with unfavorable cytogenetics.

Among therapy-related AML patients, 70% present with abnormalities of chromosome 5 or 7, which is the most typical presentation after the exposure to alkylating agents and/or ionizing radiation; 30% are those that arise after treatment with topoisomerase-2 inhibitors.

In general, the management of therapy-related AML is fraught with uncertainty because, among other reasons, most early studies included small numbers of patients and were retrospective. There have been no prospective randomized studies specifically directed at the treatment of therapy-related leukemias. Furthermore, the published data often included patients with myelodysplastic syndromes.

Induction Therapy

Hisytorically, it was presumed that every patient with therapy-related leukemia had an adverse prognosis and that standard induction therapy was inappropriated. However, there is no evidence that any induction therapy is superior to the standard 3+7 regimen. Among young adults, quite remarkably, prospective studies report an almost identical CR rate of 55% to 60% for patients treated with recognized unfavorable cytogenetics, and there are no reports that anything is better than this. Standard induction should remain the induction therapy regimen.

Postremission Therapy

Figure 1 AML in Patients Less Than 60 Years of Age.

It is still somewhat controversial whether thearpy-related AML has a prognosis that is intrinsically worse that de novo AML, independent of cytogenetics. In a very large database, the National Cancer Research Institute in Great Britain reported a significantly worse outcome for therapy-related AML than de novo AML, within each cytogenetic risk group (favourable, intermediate, and adverse). But, still, the management of patients with therapy-related AML should be guided by the cytogenetic and molecular features, which is the same as de novo AML.

Although there is a perception that any patient with therapy-related AML should be considered at high risk and referred to an allogeneic transplantation, there is no evidence that the long-term outcome for patients who present with a favorable karotype, with no adverse molecular features, is different from patients with the de novo AML. Thus, such patients with favorable category should not be referred to an allogeneic transplantation in CR1.