Secondary acute myeloid leukemia (s‐AML) patients have a poor prognosis and currently the only curative therapy is allogeneic stem‐cell transplant (HSCT). However, we do not yet know whether transplantation is sufficient to reverse the poor prognosis compared to de novo AML patients. We analyzed survival after HSCT comparing a cohort of 58 patients with s‐AML versus 52 de novo patients who were transplanted between 2012 and 2020. Patients with s‐AML had worse event‐free survival (EFS) (p = 0.001) and overall survival (OS) (p < 0.001) compared to de novo AML due to an increased risk of relapse (p = 0.06) and non‐relapse mortality (p = 0.03). The main difference in survival was observed in patients who achieved complete remission (CR) before HSCT (EFS p = 0.002 OS and <0.001), regardless minimal residual disease (MRD) by |multiparametric flow cytometry cohorts. In patients transplanted with active disease (AD), the prognosis was adverse in both s‐AML and de novo AML groups (EFS p = 0.869 and OS p = 0.930). After excluding patients with AD, we stratified the cohort according to conditioning intensity, noticing that s‐AML who received MAC had comparable outcomes to de novo AML, but the survival differences remained among reduce intensity conditioning group. In conclusion, transplanted s‐AML patients have worse survival among patients in CR before HSCT, regardless of MRD level by flow cytometry compared to de novo AML. MAC patients had similar outcomes irrespective of leukemia ontogeny.
Acute myeloid leukemia (AML) is the most common acute leukemia in the adult population and largely affects older patients with a median age at diagnosis of 68 years. 1 Elderly patients with AML often respond poorly to induction chemotherapy as a result of higher frequency of adverse genome features and increased resistance to treatment. 2,3 Furthermore, because of comorbidities, compromised organ function, and poor performance status, older patients may not be candidates for conventional cytotoxic induction therapies, 2,4-6 and therefore, treatment options for unfit patients have historically been limited. 7 Less intensive approaches to treatment, such as low-dose cytarabine (LDAC), have shown poor response rates (11%-19%) and short median survival rates (<6 months). 8,9 Similarly, hypomethylating agents (HMA) azacitidine and decitabine in monotherapy are associated with a tolerable safety profile, complete remission (CR) plus CR with incomplete count recovery (CRi) rates of 15%-30%, and median overall survival (OS) of <12 months. 10,11 In November 2018, the Food and Drug Administration (FDA) approved the selective BCL-2 inhibitor venetoclax in combination with either HMA or LDAC in older or unfit patients with AML. 7 Venetoclax has shown encouraging activity when combined with HMA agents. 2,12 Venetoclax 400 mg plus HMA (Ven/HMA) in newly diagnosed AML patients without prior HMA exposure led to a 73% rate of CR + CRi, 2 while, in relapsed/refractory (r/r) AML patients (61% with prior HMA failure), it was observed with an ORR (CR + CRi) of 51%. 12 The combination is well-tolerated even in fragile
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.