Treatment patterns and outcomes of 2310 patients with secondary acute myeloid leukemia: a PETHEMA registry study

Abstract

Secondary acute myeloid leukemia (sAML) comprises a heterogeneous group of patients, and is associated with poor overall survival (OS). We analyze the characteristics, treatment patterns and outcomes of sAML adult patients of the Programa Español de Tratamientos en Hematología (PETHEMA) registry. Overall, 6211 (72.9%) were de novo and 2310 (27.1%) sAML, divided into myelodysplastic syndrome (MDS-AML, 44%), MDS/myeloproliferative (MDS/MPN-AML, 10%), MPN-AML (11%), therapy-related (t-AML, 25%), and antecedent neoplasia without prior chemotherapy/radiotherapy (neo-AML, 9%). Compared to de novo, sAML were older (median age 69 years old), had more ECOG ≥2 (35%) or high-risk cytogenetics (40%), less FLT3-ITD (11%) and NPM1 mutations (21%), and received less intensive chemotherapy regimens (38%) (all P<0.001). Median OS was higher in de novo than in sAML (10.9 vs 5.6 months, P<0.001); and shorter in sAML after hematologic disorder (MDS, MDS/MPN or MPN) as compared to t-AML and neo-AML (5.3 vs 6.1 vs 5.7 months, respectively, P=0.04). After intensive chemotherapy, median OS was better among de novo and neo-AML patients (17.2 and 14.6 months). No OS differences were observed after hypomethylating agents according to type of AML. sAML was as an independent adverse prognostic factor for OS. We confirm high prevalence and adverse features of sAML and we establish its independent adverse prognostic value. This study was registered at www.clinicaltrials.gov as #NCT02607059.

Interaction between myelodysplasia-related gene mutations and ontogeny in acute myeloid leukemia: an appraisal of the new WHO and IC classifications and ELN risk stratification

“…The designation of ontogeny as either MR-Hx/MR-CG or t-AML has clinical implications. Many studies have shown that "secondary" AML, mostly MR-Hx/MR-CG and t-AML, is associated with an inferior outcome with or without allo-HSCT 16,33,34,[36][37][38][39][40] . Our study has confirmed these findings by showing MR-Hx, MR-CG and t-AML all confer worse outcomes than de novo AML even after adjusting for age, treatment, transplant, and ELN risks.…”

Chronic Neutrophilic Leukemia: A Comprehensive Review of Clinical Characteristics, Genetic Landscape and Management

“…Conventional chemotherapy with anthracycline and cytarabine (3 + 7) might represent a treatment option for patients transforming to AML; however, overall survival is relatively poor, as expected for secondary AML ( 92 ). Regarding CNL in chronic phase, intensive chemotherapy is not recommended as it is accompanied by high treatment-related mortality and the majority of patients are refractory to this approach ( 11 , 89 ).…”

Role of Pharmacogenetics in the Treatment of Acute Myeloid Leukemia: Systematic Review and Future Perspectives

“…It is important to highlight that there is no consensus on medical suitability criteria and there is no upper age limit. However, caution should be exercised when considering classical intensive therapy for patients older than 75 years, as most of the outcome data related to intensive antileukemic therapy come from studies in younger and fitter adults [ 10 ]. Treatment selection for these patients contemplates hypomethylating agents (decitabine or azacitidine), low-dose cytarabine, and, when possible, BCL2 apoptosis regulator (BCL2) inhibitors (venetoclax) or IDH inhibitors [ 11 ].…”