Induction failure of standardchemotherapy with anthracycline and cytarabine occur frequently in AML.
The aim of this retrospective single centre study was to investigate risk factors for induction failure (IF) of standard chemotherapy with anthracycline and cytarabine (DA) in 108 patients with acute myeloid leukemia (AML), who were consecutively treated between 2013 and 2018 at our institution
We evaluated in all patients at diagnosis CMV igG status, LDH-value, Platelet counts, peripheral blood blast number and blast count in bone marrow, Sorror comorbidity score (range 0–6), age (under 70 years or above), and cytogenetic risk factors according to the ELN classification (favourable [n = 15], intermediate [n = 55], or high risk [n = 38]). Furthermore we evaluated if the occurrence of biclonal AML detected by flow cytometer and extramedullary manifestation of AML are risk factors for IF of standard chemotherapy with DA. IF was defined as non-responsiveness of one induction therapy with ≥ 30% blasts regardless of cellularity or non-achievement of complete remission after two induction therapies. The primary study objective was to identify risk factors for IF after DA therapy in our study cohort. Further, second study objectives were to evaluate rate of overall survival (OS) after salvage chemotherapy and allogeneic transplant in patients with IF.
55 male and 53 female patients were evaluated for IF after DA therapy. In 42 (39%) of 108 patients an IF was observed. Total 37 of these patient received a salvage therapy with idarubicin and fludarabine (n = 29) or allotransplant (n = 8), whereas 5 patients received no further intensive therapy but only best supportive care. Consolidation therapies were in 6 patients high dose cytarabine and in 68 patients allogeneic transplant. By flow cytometer detectable biclonal AML was found in 10 (9,3%) cases, whereas extramedullary manifestation of AML was reported in 8 (7,3%) patients. Both had statistically no influence on the occurrence of IF. Only age above 70-years (p = 0.04, odd ratio 2.5), cytogenetic adverse risk classification according to ELN (p = 0.006; odd ratio 3.21), Sorror comorbidity score of 2 or higher (scores 2–6), (p = 0.019, odd ratio 2.72), and more than 40% blasts in bone marrow (p = 0.01; odd ratio 3.64), had influence on the occurrence of IF after DA. We used for calculation of p-value Mann-Whitney U-test and one-sided Fisher-exact test. Gender, platelet counts under 40.000/nl, peripheral blood blast counts over 20%, positive CMV immunoglobuline G status, LDH above norm at diagnosis had no influence statistically for the occurrence of IF. PFS and OS did not differ statistically between responders and non-responders of induction therapy when an allogeneic transplant subsequently was performed. Patients with IF and without subsequent transplant had a worse prognosis (2-year OS 20% versus 85%, p < = .02). Further reduced OS was found for patients >70 years (2-year OS 50% versus 75%, p < 0.05)
In our study cohort we identify age over 70 years, adverse cytogenetic risk classification according to ELN, Sorror morbidity score of 2 or higher and blast count > 40% in bone marrow as risk factors for primary induction failure after DA chemotherapy in AML. The occurrence of IF had no influence on outcome for patients when after salvage therapy a subsequently an allogeneic transplant was performed.