Outcome of Patients (pts) with Therapy-Related De Novo Acute Myeloid Leukemia (t-de novo AML): Single Institution Experience

Abstract

Background:Therapy-related myeloid neoplasms develop after cytotoxic chemotherapy or radiation therapy. The available data on the outcome of pts with t-de novo AML without antecedent history of myelodysplastic syndrome (MDS) is limited.Methods:We reviewed the records of pts with newly diagnosed AML who presented to our tertiary care center from 1/2000 to 1/2014. t-de novo AML was defined as having at least 20% blasts in bone marrow with a history of any previous cytotoxic chemotherapy or radiation therapy, and without an antecedent history of MDS. Leukemia-free survival (LFS) was defined as time from achieving complete response (CR) to relapse or death. The overall survival (OS) and LFS in pts with t-de novo AML were compared to those of with de novo AML with normal karyotype (NK) and complex karyotype (CK).Results:Among 1677 pts with newly diagnosed AML, 383 had de novo NK-AML, 218 had de novo CK-AML, and 187 had t-de novo AML. The median follow-up was 9.3 months (range; 0.2-161.0). Pt characteristics and outcomes are described in Table 1. Among the 187 pts, 69 had a history of lymphoma; 63 pts breast cancer (Ca); 10 pts colon Ca; 10 pts sarcoma; 8 pts prostate; 7 pts bladder Ca; 6 pts uterine Ca; 5 pts lung Ca; 5 pts head and neck Ca; 30 pts other type of Ca. Among the pts with t-de novo AML, 15 pts (8%) had a favorable-risk karyotype by WHO, 53 pts (28%) intermediate-risk karyotype, and 119 pts (64%) poor-risk karyotype. The median LFS duration in t-de novo AML, NK-AML, and CK-AML were 7 months (95% confidence interval [CI]; 5.1-8.7), 19 months (95% CI; 13.0-25.2), and 6 months (95% CI; 9.0-13.5) (p<.001), respectively. The median OS duration in t-de novo AML, NK-AML, and CK-AML were 7 months (95% CI; 5.9-8.9), 21 months (95% CI; 16.2-25.5), and 12 months (95%CI; 10.6-13.5) (p<.001), respectively. The results of univariate (UVA) and multivariate analysis (MVA) associated with OS were summarize in Table 1. MVA identified age over 60, white blood cell count (WBC) over 10 x103/µL, thrombocytopenia below 30 x103/µL, non-favorable cytogenetic abnormalities, positive RAS mutation, and the absence of CR or CR with incomplete platelet recovery (CRp) as poor prognostic features related to OS.Conclusion:LFS and OS were shorter in patients with t-de novo AML than in those with NK-AML but did not differ significantly from patients with CK-AML.Abstract 2273. Table 1Patient Characteristics and Outcomest-de novo AML [n= 187]de novo AML with NK [n= 383]de novo AML with CK [n= 218]PAge at diagnosis, median (years)64 (21-89]63 (17-90)67 (18-87)Prior radiation therapy, No. (%)101 (54)00Prior chemotherapy, No. (%)186 (99)00White blood cell count at diagnosis, median (x103/µL)3.2 (0.2-191)4.3 (0.2-390.0)2.9 (0.5-278.2)Hemoglobin at diagnosis, median (g/dL)9.1 (4.5-12.9)9.1 (4-14.6)9.0 (2.5-14.2)Platelet count at diagnosis, median (x103/µL)34 (4-454)51 (3-469)42 (2-319)LDH at diagnosis, median (IU/L)1359 (210-22090)1189 (200-42000)1274 (231-20572)Peripheral blood blast percent at diagnosis, median (%)8 (0-98)9.5 (0-98)10 (0-98)Bone marrow blast percent at diagnosis, median (%)41 (0-96)44 (0-96)33 (0-97)Molecular genetic abnormalities at diagnosis, No. (%)FLT3-ITD17 (9)96 (25)5 (2)FLT3-D8356 (3)23 (6)1 (1)NPM17 (4)104 (27)4 (2)JAK23 (2)6 (2)8 (4)RAS17 (9)50 (13)8 (4)RUNX1-RUNX1T14 (2)00CBFb-MYH6 (3)00Response, No. (%)<0.001Complete response89 (48)237 (62)76 (35)Complete response without platelet recovery15 (8)1 (0)15 (7)1-year LFS, (%)336027<0.0012-year LFS, (%)335220<0.0011-year OS, (%)346830<0.0012-year OS, (%)244613<0.001UVA and MVA of OS in t-de novo AMLUVAMVAHazard ratio95% CIAge at diagnosisAge =< 60 years-Age >60 years< .001.0012.2381.417-3.534White blood cell count (WBC) (x103/µL)WBC =< 10.0-WBC > 10.0.002.0371.6171.030-2.540Hemoglobin (Hgb) (g/dL)Hgb >= 8-Hgb < 8.749Platelet count (Plt) (x103/µL)Plt >= 30-Plt < 30.008.0041.8521.224-2.803LDH (IU/L)LDH =<1000-LDH > 1000.640Peripheral blood blast percent (PB blast)(%)PB blast =< 10%-PB blast >10%.178Bone marrow blast percent (BM blast) (%)BM blast =<40%-BM blast >40%.393Cytogenetic abnormalityFavorable-Non-Favorable.002.0195.8361.342-25.370FLT3-ITDNegative-Positive.768RASNegative-Positive.047.0032.5761.367-4.856ResponseCR or CRp-Non-CR or CRp<.001.009.3310.145-0.757CR-Non-CR<.0010.903.9500.418-2.160 [Display omitted] DisclosuresKantarjian:ARIAD, Pfizer, Amgen: Research Funding.