Poster Session II: Acute myeloid leukemia - Clinical
Chromosome 17 (ch17) abnormalities, especially loss of the 17p region and P53 gene mutations (p53mut) result in very low rates of cure for patients with acute myeloid leukemia (AML) treated with conventional chemotherapy or allogenic stem cell transplant (ASCT).
We assessed whether such poor outcomes extend to patients with all types of ch17 abnormalities and whether p53mut has further prognostic value.
We retrospectively analyzed 98 patients at our institution with AML/myelodysplastic syndrome (MDS) who had ch17 abnormalities noted on cytogenetics. p53mut was analyzed by next generation sequencing (NGS).
61 patients with AML and 37 patients with MDS were included. Patient characteristics are in Table 1. 95 out of the 98 patients had 17p abnormalities as part of a complex karyotype, whereas 67 out of the 98 patients had a monosomal karyotype.
Complete remission (CR) with first line treatment was similar between induction chemotherapy or hypomethylating agents, 22.9% vs 21.6 % (p = 0.33).
Median overall survival (OS) for all patients was 10 months. Ch17 abnormalities were classified into those resulting in deletion of the p53 loci such as 17p deletion and monosomy 17 (17pdel/mono17) and all other ch17 abnormalities (ch17oth). Amongst patients with 17pdel/mono17with NGS available, 19 of 26 had p53mut, while for ch17oth, 13 of 17 had p53mut (p = 0.72).Patients having both p53mut and abnormal ch17 exhibited poorer OS compared to patients with no p53mut (10 vs 23 months, p = 0.02).
30 patients (19 AML, 11 MDS) underwent ASCT, with a median post-transplant OS of 11 months. For AML ASCT patients, 18 were in CR (13 with cytogenetic remission) and 1 had refractory disease at transplant, whereas for MDS patients, 3 were in CR (2 with cytogenetic remission) and 8 had stable disease. The post-ASCT survival between AML/MDS cohorts did not differ (p = 0.6), although cytogenetic CR at time of ASCT trended towards improved OS (17 vs 8 months; p = 0.6). At last follow-up, only 5 of 30 patients were alive, 4 in CR.
AML/MDS patients with all types of ch17 abnormalities have a poor prognosis with or without ASCT, representing a distinct subset of patients amongst that that have complex cytogenetics. TP53 abnormalities detected by NGS are not limited to patients with 17pdel/mono17 and can be seen with other ch17 abnormalities. Drugs targeting the TP53 pathway and improving depth of response prior to ASCT are needed for improved outcomes in these patients.