IMPACT OF KIT MUTATIONS IN ACUTE MYELOID LEUKAEMIA WITH INV(16)

Several studies have recently pointed out the adverse impact of KIT mutations (mutKIT) on relapse incidence (RI) and overall survival (OS) in patients with t(8;21) AML. By contrast, the prognostic significance of mutKIT in patients with inv(16) remains unclear. Aims. Purpose of this study is to evaluate the prevalence and the effect on outcome of mutKIT in inv(16)(p13q22). Patients and Methods. 50 adults with inv(16) AML at diagnosis (median age 46.6 years, range: 17-88; M/F: 30 /20), were centrally analyzed for mutKIT in exon 2, 8, 10, 11 and 17. Mutations were detected using sequencing and other sensitive assays such as ARMS (amplification refractory mutation system) PCR for D816Y and D816H, enzymatic digestion with HINFI for D816V and with Tsp509I for N822K. Results. KIT mutations were documented in 17/50 patients (34%). Among the mutKIT cases, we detected mutations in exon 17 (n=12), exon 8 (n= 4) and exon 10 (n=1). We found no significant difference between the mutKIT vs the unmutated (KIT-) patients in WBC count at presentation (WBC 13.9x109/Liter, range 4.4 to 277.5 vs 19.4x109/Liter, range 2.5 to 130; Mann-Whitney U test: p=0.649). 42 patients (age <60 years) received intensive chemotherapy; of them, 13 resulted mutKIT upon mutational screening. CR was achieved in 13 of 13 mutKIT patients (100%) vs 27 of 29 KIT-patients (93%), (Fisher’s exact test: p>0.999). With a median follow-up of 26 months (range: 2 to 147), the Kaplan-Meier plots showed a worse RI among the mutKIT vs the KIT- patients (log-rank test: p=0.04; Figure 1). We didn't observe any difference in OS between the two groups of patients (log-rank test: p=0.44).