Mutations in the additional sex combs like 1 gene (ASXL1) have been described recently in patients with myelodysplastic and myeloproliferative syndromes. While in MDS ASXL1 is associated with worse prognosis, the role in MPN is not well defined. The aim of this study was to investigate the prognostic impact of ASXL1 mutations in 136 patients with primary myelofibrosis or post ET/PV myelofibrosis who underwent allogeneic stem cell transplantation after reduced intensity conditioning.
Out of 136 patients sufficient genomic DNA prior transplantation was available for 103 patients. The median age of 48 female and 55 male patients was 59 years (range, 33–75y). After busulfan (n= 97) or treosulfan (n=6) based dose-reduced conditioning, patients received a stem cell graft from a related (n= 17) or unrelated donor (n=48). ASXL1 was sequenced by Sanger sequencing, and positive patients were confirmed by an independent sequence analysis.
Mutations in ASXL1 were found in 27 patients (26%), of whom 24 had frameshift mutations (23%). ASXL1 mutated and non mutated patients were equally distributed between patients with unrelated (19% pos/81% neg) and related (21% pos/79% neg) donors. ASXL1 mutations were found at the same frequency in Lille low risk (15%), intermediate risk (24%) and high risk (20%) patients.
After a median follow up of 41 months (range 26–62) the cumulative incidence of non- relapse mortality at 1 year and relapse at 5 years were 26% (95% CI 16–36) and 26% (95% CI 16–36), respectively, and the 5-year OS was 56% (95% CI 44–68).
Patients with ASXL1 mutation did not differ significantly to those without mutation in non relapse mortality (35% vs. 22% p=0.4), relapse incidence (24% vs. 27%, p=0.9) and regarding overall survival. Overall survival for ASXL1 mutated and wildtype patients was not significantly different (47% vs. 59%, p= 0.5) in patients with any ASXL1 mutation and in the subgroup of ASXL1 frameshift mutated patients (48% vs. 59%, p= 0.6). The rates of acute grade II-IV GvHD and of chronic GvHD were similar in ASXL1 mutated and wildtype patients (44% vs. 36%, p=0.5 and 52% vs. 46%, p=0.7, respectively). In summary, ASXL1 is one of the most frequently mutated genes in PMF patients. Patients with ASXL1 mutations have a similar outcome after dose reduced allogeneic HSCT as patients with wildtype ASXL1.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.