Chronic Neutrophilic Leukemia With CSF3R Mutation:Two Cases Report And Literature Systemic Analysis

Objective:To explore the clinical characteristic,treatment and outcome of patients with chronic neutrophilic leukemia(CNL).Methods:Two cases of CNL harboring CSF3R mutation who were admitted to Hong Kong University Shenzhen Hospital from 2012 to 2018 were presented.The features of CNL were analyzed by reviewing domestic and foreign literature.Results:The two patients from our hospital:Two male patients were 34-year-old and 74-year-old,respectively.Both harbored the CSF3R-T618I mutation.The young patient complicated with SETBP1?ASXL1 and BCOR mutations received the treatment of ruxolitinib,but it did not work.And he died from graft failure and infection after allogeneic hematopoietic stem cell transplantation(allo-HSCT)at the accelerated phase.The old patient complicated with SETBP1 mutation treated by hydroxyurea and interferon also died for infection.The time from diagnosis to death were 18 months and 30 months respectively for the young and old patient.The results from literature review:The data of 59 CNL cases harboring CSF3R mutation with detailed information which were reported since 2000 was collected.The median age at the time of diagnosis was 65 years(range:1-92).Male to female ratio was 2.2:1.T618I was the most common type of CSF3R mutation,occupying 92%of the 59 patients.The incidence was 73%(27/37)and 49%(25/51)of ASXL1 and SETBP1 mutation,respectively.Most of the patients had received the first-line therapy of hydroxyurea.The second-line therapy including interferon,combined chemotherapy,ruxolitinib and allo-HSCT was also unsatisfactory.Five of 59 patients underwent the allo-HSCT.Three of them who were accelerated or blast crisis phase before HSCT died after HSCT.The remaining two alive patients who were chronic phase before HSCT.The peripheral blood and bone marrow of one patients was normal 6 months after allo-HSCT.The other one was just followed up 35 days after HSCT.The median survival time of 50 patients was 17 months(95%Cl 11.2-22.7 months).WBC>50�109/L(P=0.002)and ASXL1 mutation(P=0.009)were associated with poor outcome.While PLT<100�109/L(P=0.306)or SETBP1 mutation didn't affect the overall survival.Conclusion:1.CNL mainly developed in elderly patients with male preponderance.The median age at diagnosis was 65 years.2.T6181 was the most common type of CSF3R mutation.CSF3R mutation was commonly complicated with ASXL1 and SETBP1 mutation in CNL patients.3.There was no standard treatment for CNL.Early allo-HSCT might improve the prognosis of the young patients.4.The overall survival time of CNL was about 17 months.WBC>50�109/L and ASXL1 mutation were related to the poor outcome.