Contributions
Abstract: PB2085
Type: Publication Only
Background
Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms characterized by aberrant myeloid differentiation, ineffective hematopoiesis and potency of secondary acute myeloid leukemia (sAML) progression. The underlying mechanism of this transformation has long been the hit topic among hematologists. Besides, with the nature of heterogeneity seen in MDS, scoring systems were introduced to evaluate the prognosis of patients with MDS, such as IPSS-R, yet leaving molecular patterns out of them. Meanwhile, the role of FLT3 gene in AML has been well documented and put into practice. Nevertheless, with a rather low incidence of mutation in MDS group (0.6%>6%), the role of FLT3 mutation has not been revealed fully in real world MDS.
Aims
The present study was performed to investigate: the mutation patterns of FLT3 in MDS among Chinese patients; the impact of FLT3 on prognosis of Chinese MDS patients; and the association between FLT3 mutations and secondary AML transformation.
Methods
311 de novo MDS patients diagnosed between 2010 and 2016 under the 2016 WHO criteria were enrolled, with written informed consent. Studies were approved by the ethics committee of the First Affiliated Hospital of Soochow University (FAHSU) in accordance to the declaration of Helsinki protocol. FLT3 testing was applied only at initial diagnosis and at the first time of AML progression. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, which were adjusted for possible confounding factors.
Results
The mutation patterns of FLT3-ITD seen in our patients were similar with their AML counterparts. With basic clinical characteristics well balanced, leukemia transformation rate was significantly different between FLT3-ITD and wild type groups, with 42.9% (3/7) and 10.2% (31/304) of each. Two groups also showed diverse prognosis. The progression free survival (PFS) was 43(16-310) days and 365(8-2208) days in ITD positive and negative group, respectively(P<0.001). And the overall survival (OS) was 218(16-334) days and 414(8-2208) days (P<0.001). In later univariate and multivariate analysis, five factors were found having independent impact on OS: bone marrow blast percentage, WBC count, cytogenetics subtype, treatment and FLT3-ITD mutation status. Here the treatment was graded into three parts, transplantation, chemotherapy or demethylation agents and supportive care only.
Conclusion
When observed at MDS stage, patients harboring FLT3-ITD mutations had higher AML-transformation rate, quicker disease progression and shorter survival than wild type patients among Chinese population, laying in accordance with data from previous studies.
Session topic: 10. Myelodysplastic syndromes – Clinical
Keyword(s): Flt3-ITD, MDS
Abstract: PB2085
Type: Publication Only
Background
Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms characterized by aberrant myeloid differentiation, ineffective hematopoiesis and potency of secondary acute myeloid leukemia (sAML) progression. The underlying mechanism of this transformation has long been the hit topic among hematologists. Besides, with the nature of heterogeneity seen in MDS, scoring systems were introduced to evaluate the prognosis of patients with MDS, such as IPSS-R, yet leaving molecular patterns out of them. Meanwhile, the role of FLT3 gene in AML has been well documented and put into practice. Nevertheless, with a rather low incidence of mutation in MDS group (0.6%>6%), the role of FLT3 mutation has not been revealed fully in real world MDS.
Aims
The present study was performed to investigate: the mutation patterns of FLT3 in MDS among Chinese patients; the impact of FLT3 on prognosis of Chinese MDS patients; and the association between FLT3 mutations and secondary AML transformation.
Methods
311 de novo MDS patients diagnosed between 2010 and 2016 under the 2016 WHO criteria were enrolled, with written informed consent. Studies were approved by the ethics committee of the First Affiliated Hospital of Soochow University (FAHSU) in accordance to the declaration of Helsinki protocol. FLT3 testing was applied only at initial diagnosis and at the first time of AML progression. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, which were adjusted for possible confounding factors.
Results
The mutation patterns of FLT3-ITD seen in our patients were similar with their AML counterparts. With basic clinical characteristics well balanced, leukemia transformation rate was significantly different between FLT3-ITD and wild type groups, with 42.9% (3/7) and 10.2% (31/304) of each. Two groups also showed diverse prognosis. The progression free survival (PFS) was 43(16-310) days and 365(8-2208) days in ITD positive and negative group, respectively(P<0.001). And the overall survival (OS) was 218(16-334) days and 414(8-2208) days (P<0.001). In later univariate and multivariate analysis, five factors were found having independent impact on OS: bone marrow blast percentage, WBC count, cytogenetics subtype, treatment and FLT3-ITD mutation status. Here the treatment was graded into three parts, transplantation, chemotherapy or demethylation agents and supportive care only.
Conclusion
When observed at MDS stage, patients harboring FLT3-ITD mutations had higher AML-transformation rate, quicker disease progression and shorter survival than wild type patients among Chinese population, laying in accordance with data from previous studies.
Session topic: 10. Myelodysplastic syndromes – Clinical
Keyword(s): Flt3-ITD, MDS