KMT2A-Partial Tandem Duplication Associates With Leukemia Transformation in Myelodysplastic Syndrome.

BACKGROUND: Partial tandem duplication of KMT2A (KMT2A-PTD) is observed not only in acute myeloid leukemia (AML) but also in myelodysplastic syndrome (MDS), while the prognostic value of KMT2A-PTD in MDS needs to be clarified and the optimal therapies for these patients remains unclear. METHODS: In this study, we analyzed 137 MDS patients with KMT2A-PTD from our hospital (PKUPH cohort) and incorporated 2493 MDS patients from the International Working Group for Prognosis in MDS (IWG-PM) cohort, among whom 65 patients had KMT2A-PTD. RESULTS: MDS patients with KMT2A-PTD in IWG-PM cohort had significantly higher blast percentage and IPSS-R score than those without KMT2A-PTD. The 3-year cumulative incidence of leukemia transformation in MDS patients with KMT2A-PTD from both PKUPH and IWG-PM cohort was significantly higher than that in MDS patients without KMT2A-PTD (49.8% [95% CI, 38.6%-61.1%] vs. 19.3% [95% CI, 17.5%-21.2%], P < .001; 58.3% [95% CI, 43.1%-73.5%] vs. 19.3% [95% CI, 17.5%-21.2%], P < .001), respectively. Multivariate analysis in the IWG-PM cohort showed that KMT2A-PTD was an independent poor predictor for leukemia transformation (P < .001). None of co-occurring gene mutations significantly influenced the risk of leukemia transformation in MDS patients with KMT2A-PTD. A landmark analysis in PKUPH cohort suggested that allogenic hematopoietic stem cell transplantation (allo-HSCT) significantly reduced the cumulative incidence of leukemia transformation (P < .001) and the cumulative incidence of relapse (17.6% [95% CI, 5.1%-28.7%] vs. 100% [95% CI, 51.0%-100%], P < .001), respectively. CONCLUSION: KMT2A-PTD may identify a distinct MDS subgroup characterized by a high risk of leukemia transformation, and allo-HSCT could improve outcomes of MDS patients with KMT2A-PTD.