Citations

AbstractThe World Health Organization (WHO) classification system categorizes advanced systemic mastocytosis (SM‐Adv) into aggressive SM (ASM), mast cell leukemia (MCL), and SM with associated hematological neoplasm (SM‐AHN). By contrast, the International Consensus Classification (ICC) requires “immature” MC cytomorphology for the diagnosis of MCL and limits SM‐AHN to myeloid neoplasms (SM‐AMN). The current study includes 329 patients with SM‐Adv (median age 65 years, range 18–88; males 58%): WHO subcategories SM‐AHN (N = 212; 64%), ASM (N = 99; 30%), and MCL (N = 18; 6%); ICC subcategories SM‐AMN (N = 190; 64%), ASM (N = 99; 33%), and MCL (N = 9; 3%); WHO‐defined MCL with “mature” MC cytomorphology and SM‐AHN associated with lymphoid neoplasms were operationally labeled as “MCL‐mature” (N = 9) and SM‐ALN (N = 22), respectively, and distinguished from ICC‐defined MCL and SM‐AMN. Multivariable analysis that included the Mayo alliance risk factors for survival in SM (age >60 years, anemia, thrombocytopenia, increased alkaline phosphatase) revealed more accurate survival prediction with the ICC versus WHO classification order: (i) survival was significantly worse with MCL‐immature versus MCL‐mature (hazard ratio [HR] 15; p < .01), (ii) prognostic distinction between MCL and SM‐AHN/AMN was confirmed in the context of ICC (HR 9.3; p < .01) but not WHO classification order (p = .99), (iii) survival was similar between MCL‐mature and SM‐AMN (p = .18), and (iv) SM‐AMN (HR 1.7; p < .01) but not SM‐ALN (p = .37) was prognostically distinct from ASM. The current study provides evidence for the independent prognostic contribution of both the ICC system for SM‐Adv and the Mayo alliance risk factors for survival in SM.

SummaryVenetoclax (VEN) is an FDA‐approved selective inhibitor of B‐cell leukaemia/lymphoma‐2 (BCL‐2), used for treating elderly or unfit acute myeloid leukaemia (AML) patients unable to undergo intensive chemotherapy. Combining VEN with hypomethylating agents (HMAs) has shown impressive response rates in high‐risk myelodysplastic syndromes (MDS) and relapsed/refractory AML. However, the efficacy of VEN and HMAs in treating DDX41‐mutated (mDDX41) MDS/AML patients remains uncertain. Despite the favourable prognostic nature of mDDX41 MDS/AML patients, there is a lack of clinical experience regarding their response to different treatment regimens, leading to an unknown optimal therapeutic approach.