Granularity in disease classification impacts survival prediction in advanced systemic mastocytosis: A single institution study of 329 informative cases

Abstract

The 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.

Clinical impact of cytomorphology in mast cell leukemia

“…20 Together, the morphologic assessment of bone marrow smears remains a critical approach in the diagnosis of SM and MCL, as it provides important information regarding the prognosis and variant of MCL. In addition, as has been shown in previous studies 16 and in the recent studies conducted by Pardanani et al, [17][18][19] MC immaturity is an important prognostic variable in MCL. There is also an ongoing discussion whether the basic concept to split MCL into a chronic and acute variant should be reconsidered.…”

“…9,16 The cytomorphological aspects of MCL have been examined in greater detail in three articles published in this issue of the American Journal of Hematology. [17][18][19] In these studies, a more mature MC morphology has been described to correlate with longer overall survival compared with MCL with immature MC morphology (Table 1). [17][18][19] This observation has also been confirmed for patients treated with KIT-targeting tyrosine kinase inhibitors or other drugs.…”

“…[17][18][19] In these studies, a more mature MC morphology has been described to correlate with longer overall survival compared with MCL with immature MC morphology (Table 1). [17][18][19] This observation has also been confirmed for patients treated with KIT-targeting tyrosine kinase inhibitors or other drugs. 18 However, although the prognosis was better in MCL with mature MC morphology, most of these patients progressed and died within a few years despite therapy.…”

“…18 However, although the prognosis was better in MCL with mature MC morphology, most of these patients progressed and died within a few years despite therapy. [17][18][19] One explanation for this phenomenon is that the biology, oncogenic machineries, and driver pathways in MCL with more mature or more immature MC are quite similar or even identical. A more discriminative feature may be MCLinduced organ damage which defines the presence of acute MCL.…”

“…A more discriminative feature may be MCLinduced organ damage which defines the presence of acute MCL. [7][8][9] In this regard, it would be of interest whether some or all patients described in the articles of Pardanani et al 17 and Tefferi et al 18,19 were suffering from chronic MCL (no C-Findings) or acute MCL (C-Findings present). Indeed, as mentioned, MCs are usually more mature cells in chronic MCL compared with patients with acute MCL.…”