Mast Cell Leukemia Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Background

Mast cell leukemia (MstCL) is a rare but aggressive variant of systemic mastocytosis (SM) which is defined by the presence of >20% atypical mast cells in the bone marrow. It is further classified into leukemic and aleukemic variants based on the presence or absence of >10% atypical mast cells in the peripheral blood, respectively. There is a wide variation in treatment regimens used to treat MstCL. Despite this, the prognosis remains poor. The determinants of survival outcomes in this disease are not very well defined. Therefore, we conducted this pooled database analysis to identify the prognostic factors, clinicopathological characteristics, and therapeutic strategies that influence survival in this disease.

Methods

To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 144 cases that fit the diagnostic criteria for MstCL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS).

Results

A total of 144 patients with confirmed MstCL were identified. The median age was 58.5. There was a slight female preponderance with F:M of 1.2. The median duration of symptoms before diagnosis was 2 months. Involvement of lymph nodes, spleen, peripheral blood, skin, and CNS occurred in 17%, 44%, 23%, 13%, and 6%, respectively. Constitutional symptoms and hemophagocytosis occurred in 33% and 8% of the cases, respectively. The median OS and DFS of the whole group were 9 and 8 months, respectively. Patients younger than 55 had worse median OS (6 vs. 15 months, p=0.03). Hgb<10g/dl (p=0.0002), Platelets<100K (p=0.01), leukemic phase (p=0.02), and complex cytogenetics (p=0.02) were associated with worse OS. Furthermore, presence of hemophagocytosis had worse OS (p=0.06). Although the presence of constitutional symptoms, Tryptase>200, and KIT mutations other than D816V had numerically worse OS, they did not reach statistical significance. Sex, IHC phenotype, presence of concomitant malignancy, and type of organ involvement did not impact OS. Compared to no treatment, dose-intense chemotherapy, non-dose-intense chemotherapy, novel agents, and stem cell transplant had incrementally superior OS (2 vs. 7 vs. 15 vs. 15 vs. 23 months, p<0.0001). Patients who attained CR as their best response also had a superior median OS compared to responses less than CR and non-responders (NR vs. 29 vs. 8 months, p<0.0001).

Conclusion

This study presents updated clinicopathologic data from a large, pooled cohort of patients with MstCL. It identifies age, anemia, thrombocytopenia, leukemic presentation, complex cytogenetics, type of therapy, and quality of response to treatment as critical determinants of OS.