Acute Megakaryocytic Leukemia Clinicopathologic Determinants of Survival: Analysis of a Pooled Database
Authors: Haddad Philip A , Vutukuri Sireesha , Gupta Ankita 
Published: December 2024

Background
Acute megakaryocytic leukemia (AMKL) is a rare and aggressive form of acute myeloid leukemia (AML) that predominantly involves the malignant proliferation of megakaryoblasts. It comprises less than 1% of all AML cases in adults and a higher proportion in pediatric patients, particularly those with Down syndrome. AMKL presents unique diagnostic and therapeutic challenges due to its distinct clinical and biological characteristics. AMKL's overall prognosis remains poor. The determinants of survival outcomes in this disease are not very well defined. Therefore, we conducted this pooled real-world database analysis to identify the prognostic factors, clinicopathological characteristics, and therapeutic strategies that influence survival in this rare disease.
Methods
To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, prognostic factors, and survival, we compiled a pooled database of cases that satisfy the diagnostic criteria for AMKL. 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 220 patients with confirmed AMKL were identified. The median age was 3. There was a male preponderance with M:F of 1.3 in the whole cohort, which differed when analyzed by pediatric (M:F of 1) vs. adult (M:F of 2) subgroups. The median duration of symptoms before diagnosis was 1 month. Constitutional symptoms, lymphadenopathy, splenomegaly, hepatomegaly, and bone involvement were present in 40%, 19%, 34%, 26%, and 13% of the cases, respectively. The median OS of the cohort was 13 months (Pediatrics 44 vs. Adults 5.9, p&lt;0.0001). Those who presented with constitutional symptoms (p=0.05), lymphadenopathy (p=0.06), or LDH&gt;500 U/L (p=0.07) had worse OS of borderline statistical significance. However, patients with Down's Syndrome experienced better OS (NR vs 12 months, p=0.01). Those whose blasts stained positive for CD4 (&lt;0.0001), CD7 (p=0.04), or CD13 (p=0.03) also had better OS. Sex, levels of WBC, Hgb, and Platelets, t(1;22), inv(16), and splenomegaly did not impact OS. However, AMKL, which developed in the context of malignancy or myeloproliferative disorders, was associated with worse OS (p&lt;0.0001). Compared to no treatment, chemotherapy and stem cell transplant had incrementally superior OS (1.5 vs. 10 vs. 23 months, p&lt;0.0001). Those who received low-intensity regimens had an OS similar to that of those untreated. Furthermore, patients who achieved CR as their best response also had a superior median OS (44 vs. 4 months, p&lt;0.0001).
Conclusion
This study presents updated clinicopathologic data from a large, pooled cohort of patients with AMKL. It identifies age, presence of Down's Syndrome, occurrence in the context of malignancy or myeloid disorders, intensity of therapy, and quality of response to treatment as critical determinants of OS.