BACKGROUND: Data on bone marrow (BM) findings in secondary hemophagocytic lymphohistiocytosis (sHLH) and their association with overall survival (OS) are limited. OBJECTIVES: This study aimed to develop a prognostic model incorporating BM findings and clinico-laboratory factors affecting OS. METHODS: We retrospectively evaluated 50 adults with sHLH and developed a clinicopathological prognostic model based on survival-associated factors. RESULTS: Most patients demonstrated normocellular BM (46.3%) and mild hemophagocytic activity (44.2%). Factors associated with survival in multivariable analyses (MVA) were age above 70 years (hazard ratio [HR] 3.89, p = 0.016), infection-related (HR 4.62, p = 0.006), hemoglobin <
7 g/dL (HR 5.21, p <
0.001), and hypocellular marrow (HR 3.07, p = 0.04). A clinicopathological HLH risk model assigned 1 point to each MVA-identified survival factor, categorizing patients into low- (score 0-1), intermediate- (score 2-3), and high-risk (score 4) groups. The 6-month OS from bootstrapping internal validation among the low-, intermediate-, and high-risk groups were 84.2%, 55.6% (p <
0.001) and 7.7% (p <
0.001), respectively. The area under the receiver operating characteristic curve (AuROC) was 0.87. CONCLUSIONS: This model stratified sHLH patients into three risk groups with distinct survival outcomes, potentially guiding future therapy.