Immunoglobulin light chain (AL) amyloidosis is a systemic disease characterized by the deposition of β-pleated sheets of monoclonal immunoglobulin light chains, predominantly of the κ or λ types, which are secreted by clonal populations of bone marrow plasma cells (1). This condition may occur alongside any immunoglobulin-secreting B-cell neoplasm. Unlike most proteins, which conform to an α-helical structure, the light chain proteins in AL amyloidosis misfold, forming β-pleated sheets that result in multi-organ damage (2). The rarity and complexity of AL amyloidosis pose significant challenges in both diagnosis and treatment, largely due to the limited availability of comprehensive, detailed patient data.

Although therapeutic advances, including proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies such as daratumumab, have improved hematologic responses and organ function in selected patients, the overall prognosis for AL amyloidosis remains unsatisfactory for many (3–5). In particular, cardiac involvement continues to be a major determinant of survival, with advanced cardiac amyloidosis associated with markedly worse outcomes (6, 7). However, even among patients with similar cardiac or hematologic status, survival can vary significantly, suggesting that current prognostic models may not fully capture disease heterogeneity.

To address this gap, we evaluated a range of routinely available clinical and laboratory parameters that are commonly assessed at the time of diagnosis. While variables such as bone marrow plasma cell percentage and cardiac involvement have been individually studied in previous reports (8, 9), others have received limited attention in the context of AL amyloidosis. By re-examining these indicators, this study seeks to explore their prognostic relevance and provide additional insights to support individualized risk stratification. Therefore, this study aimed to evaluate prognostic factors influencing overall survival in patients with AL amyloidosis.

This study analyzed the clinical characteristics and prognostic factors of patients with AL amyloidosis. Our findings highlight several key factors influencing overall survival, including the presence of myeloma, heart failure, higher BMPCs, and specific biomarkers. The significant association between these variables and survival outcomes underscores the importance of early identification and tailored therapeutic strategies in AL amyloidosis management.

Our study indicated a significant association between higher BMPCs and myeloma with poorer survival outcomes in AL amyloidosis patients. This result highlights the potential of BMPCs as a key prognostic biomarker, as elevated BMPC levels could be indicative of more aggressive disease progression. Patients with myeloma had a significantly lower 36-month survival rate compared to those without, confirming its adverse prognostic effect. As a malignancy of plasma cells, myeloma accelerates AL amyloidosis progression by increasing amyloidogenic light chain production and enhancing organ damage (17, 18). Furthermore, the high burden of clonal plasma cells in the bone marrow has been linked to increased amyloid deposition, further exacerbating the progression of the disease (19–21). Our results are consistent with previous studies that demonstrated significantly worse outcomes in patients with concurrent multiple myeloma compared to those with AL amyloidosis alone (17, 22). Recent studies have also suggested that elevated BMPCs, even in the absence of overt multiple myeloma, contribute to disease progression in AL amyloidosis (20, 23). For instance, Tovar et al. (24). demonstrated that patients with BMPCs >10% had significantly higher levels of circulating free light chains and worse cardiac involvement. These findings support the biological relevance of BMPCs in the pathogenesis and progression of AL amyloidosis beyond their prognostic significance.

Our study also revealed a significant correlation between heart failure and increased mortality in AL amyloidosis patients. Heart failure, particularly in the setting of amyloid cardiomyopathy, is a common cause of death in these patients (25–27). This is consistent with previous findings (28–30), which demonstrated that cardiac involvement in AL amyloidosis is a major determinant of survival, with patients presenting with more severe cardiac involvement having significantly lower survival rates. Early detection of cardiac involvement using advanced imaging techniques such as echocardiography and cardiac MRI can aid in better prognostication and help clinicians intervene earlier, potentially reducing mortality rates associated with cardiac amyloidosis.

In this study, we also identified higher FDPs and longer APTT as independent risk factors for death in AL amyloidosis patients. Previous investigations have documented coagulation and fibrinolytic abnormalities in AL amyloidosis. Arahata et al. (31). reported that systemic AL amyloidosis patients often display abnormal coagulation and fibrinolysis features. Elevated levels of FDPs suggest that there is ongoing fibrinolysis within the body, which may be indicative of a systemic inflammatory response (32). In the context of AL amyloidosis, this heightened fibrinolytic activity is likely a consequence of amyloid deposits triggering a state of chronic inflammation and tissue damage. This chronic inflammation can, in turn, disrupt normal coagulation pathways, potentially increasing the risk of clotting and bleeding disorders (33, 34). Moreover, clotting alterations including prolonged APTT have been observed in AL amyloidosis patients, as evidenced by studies such as that by Gamba et al. (35), which found prolonged aPTT in a cohort of patients with primary systemic amyloidosis. Prolonged APTT could suggest a dysfunction in the coagulation cascade. In the case of AL amyloidosis, amyloid deposits in the vasculature and various organs might directly impair the normal function of coagulation factors or endothelial cells, leading to an increased risk of both hemorrhagic and thrombotic events. Amyloid fibrils can affect the vascular integrity, causing endothelial dysfunction, and might also interact with blood coagulation factors, resulting in a disrupted clotting process (36). These dysfunctions may exacerbate the already existing clinical challenges faced by AL amyloidosis patients, who are often dealing with multiple organ involvement and an unpredictable disease course (35, 37).

Taken together, these findings underscore the complexity of AL amyloidosis, as it is a multifaceted disease where not only the immune system and amyloid deposition drive organ failure, but the coagulation system is also intricately involved in the disease’s progression. The presence of dysregulated coagulation markers like elevated FDPs and prolonged APTT highlights the need for comprehensive management strategies that address not only the underlying plasma cell dyscrasia but also the associated coagulopathy. Monitoring coagulation parameters in AL amyloidosis patients may offer valuable insights into disease severity, help predict adverse outcomes, and guide clinicians in providing tailored treatments aimed at managing both the amyloidogenic process and the systemic effects of the disease, including its impact on coagulation. Moreover, these findings suggest that future therapeutic strategies may need to consider anticoagulation or antifibrinolytic therapies, particularly in high-risk patients with significant coagulopathy, to mitigate the adverse effects of amyloid-induced coagulopathy.

This study provides valuable insights into the clinical characteristics and prognostic factors of AL amyloidosis, emphasizing the importance of BMPCs, heart failure, and light chain differences as key predictors of survival. However, several limitations need to be acknowledged. First, the relatively small sample size may limit the generalizability of the findings, and larger, multicenter studies are needed to validate these results across a more diverse population. Second, due to the retrospective design and limited number of evaluable cases, treatment regimens were not included in the multivariable survival analysis. The heterogeneity in treatment approaches and the relatively early enrollment of many patients before the widespread use of daratumumab further limited our ability to assess treatment-specific effects. Future prospective studies with standardized treatment protocols will be essential to better elucidate the prognostic impact of therapeutic strategies. Third, quantitative cardiac biomarkers such as N-terminal pro-B-type natriuretic peptide and cardiac troponin I/T were not routinely available in our dataset. These biomarkers are central to the Mayo staging system, which is widely used for prognostic stratification in AL amyloidosis. Lastly, the absence of complete immunoglobulin heavy chain subtype data in our cohort prevented a detailed analysis of the associations between IgG subclasses and organ-specific involvement. Considering the potential relationship between immunoglobulin isotypes and the tropism of amyloid deposition, future multicenter studies incorporating standardized immunophenotyping are warranted to determine whether specific subtypes are linked to distinct patterns of organ damage. Despite these limitations, our findings highlight the need to refine current risk stratification models by incorporating additional biomarkers and accounting for disease heterogeneity. Further research is also warranted to investigate the role of emerging treatments such as daratumumab in high-risk populations to optimize patient outcomes.