From Static Diagnosis to Clonal Kinetics: A New Framework for Timing Allogeneic Stem Cell Transplantation in Patients with Bone Marrow Failure Syndromes—A Hypothesis-Generating Case Series

na li^1,2li huang^1,2*

• ¹Hainan General Hospital, Haikou, China
• ²Hainan Medical University, Haikou, China

This retrospective study analyzed four patients with bone marrow failure (BMF) syndromes to evaluate a hypothesis for guiding allogeneic hematopoietic stem cell transplantation (allo-HSCT) based on clonal dynamics. Accurate early subclassification of BMF remains challenging, and conventional diagnosis—often reliant on static, cross-sectional assessment of clonal evolution—frequently results in delayed intervention. Case analyses indicated that serial monitoring of clonal kinetic parameters, may help identify the essential progression toward clonal hematopoiesis (e.g., myelodysplastic syndrome/MDS) earlier than traditional approaches. The presented cases could be considered that even when the initial diagnosis is ambiguous or considered "low-risk," the emergence of progressive clonal signals—such as a steadily rising ring sideroblast (RS) percentage following immunosuppressive therapy (IST) failure—may serve as a compelling indicator to actively consider transplantation. Conversely, delay in intervention may lead to missed therapeutic opportunities. We put forward a hypothesis that, in cases of refractory cytopenia unresponsive to IST, transplant decision-making may benefit from dependence on a "static diagnostic label" to an emphasis on "dynamic disease behavior." Integrating clonal kinetics monitoring into routine clinical management and prospectively evaluating transplant timing based on its trends may help improve patient outcomes.