Precursor Hematologic Conditions: Diagnosis, Risk Stratification, Clinical Implications, and Management

Hematologic precursor conditions include monoclonal gammopathy of undetermined significance (MGUS), monoclonal B-cell lymphocytosis (MBL), and clonal hematopoiesis (CH). These conditions are characterized by a clonal expansion of either plasma cells, lymphoid cells, or myeloid cells without meeting criteria for active hematologic malignancy and are considered premalignant conditions. Diagnosis of these precursor conditions often occur incidentally based on abnormalities on routine laboratory assessments, such as an elevated globulin level leading to diagnosis of MGUS or smoldering multiple myeloma (SMM) or elevated absolute lymphocyte count on blood count checks leading to MBL identification. Diagnosis of CH requires next-generation sequencing of peripheral blood or bone marrow to identify expansion in somatic genetic alterations in hematopoietic cells. Epidemiologic studies of these precursor conditions show that they are relatively common and increase with age, with prevalence of MGUS of 3%-4% in individuals older than 50 years, 3%-17% in adult populations for MBL, and 10% of individuals older than 50 years for CH. Evaluating the risk of progression to overt disease in an individual with a precursor condition is critical in determining management. Often, the risk of progression is quite low, or the latency period is quite long, and for which observation is the current standard of care among these patients. Various risk stratification systems or calculators have been developed for MGUS/SMM, MBL, and CH to better delineate a patient's risk. There is active clinical investigation regarding the role of early intervention among patients who are at highest risk of progression to active hematologic malignancy.