Bone Marrow Aspirate Can Be Avoided in Low-Risk MGUS Patients

Abstract ³⁹⁹⁷

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasmacell dyscrasia with a high prevalence. Diagnostic criteria include: presence of serum monoclonal component (MC) <30 g/l, <10% clonal plasma cells in the bone marrow (BMPC) and absence of end-organ damage according to CRAB criteria. Define the minimal diagnostic work up of patients with small amount of MC (<1.5 g/dl) at low risk for progression to multiple myeloma (MM) according to Mayo clinic stratification is still a matter of debate. This study assess the risk of missing a MM diagnosis not performing invasive procedures (bone marrow aspirate or biopsy) in presence of small amount MC. After approval by our local ethical committee, we retrospectively reviewed medical records of 2304 patients addressed to our single Hematology department for definition MC of IgG or IgA isotype. Diagnostic work-up included: bone marrow aspirate, skeletal bone survey and laboratory tests (i.e. complete blood count, chemistry screening including calcium and creatinine, serum protein electrophoresis and immunofixation, 24-hour urine electrophoresis for quantification of urinary monoclonal component). Patients were defined as having low-risk MC entity according to IMWG criteria (i.e. <1.5 mg/dl). There were 940 out of 2304 patients (41%) presenting with low-risk MC, among them a not negligible percentage (10%, 93 pts) encountered the criteria for MM after completing the scheduled diagnostic work-up. In detail 36% of them were asymptomatic, the remaining 64% presented at least one of CRAB criteria for active disease (60% had lytic lesions at skeletal survey). When adopting lower cut-off value of MC the criteria for MM were encountered in smaller amount of pts. In detail: 6% (30 out of 499 pts) and 4% (8 out of 206 pts) respectively for cut-off value at 1 or 0.5 g/dl respectively. Univariate analysis found a significant correlation between MC amount and BMPC either in MGUS (p<0.001) and MM patients (p<0.001). The probability of missing a MM diagnosis due to a set of value below a specified cut-off was assessed by means of a ROC curve analysis. The probability of finding a clonal BMPC infiltration ≥10% was of 15.4% keeping the serum MC cut-off value at 1.5 g/dl. The risk of missed MM diagnosis was significantly lower choosing low MC cut-off, with 7.5% and 2.8% risk of missed diagnosis for MC cut-off value of 1 g/dl and 0.5 g/dl respectively. Similar specificity value were found either when selecting patients with none of the CRAB criteria for symptomatic disease or with a IgA isotype. In conclusion our study showed a strict correlation between the amount of serum MC and BMPC infiltration. Excluding cases presenting with any of CRAB symptoms, the risk of missed MM diagnosis is very low (7.5%) in patients with a MC <1 g/dl, confirming the chance to avoid invasive procedures during diagnostic work-up of opportunely selected patients.