Lowering the Diagnostic Threshold in Secondary Plasma Cell Leukemia? Comparison With Primary Cases and Implications...

In 2021, the International Myeloma Working Group lowered the threshold to establish the diagnosis of primary plasma cell leukemia (pPCL) from ≥20% to ≥5% circulating plasma cells (CPCs) as assessed by morphologic evaluation (ME). However, the threshold for defining secondary PCL (sPCL) remains unclear. We retrospectively studied the clinicopathological features of 52 PCL patients, 30 pPCL and 22 sPCL, with ≥5% CPCs determined by either ME or flow cytometry immunophenotyping (FCI). FCI often revealed a higher percentage of CPCs than ME, likely due to difficulties in identifying morphologically abnormal plasma cells with certainty, and this discordance was statistically significant in sPCL patients. pPCL and sPCL both exhibited leukocytosis, thrombocytopenia, infrequent CD56 expression, high bone marrow tumor burden, and complex karyotypes. MYC rearrangement was observed only in sPCL cases. Paired cytogenetic data before and after leukemic transformation were available in a small subset of sPCL patients (8/22). Compared with the prior myeloma, sPCL more frequently harbored a complex karyotype, hypodiploidy, and additional cytogenetic abnormalities, most commonly gain of chromosome 1q. Using 5% CPCs as the diagnostic threshold, patients with sPCL had significantly poorer outcomes than patients with pPCL (P < .0001). Furthermore, the outcomes of sPCL patients with 5% to 19% CPCs were similarly poor as those patients with ≥20% CPCs (P = .4781), highlighting the need to recognize patients with ≥5% CPCs promptly. FCI appears to be a more sensitive method for this purpose in most cases. Using FCI, further studies are needed to determine whether a diagnostic threshold of 5% or lower may be used to establish the diagnosis of sPCL.