Revised diagnostic criteria for plasma cell leukemia: results of a Mayo Clinic study with comparison of outcomes to multiple myeloma

Abstract

The current definition of plasma cell leukemia (PCL)— ≥ 20% circulating plasma cells (CPCs) on peripheral smear and plasma cell count ≥ 2 × 109/L—may be too stringent. We reviewed outcomes of 176 multiple myeloma (MM) patients diagnosed between 1971 and 2016, and who had CPCs detectable at diagnosis, to determine whether a lower threshold could be used to diagnose PCL. Median overall survival (mOS) was 1.1 years (95% CI 0.8–1.4) and was similar between patients with < 5% (n = 54, mOS = 1.4 years [0.7–2.0]), 5–19% (n = 63, mOS = 1.1 years [0.7–1.4]), and ≥ 20% CPCs (n = 59, mOS = 1.1 years [0.7–1.5], p = 0.349). As survival was similar between those with 5–19% and ≥ 20% CPCs, we stratified patients by < 5% (mOS = 1.4 years [0.7–2.0]) and ≥ 5% CPCs (mOS = 1.1 years [0.8–1.4], p = 0.154). Outcomes of those with ≥ 5% CPCs were much poorer when compared with a cohort of MM patients diagnosed between 1971 and 2016, who did not have CPCs at diagnosis (n = 9724, mOS = 4.4 yrs [4.3–4.5], p < 0.001); survival was also lower in patients diagnosed after 2001 with ≥ 5% CPCs (n = 62, mOS = 1.4 years [0.8–2.5]) compared with patients with standard risk (n = 1326, mOS = 7.5 years [7.0–8.7]) and high-risk MM (n = 381, mOS = 4.3 years [3.5–4.9], p < 0.001). We therefore propose that the definition of PCL be revised to patients with ≥ 5% CPCs on peripheral blood smear, who otherwise meet diagnostic criteria for MM.

Enhancing the R‐ISS classification of newly diagnosed multiple myeloma by quantifying circulating clonal plasma cells

“…Thus, the presence of cPCs has suggested a more aggressive disease biology by their independence from their bone marrow microenvironment. This is confirmed clinically by the fact that NDMM patients who meet criteria for having pPCL have the worst survival outcomes, even when compared to NDMM patients with high risk cytogenetics . In addition, this study demonstrated an association of higher levels of cPCs in patients with t(11;14), t(14;16) and deletion 17p, when compared to patients with hyperdiploid disease.…”

“…We retrospectively evaluated all NDMM patients seen at the Mayo Clinic, Rochester from January 2009 to December 2017, who had their peripheral blood samples evaluated by flow cytometry prior to beginning therapy. Any patient who had 5% or more plasma cells and/or an absolute count greater than 0.5 × 10 9 /Llplasma cells on a peripheral blood smear at diagnosis, were excluded for the purposes of this study as they could have had primary plasma cell leukemia (pPCL) by the re‐defined criteria . Approval for this study was obtained from the Mayo Clinic IRB in accordance with the federal regulations and the principles of the Declaration of Helsinki.…”

Rare case of non-producer variant of plasma cell dyscrasias with circulating plasma cells

“…There is no single cytogenetic abnormality that is typical or diagnostic of PCL. Studies have since shown that MM patients with ≥5% to 20% CPCs, as measured on a peripheral smear, have similar outcomes to patients with ≥ 20% CPCs and suggested a lower threshold of CPCs be used to define PCL 19. Given 8% atypical plasmacytoid cells circulating in peripheral blood, loss of FLC secretion, no cytoplasmic immunoglobulin synthesis and without antecedent MM, our patient was diagnosed with non-producer variant of plasma cell dyscrasias with CPCs.…”

“…Among the NSMM cases, there is a subset with loss of FLC secretion by MM clones in which no cytoplasmic immunoglobulin synthesis is detected, and this entity is called NPMM with estimated incidence of 0.15%. MM patients can usually be risk stratified based on cytogenetic abnormalities, lactate dehydrogenase, beta 2 microglobulin, bone marrow plasma cell immunophenotype, monoclonal protein quantity, presence of CPCs, serum FLC ratio, plasma cell proliferative rate and gene expression profiling 12–19…”

Primary plasma cell leukemia: A case report and review of the literature

“…The presence of 5% circulating clonal plasma cells has been suggested to improve detection . This has been echoed by a recent Mayo Clinic study in December 2018 that showed those diagnosed between 1971 and 2016 with > = 5% circulating plasma cells (CPCs) had much poorer survival outcomes compared with those who did not have CPCs on diagnosis . The successful treatment of this patient with VCD and daratumumab may prove an effective induction strategy for similar patients with an aggressive presentation, who are not candidates for AuSCT.…”