The Cytogenetic Profile of Primary and Secondary Plasma Cell Leukemia: Etiopathogenetic Perspectives, Prognostic Impact and Clinical Relevance to Newly Diagnosed Multiple Myeloma with Differential Circulating Clonal Plasma Cells.

Stefanos I Papadhimitriou,Meletios-Athanasios Dimopoulos,Efstathios Kastritis,Konstantinos Liapis,Ioannis V Kostopoulos,Theodoros Marinakis,Ourania E Tsitsilonis,Dimitrios Pavlidis,Evangelos Terpos

doi:10.3390/biomedicines10020209

Stefanos I Papadhimitriou, Meletios-Athanasios Dimopoulos + Show 7 more

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https://doi.org/10.3390/biomedicines10020209

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Plasma cell leukemia (PCL) is a rare and aggressive plasma cell dyscrasia that may appear as de-novo leukemia (pPCL) or on the basis of a pre-existing multiple myeloma (MM), called secondary plasma cell leukemia (sPCL). In this prospective study, we have applied a broad panel of FISH probes in 965 newly diagnosed MM (NDMM) and 44 PCL cases of both types to reveal the particular cytogenetic differences among the three plasma cell dyscrasias. In order to evaluate the frequency and patterns of clonal evolution, the same FISH panel was applied both at diagnosis and at the time of first relapse for 81 relapsed MM patients and both at MM diagnosis and during sPCL transformation for the 19 sPCL cases described here. pPCL was characterized by frequent MYC translocations and t(11;14) with a 11q13 breakpoint centered on the MYEOV gene, not commonly seen in MM. sPCL had a higher number of FISH abnormalities and was strongly associated with the presence of del(17p13), either acquired at the initial MM stage or as a newly acquired lesion upon leukemogenesis in the context of the apparent clonal evolution observed in sPCL. In clinical terms, sPCL showed a shorter overall survival than pPCL with either standard or high-risk (t(4;14) and/or t(14;16) and/or del(17p13) and/or ≥3 concomitant aberrations) abnormalities (median 5 months vs. 21 and 11 months respectively, p < 0.001), suggesting a prognostic stratification based on cytogenetic background. These observations proved relevant in the NDMM setting, where higher levels of circulating plasma cells (CPCs) were strongly associated with high-risk cytogenetics (median frequency of CPCs: 0.11% of peripheral blood nucleated cells for high-risk vs. 0.007% for standard-risk NDMM, p < 0.0001). Most importantly, the combined evaluation of CPCs (higher or lower than a cut-off of 0.03%), together with patients’ cytogenetic status, could be used for an improved prognostic stratification of NDMM patients.

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Plasma cell leukemias (PCL) are a rare form of lymphoid malignancies accounting for about 0.3% of leukemias and 0.5–4% of plasma-cell dyscrasias (PCD), with an overall incidence of 0.04 new cases/100.000 individuals per year in Europe [1,2,3]
It was proposed that PCL should be defined by the presence of >5% circulating plasma cells based on findings showing the same adverse outcomes as those with the traditional 20% cut-off definition [8]
In most cases (50–70%), PCL appears as a de-novo leukemia, called primary PCL, but it can arise on the basis of a pre-existing, and usually end-stage, multiple myeloma (MM), called secondary PCL

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Plasma cell leukemias (PCL) are a rare form of lymphoid malignancies accounting for about 0.3% of leukemias and 0.5–4% of plasma-cell dyscrasias (PCD), with an overall incidence of 0.04 new cases/100.000 individuals per year in Europe [1,2,3]. The diagnosis of PCL has been based on Kyle’s criteria, referring to the presence of >20% plasma cells in the peripheral blood (PB) and/or a circulating plasma cell count of >2 × 109 /L [4]. It was proposed that PCL should be defined by the presence of >5% circulating plasma cells based on findings showing the same adverse outcomes as those with the traditional 20% cut-off definition [8]. In most cases (50–70%), PCL appears as a de-novo leukemia, called primary PCL (pPCL), but it can arise on the basis of a pre-existing, and usually end-stage, multiple myeloma (MM), called secondary PCL (sPCL).

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