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

doi:10.3390/biomedicines10020209

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

Biomedicines. 2022 Jan 19;10(2):209. doi: 10.3390/biomedicines10020209.

Authors

Stefanos I Papadhimitriou¹, Evangelos Terpos², Konstantinos Liapis³, Dimitrios Pavlidis¹, Theodoros Marinakis⁴, Efstathios Kastritis², Meletios-Athanasios Dimopoulos², Ourania E Tsitsilonis⁵, Ioannis V Kostopoulos^{1

5}

Affiliations

¹ Department of Laboratory Hematology, Athens Regional General Hospital "Georgios Gennimatas", 11527 Athens, Greece.
² Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.
³ Department of Haematology, University Hospital of Alexandroupolis, Democritus University of Thrace Medical School, 68100 Alexandroupolis, Greece.
⁴ Department of Clinical Hematology, Athens Regional General Hospital "Georgios Gennimatas", 11527 Athens, Greece.
⁵ Department of Biology, School of Sciences, National and Kapodistrian University of Athens, Panepistimiopolis, Ilissia, 15784 Athens, Greece.

Abstract

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.

Keywords: FISH; circulating plasma cells; clonal evolution; cytogenetics; multiple myeloma; primary plasma cell leukemia; secondary plasma cell leukemia.