Primary Plasma Cell Leukemia: Clinical, Immunophenotypic, DNA Ploidy, and Cytogenetic Characteristics

Abstract

We report on a series of 26 patients diagnosed with primary (de novo) plasma cell (PC) leukemia (PCL) in whom we analyzed the clinicobiologic characteristics of the disease together with the immunophenotype, DNA cell content, proliferative index, and numeric chromosomal aberrations of the neoplastic PC, and compared them with 664 multiple myeloma (MM) patients at diagnosis. The median age, sex ratio, and bone lesion extension were similar, but PCL cases displayed a higher prevalence of clinical stage III, extramedullary involvement, and Bence Jones cases, with fewer IgA cases than for MM patients. In addition, according to several prognostic indicators (β2-microglobulin serum level, proportion of S-phase PCs, proteinuria, calcium serum level, lactate dehydrogenase [LDH] and renal function), the incidence of adverse prognostic factors was significantly higher in PCL versus MM. Immunophenotypic expression was similar for CD38, CD138, CD2, CD3, CD16, CD10, CD13, and CD15, but PCL differed from MM in the expression of CD56, CD9 HLA-DR, CD117, and CD20 antigens. Twenty-two PCL cases were diploid and one was hypodiploid, while most MM cases (57%) showed DNA hyperdiploidy. With the fluorescent in situ hydridization (FISH) technique, 12 of 13 PCL cases displayed the numeric aberrations, −13 (86%), ±1 (57%), +18 (43%), and −X in women (25%), but they lacked several numeric aberrations usually found in MM such as +3, +6, +9, +11, and +15. PCL cases had a lower overall response to therapy than MM cases (38% v 63%, P = .01332). Among PCL patients, a trend for a worse response was observed in cases treated with melphalan and prednisone (MP) versus polychemotherapy. Overall survival was significantly worse in PCL versus MM patients (8 v 36 months,P < .0001), but it was significantly better in PCL patients treated with polychemotherapy versus MP (18 v 3 months,P = .0137). By contrast, MM patients did not show significant differences in overall survival according to the treatment used, MP or polychemotherapy. Ten variables seemed to predict survival in PCL patients, but only the β2-microglobulin level and S-phase PCs retained an independent value in multivariate analysis. In summary, our study illustrates that PCs from PCL display singular phenotypic, DNA cell content, and cytogenetic characteristics that lead to a different disease evolution versus MM.

Plasma cell leukaemia and other aggressive plasma cell malignancies

“…In pPCL, similar to MM, IgG is the most common monoclonal protein. Increased frequency of Bence–Jones proteinuria as an isolated paraproteinemia has also been reported (Garcia‐Sanz et al , 1999). Despite the aggressive nature of PCL there does not seem to be any significant difference in the serum M‐protein levels compared to patients with MM.…”

“…Using conventional metaphase karyotyping, cytogenetic abnormalities have been identified in over 70% of PCL patients (Fonseca et al , 2004). Hypodiploidy and complex karyotypes with multiple numerical and structural abnormalities involving chromosome 1, 13 and 14 have been identified in a significant number of PCL cases (Colovic et al , 2008; Avet‐Loiseau et al , 2001; Garcia‐Sanz et al , 1999). Interestingly, similar distribution of genetic abnormalities have also been demonstrated in non‐Caucasian populations (Xu et al , 2009; Peijing et al , 2009).…”

“…Conversely, PCL patients have lower levels of serum albumin and higher levels of lactate dehydrogenase (LDH), β‐2 microglobulin (≥6 mg/l in more than 65% of patients), serum calcium and serum creatinine, all signifying aggressive disease biology. Most patients with PCL are observed to have an advanced clinical stage (Garcia‐Sanz et al , 1999; Colovic et al , 2008). Additional differentiating features of pPCL include more extensive bone marrow infiltration, often with plasmablastic cytomorphology (Fig 1).…”

“…Akin to the malignant plasma cells from MM or MGUS patients, malignant PCL cells also express CD38 and CD138; however, expression of CD 20 is more prevalent in PCL (Perez‐Andres et al , 2005). Compared to MM, there is reduced expression of CD117, HLA‐DR and CD9 antigens on PCL cells (Garcia‐Sanz et al , 1999). Moreover, absence of CD56 expression (a finding associated with aggressive clinical behaviour in MM patients) is more frequently seen in PCL (Pellat‐Deceunynck et al , 1998; Garcia‐Sanz et al , 1999; Rawstron et al , 1999; Sahara et al , 2002; Colovic et al , 2008).…”

“…Compared to MM, there is reduced expression of CD117, HLA‐DR and CD9 antigens on PCL cells (Garcia‐Sanz et al , 1999). Moreover, absence of CD56 expression (a finding associated with aggressive clinical behaviour in MM patients) is more frequently seen in PCL (Pellat‐Deceunynck et al , 1998; Garcia‐Sanz et al , 1999; Rawstron et al , 1999; Sahara et al , 2002; Colovic et al , 2008). Intriguingly, Perez‐Andres et al (2005) also demonstrated significantly decreased expression of the surface molecules HLA‐1, β‐2M and CD40 on clonal plasma cells from patients with MM and PCL as compared to those from MGUS patients.…”