Symptomatic and Indolent Waldenström’s Macroglobulinemia Display Different Biological and Cytogenetic but Not Immunophenotypic Characteristics.

Waldenström’s Macroglobulinemia (WM) patients are classified in two main subtypes: symptomatic and asymptomatic. In this study we have analyzed the clinical, biological, immunophenotypical and cytogenetic characteristics of 85 WM, including 59 symptomatic WM (SWM) and 26 indolent WM (IWM).

Clinical behaviour of SWM, as expected, was clearly different from that of IWM. Characteristics of the first group included: poor performance status (30%), hyperviscosity syndrome (19%), B symptoms (29%) and neurological symptoms (25%). None of these features were present in IWM.

Regarding biology, most SWM patients (75%) had hemoglobin levels below 12 g/dl while only 8% of IWM showed this feature (p<0.001). Beta2 microglobulin and ESR were significantly higher in SWM than in IWM (3.6 vs 2.3 p=0.008, and 103 vs 62 p<0.001, respectively) and both entities also differed in albumin (3.5 vs 4 p=0.009) and IgM levels (3.4 vs 2.1 p=0.005). Although lymphoid infiltration was higher in SWM, differences did not reach statistical significance (47% vs 34% p=0.06). BM infiltration was predominantly interstitial in IWM (91%) whereas only 44% of SWM had this pattern (p=0.06). Interestingly, SWM patients had higher plasma cell (PC) bone marrow infiltration (2.6% vs 1.5% p=0.006) and a higher proportion of SWM patients showed evidence of mast cells (66% vs 28% p=0.009).

Immunophenotypic characteristics of B cells in SWM and IWM were almost identical, with only slight, but non significant, differences in some markers. The proportion of patients expressing CD27, strong CD24 and bcl-2 were greater in SWM than in IWM (42% vs 28%, 28% vs 17%, and 73% vs 61%, respectively). It should be noted that the frequency of these three markers was even lower in 15 MGUS patients analyzed (18%, 10% and 45% respectively), pointing out to a progressive decrease in expression from SWM to MGUS. Regarding PC, although their number was significantly higher in SWM than in IWM no differences were observed in their immunophenotypic pattern.

Cytogenetic profile was clearly different in SWM as compared to IWM. Thus, 10 out of the 59 SWM (17%) showed chromosomal abnormalities: 8 patients had 6q deletions and 2 patients IgH translocations, while none of the IWM cases displayed 6q deletions. In fact, only 2 out of 26 (8%) IWM showed cytogenetic aberrations: 1 case had IgH translocation and 1 case RB deletion. These results suggest that 6q deletion is associated with a more aggressive course of disease.

In summary, our results show that the different clinical and biological picture of SWM and IWM is associated with a different cytogenetic but not immunophenotypic profile.