IgG and IgA hypogammaglobulinemia is pervasive in Waldenstrom's macroglobulinemia (WM) and persists regardless of response or type of therapeutic intervention

Abstract

8042 Background: IgG and IgA hypogammaglobulinemia (HG) is a commonly observed in patients with WM and has often been attributed to the extensive infiltration of lymphoplasmacytic cells in the bone marrow (BM). Methods: In this retrospective study we analyzed immunoglobulin and BM infiltration levels from 196 previously untreated patients at their first visit to our clinic who met the clinical and pathological criteria for WM. In addition, we also serially evaluated 65 WM patients who received various therapies for changes in IgA and IgG. All lab values and biopsies used were conducted at our clinic at the Dana-Farber Cancer Institute to insure consistency. Pre-therapy, end of therapy, and best Ig response post therapy were evaluated and patients were followed up to the point of their next treatment regimen. Results: Of the 197 previously untreated patients, 117 (59.7%) demonstrated abnormally low levels of IgG (<700 mg/dl), whereas 131 (66.8%) had abnormally low levels of IgA (<70 mg/dl), and 102 (52.0%) had abnormally low levels of both IgG and IgA. Median value for IgM was 2820 mg/dl (Range 179 - 12400), for IgG 623 mg/dl (Range 127–2770), for IgA 48.5 mg.dl (range 7 - 509), and for the 94 patients for whom BM biopsies were available, the median intratrabecular space involvement was 37.5% (range 5 - 95). No correlation was found between BM involvement and any Ig level. Results from each of the trials is summarized in the table below. Median follow up was 455 days. No correlation between degree of response and Ig recovery was observed. No Ig level that started abnormally low was ever restored to normal levels in this study despite the fact that some recovery is noted in the non-rituximab based trials. Conclusions: These studies indicate that there is no relationship between BM involvement HG in WM. Moreover, therapeutic intervention does not restore IgG or IgA levels indicating a possible constitutive Ig dysregulation problem in patients with WM. No significant financial relationships to disclose. [Table: see text]