Bone Marrow Mast Cells Are Significantly Increased in Patients with Waldenstrom’s Macroglobulinemia, and Their Number Following Therapeutic Intervention Is Dependent on Extent of Response.

INTRODUCTION: In previous studies, we demonstrated that mast cells (MCs) may support the growth and survival of lymphoplasmacytic cells (LPC) in WM patients through expression of several ligands including CD40L, B-LYS, PDGFa and VEGF. While increased numbers of MC, as well as their association with LPC in the bone marrow (BM) of patients with WM has previously been reported, their enumeration before and following therapeutic intervention remains to be clarified.

METHODOLOGY: We therefore enumerated MC using tryptase staining in whole sections of BM trephine biopsies before and after therapy for 19 patients (median age 59; range 49–85 years) with the consensus panel diagnosis of WM who received rituximab (n=4), rituximab plus fludarabine (n=14) or bortezomib (n=1). Biopsies from 7 non-WM, age matched patients with normal trilineage myelopoiesis and who demonstrated no evidence of disease were used as controls.

RESULTS: At baseline, an increased number of BMMC was observed for WM patients (median 49/mm²; range 0.4–149.5/mm²) versus control patients (median 14/mm², range 3.8–31.4/mm²); p=0.003. Among non-responding patients, the median number of BMMC rose from 42.76/mm² (range 23.3–134.6/mm²) to 72.59/mm² (range 59.1–77.9/mm², n=4), while it remained stable for minor responders 14.9/mm² (range 0.4–26.6/mm²) to 15.8/mm² (range 11.9–44.8/mm², n=3), and decreased for major responders (CR and PR) from 56.6/mm² (range 7.1–149.5/mm²) to 34.13/mm² (range 3.3–110.9/mm², n=12).

CONCLUSION: These preliminary studies demonstrate that BMMC are significantly increased in patients with WM, and their number following therapeutic intervention is dependent on extent of response.