Long-term plasmapheresis in conjunction with thalidomide and dexamethasone for the treatment of cutaneous ulcers and neovascular glaucoma in recalcitrant type I cryoglobulinemia.

IMPORTANCE: Cryoglobulins are cold-precipitating immunoglobulins that occur secondary to lymphoproliferative disorders, chronic viral infections, and autoimmune disorders. The treatment of cryoglobulinemia should target the underlying disorder; however, such an approach may be difficult, and therapeutic options remain limited for type I cryoglobulinemia. OBSERVATIONS: We report a case of recalcitrant type I cryoglobulinemia treated successfully with long-term plasmapheresis in conjunction with thalidomide and dexamethasone. A woman in her 50s with cryoglobulinemia and bilateral lower extremity ulcers of 1 year's duration developed acute angle-closure glaucoma following the appearance of new macules on her upper extremities. An initial short course of 5 plasmapheresis treatments improved the patient's cutaneous lesions as well as the glaucoma. Three weekly doses of rituximab were not associated with any evidence of clinical improvement, so thalidomide and dexamethasone were administered as replacement therapy. Because of the increasing pain and persistence of the woman's ulcers, intensive plasmapheresis was resumed and continued 3 to 4 times per week for approximately 4 months, after which a slow tapering regimen was initiated. This therapy was associated with progressive, rapid healing of the ulcers, stabilization of the skin lesions, and control of the patient's intraocular pressure. CONCLUSIONS AND RELEVANCE: The long-term use of plasmapheresis may be a well-tolerated treatment option for therapeutically challenging cases of cryoglobulinemia.

CD52 is expressed on human mast cells and is a potential therapeutic target in Waldenstrom's Macroglobulinemia and mast cell disorders.

BACKGROUND: Alemtuzumab is a monoclonal antibody used in the treatment of CD52-expressing B-cell malignancies, including Waldenstrom's macroglobulinemia (WM). Recent studies demonstrate high levels of alemtuzumab activity in relapsed/refractory disease. One potential target of alemtuzumab is bone marrow mast cells (BMMCs), which provide growth and survival signaling for WM lymphoplasmacytic cells. PATIENTS AND METHODS: We therefore examined BMMCs (FceRI+, CD117+) from WM and other mast cell (MC) disorders for expression of CD52. RESULTS: We identified cell surface antigen expression by multicolor flow cytometric analysis and found CD52 expressed on human mast-derived cell line-1 (HMC-1) and LAD2 MC lines, on BMMC from 13 of 15 patients with WM, and on BMMCs from 4 of 4 patients with systemic mastocytosis (SM). None of 4 healthy donors expressed CD52. Reverse-transcriptase polymerase chain reaction analysis confirmed CD52 expression in the HMC-1 and LAD2 MC lines, in BMMCs from 14 of 15 patients with WM, and 3 of 3 patients with SM. CD52 transcripts were also detected in BMMCs from 6 of 6 healthy donors, despite the absence of CD52 cell surface expression. Importantly, we observed high levels of alemtuzumab-mediated, antibody-dependent, cell-mediated cytotoxicity against LAD2 MCs and BMMCs from patients with WM and SM. CONCLUSION: These studies demonstrate that CD52 is widely expressed on human MCs and WM bone marrow lymphoplasmacytic cells and provide the preclinical rationale for the use of alemtuzumab in the treatment of WM and possibly other MC-related disorders.