Lymphoplasmacytic lymphoma immunocytoma: Towards a disease-targeted treatment?

Lymphoplasmacytic-lymphoplasmacytoid lymphoma. (LPL) / Waldenstrom's macrog lobulinemia (WM) or immunocytoma (IMC) consists of diffuse proliferation of small mature B lymphocytes, plasmacytoid lymphocytes, and plasma-cells. Th e nosographic definition includes the lack of histological, immunophenotypi c, cytogenetic, and molecular markers considered specific of other types of lymphoma. The cells show surface Ig (usually IgM), B-cell-associated antig ens and display the CD5-, CD23- and CD10- phenotype, which allows for diffe rential diagnosis from B-CLL and mantle cell lymphoma. t(9;14)(p13;q32) chr omosomal translocation has been found in 50% of all LPL cases. The cytogene tic rearrangement juxtaposes the PAX-5 gene, which encodes for an essential transcription factor for B-cell proliferation and differention, to the Ig heavy chain gene. The combination of chlorambucil and prednisone holds as t he standard treatment and seems to guarantee good control of the disease in most patients. Similar therapeutic results have been described with the co mbination of cyclophosphamide, vincristine, prednisone with (CHOP) or witho ut doxorubicin (CVP), or with a combination of other alkylating agents and prednisone. Nucleoside analogues, alone or in combination with alkylating a gents and anthracyclines, provide good salvage therapy for IMC and being in creasingly employed as first line therapy. In a multicentric European trial Foran et al. administered the chimeric anti-CD20-monoclonal antibody (Ritu ximab) to 28 patients with previously treated IMC. Seven out of 25 evaluabl e patients (28%) achieved a partial response. Byrd et al. examined the outc ome of 7 previously treated WM patients who received weekly infusions of ri tuximab (375 mg/m(2)). Therapy was well tolerated by all patients, and ther e was no decrease in cellular immune function, or significant infectious mo rbidity. Partial responses were noted in three of these patients, including two with fludarabine-refractory disease. These data suggest that rituximab exerts clinical activity on heavily pre-treated patients with WM. Furtherm ore, Weide et al, first reported that WM-associated polyneuropathy can be t reated effectively with a combination of chemotherapy and the anti-CD20 mon oclonal antibody rituximab. Most published trials exploring the efficacy of high dose treatment as salvage therapy for relapsed or refractory low grad e non Hodgkin's lymphoma have included prevalently follicular or lymphocyti c lymphomas. In selected high risk patients radioimmunotherapy with autolog ous stem-cell rescue, and myeloablative therapy followed either by autologo us stem cell transplantation (SCT) or allogeneic SCT might represent an alt ernative strategy.