The Secretion of Paraprotein Is Associated with Bone Marrow Involvement in Patients with Diffuse Large B-Cell Lymphoma

Background: Except multiple myeloma secretion of monoclonal paraprotein may be associated with several malignant conditions (lymphomas), they are produced by abnormally expanded single clone of plasma cells in an amount that can be detected in serum, urine, or rarely in other body fluids. A secretion of monoclonal paraprotein related to the neoplastic clone, was detected in more than 10% of newly diagnosed diffuse large B-cell lymphoma (DLBCL). M-protein in DLBCL might be easily missed, the rarity of associated clinical signs and the rapid fading during treatment. This group of DLBCL showed homogeneous morphologic and immunohistochemical features consistent with the non GCB-type. FISH analysis was negative for c-MYC gene rearrangements. M-protein in DLBCL patients, might be related to a very poor non GCB-type subset who should be given upfront intensified therapies [ASH 2012, abstract 2659]. The role and biological relevance of monoclonal paraprotein in diffuse large B-cell lymphoma is unknown.

Aims: to compare the clinical and biological features of DLBCL patients with and without secretion of paraprotein.

Patients and methods: We included in the study 86 high-risk DLBCL patients, diagnosed between July 2007 and September 2014. All patients were treated with intensified therapy (mNHL-BFM-90 or R-DA-EPOCH/R-HMA). 14 cases (16%) with monoclonal secretion paraprotein was identified. The Hans algorithm was used in order to classify cases of DLBCL as GCB-type and non GCB-type at the moment of diagnosis. Bone marrow involvement was identified by histological and B-cell clonality study.

Results: We detected different types of protein in DLBCL: Mk (in 5 patients), Bence-Jones k (3 pts), Gk (2 pts), Ak (1 pts), Mλ (2 pts), Bence-Jones λ (2 pts), Gλ (2 pts), Aλ (1 pts). Four cases have shown 2 different clones simultaneously. Secretion ranged from trace to 27,1 g/l. 12 of 14 cases with monoclonal secretion were classified as non-GCB-type DLBCL. Characteristic of patients with monoclonal secretion were: stage III-IV; ECOG 2-3; median age 57 years (28-71); age ≥60y/<60y 43%/47%; M/F 71%/29%; IPI: 21% high-intermediate and 79% high risk; 93% with bone marrow involvement. We grouped the patients depending of bone marrow involvement, and according to the long-rank analysis only detection of monoclonal secretion of immunoglobulins was associated with bone marrow involvement in patients with diffuse large B-cell lymphoma (Table 1).

Conclusions: Our study has shown that monoclonal secretion of paraprotein was associated with bone marrow involvement in patients with diffuse large B-cell lymphoma. Detection of secretion of paraprotein could help to suspect the cases with bone marrow involvement before the results of histology and when histology not informative. Diffuse large B-cell lymphoma with bone marrow involvement is characterized by aggressive course and poor response to standard chemotherapy.