T-cell lymphoid aggregates in bone marrow after rituximab therapy for B-cell follicular lymphoma: a marker of therapeutic efficacy?

• Published in: Human pathology 2008-02, Vol.39 (2), p.194-200
• Main Authors: Raynaud, Pierre, MD, Caulet-Maugendre, Sylvie, MD, Foussard, Charles, MD, Salles, Gilles, MD, PhD, Moreau, Anne, MD, Rossi, Jean François, MD, PhD, Patey, Martine, MD, Rousselet, Marie Christine, MD, PhD, Bene, Marie Christine, MD, PhD, Damotte, Diane, MD, Cornillet Lefebvre, Pascale, MD, Martin, Antoine, MD, PhD, Costes, Valérie, MD, PhD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anti-CD20 monoclonal antibodies; Antibodies, Monoclonal; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Agents - therapeutic use; Bcl2; Binding sites; Biological and medical sciences; Bone Marrow; Bone Marrow - pathology; Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 18; DNA, Neoplasm; DNA, Neoplasm - analysis; Female; Follicular lymphoma; Gene Rearrangement; Genes; Hematologic and hematopoietic diseases; Histology; Human health and pathology; Humans; Investigative techniques, diagnostic techniques (general aspects); Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Life Sciences; Lymphoma; Lymphoma, B-Cell; Lymphoma, B-Cell - drug therapy; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - mortality; Lymphoma, B-Cell - pathology; Lymphoma, Follicular; Lymphoma, Follicular - drug therapy; Lymphoma, Follicular - genetics; Lymphoma, Follicular - mortality; Lymphoma, Follicular - pathology; Male; Medical sciences; Middle Aged; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-bcl-2 - genetics; Reverse Transcriptase Polymerase Chain Reaction; Rituximab; Survival Rate; T-cell infiltration; T-Lymphocytes; T-Lymphocytes - pathology; Translocation, Genetic; Treatment Outcome
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2007.05.026

Summary Rituximab, an anti-CD20 monoclonal antibody, is widely used in the treatment of B-cell lymphoma. Some reports have outlined histologic modifications in bone marrow specimens from patients treated with this antibody, notably the presence of CD3+ lymphoid aggregates morphologically mimicking residual lymphoma. To gain insight into the significance of such infiltrates, serial BM trephines obtained in 39 patients with B-cell follicular lymphoma treated by rituximab and enrolled in the GOELAMS-GELA intergroup FL2000 protocol were reexamined. The 39 patients were 22 women and 17 men with a median age of 50 years (range, 29-75 years). All pretreatment bone marrow biopsies showed CD20+ lymphomatous cells. A second biopsy was obtained between 30 and 100 days after the last rituximab injection: 19 (48%) were morphologically diagnosed as negative (no lymphoid infiltrates or only minor lymphoid aggregates) and 20 (51%) as positive because of persistent lymphoid nodules. After immunohistochemical analysis, 13 (33%) cases were reinterpreted as false-positive because of the complete absence of CD20+ cells, with the lymphoid nodules consisting of CD3+ and CD5+ T cells. Most of them also expressed CD4+ , whereas only a few CD8+ cells were present. Among these 13 false-positive cases, 12 were BCL2-IGH polymerase chain reaction–negative in the bone marrow aspirate at the time of biopsy. The 13th case turned out to be negative in the 18th-month bone marrow aspirate. In all of these cases, lymphoid aggregates had disappeared on bone marrow biopsies performed 18 months after treatment. After a mean follow-up of 4.5 years, 9 of 13 patients were in remission as compared with only 2 among the 7 patients with postrituximab persistent CD20+ lymphomatous cells. There was no statistically significant difference between this false-positive group of patients and that with negative postrituximab bone marrow regarding sex, age, medullar involvement pattern before treatment, delay between rituximab treatment, and molecular status. Interestingly, we noted a more favorable outcome (70% versus 52% remission) for the false-positive cases, suggesting that these T-cell reactions could be the hallmark of specific antitumoral immunity after rituximab treatment and should be properly investigated.