The therapeutic effect of rituximab on CD5‐positive and CD5‐negative diffuse large B‐cell lymphoma

Abstract

The prognosis of diffuse large B-cell lymphoma (DLBCL) has improved markedly in recent years of rituximab era. The prognosis of de novo CD5-positive DLBCL is reported to be poor, but the effect of rituximab on this type of lymphoma remains unclear. To investigate the effect of rituximab on CD5-positive DLBCL, we collected DLBCL patients and analysed prognostic factors. A total of 157 patients with DLBCL who were immunophenotyped with flow-cytometry (FCM) and treated with chemotherapy were subjected to analysis. Those treated with radiotherapy alone or with supportive therapy only were not included. Patients diagnosed in 2003 or later were treated with rituximab combined chemotherapy. There were 95 males and 62 females. Their age ranged from 20 to 91 years old, and the median was 65 years. Nineteen patients were diagnosed as having de novo CD5-positive DLBCL. Rituximab was given alongside chemotherapy in 85 patients. Of these, 11 were positive for CD5 and 74 were negative. The addition of rituximab improved the overall survival (OS) of DLBCL patients (2-year OS: 82% vs. 70%, p = 0.01). For CD5-negative DLBCL, patients treated with rituximab showed 2-year OS of 84%, which was significantly better than those treated without rituximab (70%, p = 0.008). However, for CD5-positive DLBCL, the prognosis was not statistically different between the patients treated with and without rituximab (59% vs. 50%, p = 0.72). Although rituximab improved the prognosis of DLBCL, such improvement was restricted to the CD5-negative group. Further investigation is required to improve the prognosis of patients with CD5-positive DLBCL.

Multiparameter analysis of homogeneously R-CHOP-treated diffuse large B cell lymphomas identifies CD5 and FOXP1 as relevant prognostic biomarkers: report of the prospective SAKK 38/07 study

“…CD5-positive DLBCL are typically ABC [42, 48], show recurrent gains of 16p and losses of 1p and of 9q21 [36, 49], the latter being involved in chemoresistance [37], and display downregulation of extracellular matrix-related genes and upregulation of neurological function-related genes [48]. Addition of rituximab to CHOP improved the survival of CD5-positive DLBCL patients [50]; however, similarly to our results, the outcome of these patients is still significantly poorer compared to CD5-negative DLBCL patients [51], and the rate of CNS involvement seems not to be lowered by rituximab [52]. A recent very large retrospective report on 879 R-CHOP-treated DLBCL cases convincingly showed CD5 to be an IPI (and bcl2 and pSTAT3)-independent prognosticator in DLBCL as well [53] and pointed out distinct clinico-pathological peculiarities of such patients such as increased age, bone marrow spread, poor performance status, and B symptoms.…”

Clinical and biological significance ofde novoCD5+ diffuse large B-cell lymphoma in Western countries

“…Bone marrow (BM) involvement (28%) and central nervous system (CNS) relapse (12.7%) are increased in CD5 + DLBCL patients [14, 16, 20]. However, in one study CD5 expression status did not correlate with prognosis by univariate or multivariate analysis, either in all patients or in rituximab-treated patients [18]. The effect of adding rituximab to CHOP on survival of CD5 + DLBCL patients also has been inconsistent in different studies [18-20].…”

“…However, in one study CD5 expression status did not correlate with prognosis by univariate or multivariate analysis, either in all patients or in rituximab-treated patients [18]. The effect of adding rituximab to CHOP on survival of CD5 + DLBCL patients also has been inconsistent in different studies [18-20]. In Western countries, a few cases of de novo CD5 + DLBCL have been reported [21, 22], and a morphologic and immunophenotypic study of 13 cases of de novo CD5 + DLBCL showed heterogeneous features [23].…”

B-cell lymphomas with features intermediate between distinct pathologic entities. From pathogenesis to pathology

“…Five percent to 10% of DLBCL are CD5-positive. This marker identifies a subset of ABC-type DLBCL characterized by advanced stage of disease at diagnosis, aggressive clinical course, and resistance to rituximab therapy [45]. BCL2 positivity (a condition associated with poor prognosis) and lack of CD10 are more frequently observed within CD5 + DLBCL.…”