Prognostic impact of <scp>CD</scp>5 expression in diffuse large B‐cell lymphoma in patients treated with rituximab‐<scp>EPOCH</scp>

Thakral, Beenu; Medeiros, L. Jeffrey; Desai, Parth; Lin, Pei; Yin, C. Cameron; Tang, Guilin; Khoury, Joseph D.; Hu, Shimin; Xu, Jie; Loghavi, Sanam; Hu, Bei; Oki, Yasuhiro; Li, Shaoying

doi:10.1111/ejh.12847

Cited by 45 publications

(51 citation statements)

References 34 publications

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“…Thakral et al demonstrated that CD5 expression is an independent prognostic factor in DLBCL patients treated with DA-EPOCH-R. 37 Despite the transplantations, some investigators have found that the OS of patients with CD5+ DLBCL could not be improved. [37][38][39] Studies have shown that the overexpression of CD5 in malignant B cells may confer chemo-resistance, upregulate anti-apoptotic signals and change the microenvironment. 40 Further studies are needed to clarify the causes for the poor prognosis of CD5+ DLBCL patients.…”

Section: Discussionmentioning

confidence: 99%

CD5 expression correlates with inferior survival and enhances the negative effect of p53 overexpression in diffuse large B‐cell lymphoma

Zhao

Zhou

et al. 2019

Hematological Oncology

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De novo CD5‐positive diffuse large B‐cell lymphoma (CD5+ DLBCL) is increasingly recognized as a distinct pathologic phenomenon with a specific clinical picture. However, CD5+ DLBCL has not been studied on a large scale in China. In this study, we show that CD5+ DLBCL occurs at a low frequency (9.2%). Comparison of clinical characteristics of CD5+ vs CD5− DLBCL showed that CD5+ DLBCL was more frequently elderly (>60 years) and had B symptoms, high‐performance status, stage III‐IV, an IPI score >2 and bone marrow involvement. Patients with CD5+ DLBCL had tumours with a higher prevalence of BCL‐2 and p53 overexpression than CD5− DLBCL. Patients with CD5+ DLBCL had inferior progression‐free survival (PFS) and overall survival (OS) than did patients with CD5− DLBCL. For CD5+ DLBCL, the patients who were treated with rituximab showed significantly better PFS and OS than those treated without rituximab. However, patients treated with RCHOP showed similar PFS and OS when compared with the group treated with intensive therapy. In addition, patients with p53 and CD5 co‐expression had the worst PFS and OS. In conclusion, CD5+ DLBCL was associated with unfavorable clinicopathologic variables and with inferior survival. CD5+ DLBCL has a high frequency of p53 overexpression, and CD5 augments the negative effect of p53 overexpression in DLBCL.

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Section: Discussionmentioning

confidence: 99%

CD5 expression correlates with inferior survival and enhances the negative effect of p53 overexpression in diffuse large B‐cell lymphoma

Zhao

Zhou

et al. 2019

Hematological Oncology

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“…CNS relapses occurred in 5.8%, without any significant difference according to the administration of intrathecal therapy. Researchers from MD Anderson Cancer Center reported a higher rate of CNS recurrence after DA-EPOCH-R in CD5+ disease (33% versus 16%), which in 50% was associated with extranodal involvement at diagnosis, most commonly in the bone marrow (35%) [47]. CD5 positivity may thus be another marker of disseminated disease with high risk of CNS recurrence, reported as 8–11% in three other series [48–50].…”

Section: Cns Recurrence: Risk Assessment and Prophylaxismentioning

confidence: 99%

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

Ollila

Olszewski

2018

Curr. Treat. Options in Oncol.

111

107

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Diffuse large B cell lymphoma (DLBCL) arises from extranodal organs in about 30% of cases. Its prognosis and risk of recurrence in the central nervous system (CNS) vary according to the primary site of origin. Recent studies begin to clarify these differences using molecular classification. Testicular, breast, and uterine DLBCL (as well as possibly primary cutaneous DLBCL, leg-type) share a high prevalence of the non-germinal center B cell (non-GCB) phenotype and the MYD88/CD79B-mutated (MCD) genotype. These biologic features, which resemble primary CNS lymphoma, may underlie their stage-independent propensity for CNS involvement. Management of these lymphomas should involve CNS prophylaxis, preferably using systemic high-dose methotrexate to prevent intraparenchymal recurrence. Involvement of the kidneys, adrenal glands, ovary, bone marrow, lung, or pleura usually indicates disseminated disease, conferring worse prognosis. Involvement of these sites is often associated with high CNS-International Prognostic Index (IPI), concurrent MYC and BCL2 or BCL6 rearrangements, or intravascular lymphoma-risk factors warranting CNS prophylaxis. In contrast, craniofacial, thyroid, localized bone, or gastric lymphomas have a variable prevalence of the non-GCB phenotype and lack MYD88 mutations. Their outcomes with standard immunochemotherapy are excellent, and the risk of CNS recurrence is low. We recommend individualized consideration of CNS prophylaxis based on the CNS-IPI score and anatomical proximity in cases of epidural, orbital, or skull involvement. Rituximab-containing immunochemotherapy is a standard approach for all extranodal DLBCLs. Surgery is no longer required for any primary site, but routine consolidative radiation therapy is recommended for testicular lymphoma. Radiation therapy also appears to be associated with better progression-free survival in primary bone DLBCL. Future studies should better distinguish primary from secondary sites of extranodal involvement, and investigate the association of newly identified genotypes with the risk of CNS or systemic recurrence.

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“…CD5 is also expressed in 5%‐10% of de novo DLBCL cases, and CD5+ DLBCL has been included as an immunohistochemical subgroup in the fourth edition of the World Health Organization (WHO) classification . Several studies have demonstrated that DLBCL patients with CD5‐positive expression have a poorer overall survival (OS) rate than those without CD5 expression, regardless of the use of rituximab …”

Section: Introductionmentioning

confidence: 99%

“…12 Several studies have demonstrated that DLBCL patients with CD5-positive expression have a poorer overall survival (OS) rate than those without CD5 expression, regardless of the use of rituximab. 23,24 CD43 is a multifunctional type I transmembrane protein that regulates multiple cellular functions, such as cell signal transduction, cell adhesion, activation, proliferation, cell survival, and apoptosis. [25][26][27] CD43 is expressed on the surface of most hematopoietic cells, some lymphomas, and leukemias.…”

mentioning

confidence: 99%

Coexpression of CD5 and CD43 predicts worse prognosis in diffuse large B‐cell lymphoma

Zhong

Zheng

et al. 2018

Cancer Medicine

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Both CD5 and CD43 are expressed on the surface of B lymphocytes of definite phase and associated with the adverse outcome in diffuse large B‐cell lymphoma (DLBCL). However, the relationship between CD5 and CD43 expression and the prognostic value of CD5/CD43 coexpression in DLBCL are unknown. We herein determined the correlation between CD5 and CD43 expression, as separate factors or in combination, with the clinicopathological features and survival of 200 patients with DLBCL receiving standard chemotherapy with or without rituximab. Among these DLBCL patients, CD5 expression, CD43 expression, and CD5/CD43 coexpression were detected in 18 (9%), 57 (27%), and 10 (5%) patients, respectively, and all were positively correlated with advanced age and nongerminal cell type. CD5‐positive and CD43‐positive DLBCL patients had poorer event‐free survival (EFS, P < 0.001) and overall survival (OS, P < 0.001) than CD5‐negative and CD43‐negative patients, respectively. CD5/CD43 coexpression was correlated with a significantly worse prognosis than CD5 or CD43 expression alone. Univariate analysis showed that CD5 expression, CD43 expression, and CD5/CD43 coexpression were all adverse prognostic factors for DLBCL patient survival, and CD5/CD43 coexpression was associated with a greater relative risk for recurrence and death than either CD5 or CD43 expression alone. Multivariate analysis demonstrated that CD5/CD43 coexpression was an independent prognostic factor for EFS (P < 0.001) and OS (P < 0.001) in DLBCL. In conclusion, our data indicate that DLBCL patients with CD5/CD43 coexpression represent a specific subgroup with a significantly worse prognosis than those expressing either marker alone.

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Prognostic impact of CD5 expression in diffuse large B‐cell lymphoma in patients treated with rituximab‐EPOCH

Abstract: R-EPOCH therapy does not seem to impact the known poorer prognosis of patients with de novo CD5+ DLBCL, and CD5 expression was still an independent prognostic factor in R-EPOCH-treated patients with DLBCL.

Cited by 45 publications

References 34 publications

CD5 expression correlates with inferior survival and enhances the negative effect of p53 overexpression in diffuse large B‐cell lymphoma

CD5 expression correlates with inferior survival and enhances the negative effect of p53 overexpression in diffuse large B‐cell lymphoma

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

Coexpression of CD5 and CD43 predicts worse prognosis in diffuse large B‐cell lymphoma

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