Primary testicular diffuse large B-cell lymphoma displays distinct clinical and biological features for treatment failure in rituximab era

A report from the International PTL Consortium

L. Deng, Z. Y. Xu-Monette, S. Loghavi, G. C. Manyam, Y. Xia, C. Visco, J. Huh, L. Zhang, Q. Zhai, Y. Wang, L. Qiu, K. Dybkær, A. Chiu, A. M. Perry, Shanxiang Zhang, A. Tzankov, H. Rao, J. Abramson, A. R. Sohani, M. Xu & 12 others E. D. Hsi, J. Zhu, M. Ponzoni, S. Wang, Ling Li, M. Zhang, A. J.M. Ferreri, B. M. Parsons, Y. Li, M. A. Piris, L. J. Medeiros, K. H. Young

Research output: Contribution to journalArticle

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Abstract

Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a unique subtype of DLBCL. The impact of rituximab on survival and patterns of treatment failure in PT-DLBCL patient remain controversial. We analyzed the clinical and biological feature of 280 PT-DLBCL cases, 64% of which were treated with rituximab-containing regimens. Although most (95%) patients achieved complete remission, a continuous risk of relapse was observed. Rituximab significantly reduced the cumulative risk of relapse (P=0.022) and improved both progression-free survival (PFS, P=0.012) and overall survival (OS, P=0.027) of PT-DLBCL patients (5-year PFS, 56% vs 36%; 5-year OS, 68% vs 48%). Central nervous system and contralateral testis were the most common sites of relapse, but other extranodal and nodal sites of relapse were also observed. Most cases of PT-DLBCL had a non-germinal center B-cell like (84%) immunophenotype and an activated B-cell like (86%) gene expression profile (GEP) subtype. The distinctive GEP signature of primary testicular lymphoma was relevant to tumor cell proliferation, dysregulated expression of adhesion molecules and immune response, likely accounting for the poor outcome. Accordingly, forkhead box P1 transcription factor (FOXP1) and T-cell leukemia/lymphoma 1 (TCL1) oncogenic activation were confirmed and predicted a significant trend of poor survival. This study provides valuable observations for better understanding of both clinical and biological features in PT-DLBCL patients.

Original languageEnglish (US)
Pages (from-to)361-372
Number of pages12
JournalLeukemia
Volume30
Issue number2
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Treatment Failure
Transcriptome
Recurrence
Survival
B-Lymphocytes
Forkhead Transcription Factors
T-Cell Leukemia
T-Cell Lymphoma
Disease-Free Survival
Rituximab
Testis
Lymphoma
Central Nervous System
Cell Proliferation
Neoplasms

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Primary testicular diffuse large B-cell lymphoma displays distinct clinical and biological features for treatment failure in rituximab era : A report from the International PTL Consortium. / Deng, L.; Xu-Monette, Z. Y.; Loghavi, S.; Manyam, G. C.; Xia, Y.; Visco, C.; Huh, J.; Zhang, L.; Zhai, Q.; Wang, Y.; Qiu, L.; Dybkær, K.; Chiu, A.; Perry, A. M.; Zhang, Shanxiang; Tzankov, A.; Rao, H.; Abramson, J.; Sohani, A. R.; Xu, M.; Hsi, E. D.; Zhu, J.; Ponzoni, M.; Wang, S.; Li, Ling; Zhang, M.; Ferreri, A. J.M.; Parsons, B. M.; Li, Y.; Piris, M. A.; Medeiros, L. J.; Young, K. H.

In: Leukemia, Vol. 30, No. 2, 01.02.2016, p. 361-372.

Research output: Contribution to journalArticle

Deng, L, Xu-Monette, ZY, Loghavi, S, Manyam, GC, Xia, Y, Visco, C, Huh, J, Zhang, L, Zhai, Q, Wang, Y, Qiu, L, Dybkær, K, Chiu, A, Perry, AM, Zhang, S, Tzankov, A, Rao, H, Abramson, J, Sohani, AR, Xu, M, Hsi, ED, Zhu, J, Ponzoni, M, Wang, S, Li, L, Zhang, M, Ferreri, AJM, Parsons, BM, Li, Y, Piris, MA, Medeiros, LJ & Young, KH 2016, 'Primary testicular diffuse large B-cell lymphoma displays distinct clinical and biological features for treatment failure in rituximab era: A report from the International PTL Consortium', Leukemia, vol. 30, no. 2, pp. 361-372. https://doi.org/10.1038/leu.2015.237
Deng, L. ; Xu-Monette, Z. Y. ; Loghavi, S. ; Manyam, G. C. ; Xia, Y. ; Visco, C. ; Huh, J. ; Zhang, L. ; Zhai, Q. ; Wang, Y. ; Qiu, L. ; Dybkær, K. ; Chiu, A. ; Perry, A. M. ; Zhang, Shanxiang ; Tzankov, A. ; Rao, H. ; Abramson, J. ; Sohani, A. R. ; Xu, M. ; Hsi, E. D. ; Zhu, J. ; Ponzoni, M. ; Wang, S. ; Li, Ling ; Zhang, M. ; Ferreri, A. J.M. ; Parsons, B. M. ; Li, Y. ; Piris, M. A. ; Medeiros, L. J. ; Young, K. H. / Primary testicular diffuse large B-cell lymphoma displays distinct clinical and biological features for treatment failure in rituximab era : A report from the International PTL Consortium. In: Leukemia. 2016 ; Vol. 30, No. 2. pp. 361-372.
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title = "Primary testicular diffuse large B-cell lymphoma displays distinct clinical and biological features for treatment failure in rituximab era: A report from the International PTL Consortium",
abstract = "Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a unique subtype of DLBCL. The impact of rituximab on survival and patterns of treatment failure in PT-DLBCL patient remain controversial. We analyzed the clinical and biological feature of 280 PT-DLBCL cases, 64{\%} of which were treated with rituximab-containing regimens. Although most (95{\%}) patients achieved complete remission, a continuous risk of relapse was observed. Rituximab significantly reduced the cumulative risk of relapse (P=0.022) and improved both progression-free survival (PFS, P=0.012) and overall survival (OS, P=0.027) of PT-DLBCL patients (5-year PFS, 56{\%} vs 36{\%}; 5-year OS, 68{\%} vs 48{\%}). Central nervous system and contralateral testis were the most common sites of relapse, but other extranodal and nodal sites of relapse were also observed. Most cases of PT-DLBCL had a non-germinal center B-cell like (84{\%}) immunophenotype and an activated B-cell like (86{\%}) gene expression profile (GEP) subtype. The distinctive GEP signature of primary testicular lymphoma was relevant to tumor cell proliferation, dysregulated expression of adhesion molecules and immune response, likely accounting for the poor outcome. Accordingly, forkhead box P1 transcription factor (FOXP1) and T-cell leukemia/lymphoma 1 (TCL1) oncogenic activation were confirmed and predicted a significant trend of poor survival. This study provides valuable observations for better understanding of both clinical and biological features in PT-DLBCL patients.",
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T2 - A report from the International PTL Consortium

AU - Deng, L.

AU - Xu-Monette, Z. Y.

AU - Loghavi, S.

AU - Manyam, G. C.

AU - Xia, Y.

AU - Visco, C.

AU - Huh, J.

AU - Zhang, L.

AU - Zhai, Q.

AU - Wang, Y.

AU - Qiu, L.

AU - Dybkær, K.

AU - Chiu, A.

AU - Perry, A. M.

AU - Zhang, Shanxiang

AU - Tzankov, A.

AU - Rao, H.

AU - Abramson, J.

AU - Sohani, A. R.

AU - Xu, M.

AU - Hsi, E. D.

AU - Zhu, J.

AU - Ponzoni, M.

AU - Wang, S.

AU - Li, Ling

AU - Zhang, M.

AU - Ferreri, A. J.M.

AU - Parsons, B. M.

AU - Li, Y.

AU - Piris, M. A.

AU - Medeiros, L. J.

AU - Young, K. H.

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