Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone

Tina Marie Green, Ken H. Young, Carlo Visco, Zijun Y. Xu-Monette, Attilio Orazi, Ronald S. Go, Ole Nielsen, Ole V. Gadeberg, Torben Mourits-Andersen, Mikael Frederiksen, Lars Møller Pedersen, Michael Boe Møller

Research output: Contribution to journalArticle

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Abstract

Purpose: Approximately 5% of diffuse large B-cell lymphomas (DLBCLs) are double-hit lymphomas (DHLs) with translocations of both MYC and BCL2. DHLs are characterized by poor outcome. We tested whether DLBCLs with high expression of MYC protein and BCL2 protein share the clinical features and poor prognosis of DHLs. Patients and Methods: Paraffin-embedded lymphoma samples from 193 patients with de novo DLBCL who were uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were studied using immunohistochemistry for MYC, BCL2, CD10, BCL6, and MUM1/interferon regulatory factor 4, and fluorescent in situ hybridization (FISH) for MYC and BCL2. Results: FISH analysis identified DHL in 6% of patients, who showed the expected poor overall survival (OS; P = .002). On the basis of immunohistochemical MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group, defined by high expression of both MYC and BCL2 protein, comprised 29% of the patients. DHS 2 was significantly associated with lower complete response rate (P = .004), shorter OS (P < .001), and shorter progression-free survival (PFS; P < .001). The highly significant correlation with OS and PFS was maintained in multivariate models that controlled for the International Prognostic Index and the cell-of-origin subtype (OS, P < .001; PFS, P < .001). DHS was validated in an independent cohort of 116 patients who were treated with R-CHOP. Conclusion: The immunohistochemical DHS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP.

Original languageEnglish (US)
Pages (from-to)3460-3467
Number of pages8
JournalJournal of Clinical Oncology
Volume30
Issue number28
DOIs
StatePublished - Oct 1 2012
Externally publishedYes

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Lymphoma, Large B-Cell, Diffuse
Vincristine
Prednisone
Doxorubicin
Cyclophosphamide
Lymphoma
Proto-Oncogene Proteins c-bcl-2
Fluorescence In Situ Hybridization
Rituximab
Paraffin
Disease-Free Survival
Immunohistochemistry
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. / Green, Tina Marie; Young, Ken H.; Visco, Carlo; Xu-Monette, Zijun Y.; Orazi, Attilio; Go, Ronald S.; Nielsen, Ole; Gadeberg, Ole V.; Mourits-Andersen, Torben; Frederiksen, Mikael; Pedersen, Lars Møller; Møller, Michael Boe.

In: Journal of Clinical Oncology, Vol. 30, No. 28, 01.10.2012, p. 3460-3467.

Research output: Contribution to journalArticle

Green, TM, Young, KH, Visco, C, Xu-Monette, ZY, Orazi, A, Go, RS, Nielsen, O, Gadeberg, OV, Mourits-Andersen, T, Frederiksen, M, Pedersen, LM & Møller, MB 2012, 'Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone', Journal of Clinical Oncology, vol. 30, no. 28, pp. 3460-3467. https://doi.org/10.1200/JCO.2011.41.4342
Green, Tina Marie ; Young, Ken H. ; Visco, Carlo ; Xu-Monette, Zijun Y. ; Orazi, Attilio ; Go, Ronald S. ; Nielsen, Ole ; Gadeberg, Ole V. ; Mourits-Andersen, Torben ; Frederiksen, Mikael ; Pedersen, Lars Møller ; Møller, Michael Boe. / Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 28. pp. 3460-3467.
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title = "Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone",
abstract = "Purpose: Approximately 5{\%} of diffuse large B-cell lymphomas (DLBCLs) are double-hit lymphomas (DHLs) with translocations of both MYC and BCL2. DHLs are characterized by poor outcome. We tested whether DLBCLs with high expression of MYC protein and BCL2 protein share the clinical features and poor prognosis of DHLs. Patients and Methods: Paraffin-embedded lymphoma samples from 193 patients with de novo DLBCL who were uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were studied using immunohistochemistry for MYC, BCL2, CD10, BCL6, and MUM1/interferon regulatory factor 4, and fluorescent in situ hybridization (FISH) for MYC and BCL2. Results: FISH analysis identified DHL in 6{\%} of patients, who showed the expected poor overall survival (OS; P = .002). On the basis of immunohistochemical MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group, defined by high expression of both MYC and BCL2 protein, comprised 29{\%} of the patients. DHS 2 was significantly associated with lower complete response rate (P = .004), shorter OS (P < .001), and shorter progression-free survival (PFS; P < .001). The highly significant correlation with OS and PFS was maintained in multivariate models that controlled for the International Prognostic Index and the cell-of-origin subtype (OS, P < .001; PFS, P < .001). DHS was validated in an independent cohort of 116 patients who were treated with R-CHOP. Conclusion: The immunohistochemical DHS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP.",
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T1 - Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone

AU - Green, Tina Marie

AU - Young, Ken H.

AU - Visco, Carlo

AU - Xu-Monette, Zijun Y.

AU - Orazi, Attilio

AU - Go, Ronald S.

AU - Nielsen, Ole

AU - Gadeberg, Ole V.

AU - Mourits-Andersen, Torben

AU - Frederiksen, Mikael

AU - Pedersen, Lars Møller

AU - Møller, Michael Boe

PY - 2012/10/1

Y1 - 2012/10/1

N2 - Purpose: Approximately 5% of diffuse large B-cell lymphomas (DLBCLs) are double-hit lymphomas (DHLs) with translocations of both MYC and BCL2. DHLs are characterized by poor outcome. We tested whether DLBCLs with high expression of MYC protein and BCL2 protein share the clinical features and poor prognosis of DHLs. Patients and Methods: Paraffin-embedded lymphoma samples from 193 patients with de novo DLBCL who were uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were studied using immunohistochemistry for MYC, BCL2, CD10, BCL6, and MUM1/interferon regulatory factor 4, and fluorescent in situ hybridization (FISH) for MYC and BCL2. Results: FISH analysis identified DHL in 6% of patients, who showed the expected poor overall survival (OS; P = .002). On the basis of immunohistochemical MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group, defined by high expression of both MYC and BCL2 protein, comprised 29% of the patients. DHS 2 was significantly associated with lower complete response rate (P = .004), shorter OS (P < .001), and shorter progression-free survival (PFS; P < .001). The highly significant correlation with OS and PFS was maintained in multivariate models that controlled for the International Prognostic Index and the cell-of-origin subtype (OS, P < .001; PFS, P < .001). DHS was validated in an independent cohort of 116 patients who were treated with R-CHOP. Conclusion: The immunohistochemical DHS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP.

AB - Purpose: Approximately 5% of diffuse large B-cell lymphomas (DLBCLs) are double-hit lymphomas (DHLs) with translocations of both MYC and BCL2. DHLs are characterized by poor outcome. We tested whether DLBCLs with high expression of MYC protein and BCL2 protein share the clinical features and poor prognosis of DHLs. Patients and Methods: Paraffin-embedded lymphoma samples from 193 patients with de novo DLBCL who were uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were studied using immunohistochemistry for MYC, BCL2, CD10, BCL6, and MUM1/interferon regulatory factor 4, and fluorescent in situ hybridization (FISH) for MYC and BCL2. Results: FISH analysis identified DHL in 6% of patients, who showed the expected poor overall survival (OS; P = .002). On the basis of immunohistochemical MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group, defined by high expression of both MYC and BCL2 protein, comprised 29% of the patients. DHS 2 was significantly associated with lower complete response rate (P = .004), shorter OS (P < .001), and shorter progression-free survival (PFS; P < .001). The highly significant correlation with OS and PFS was maintained in multivariate models that controlled for the International Prognostic Index and the cell-of-origin subtype (OS, P < .001; PFS, P < .001). DHS was validated in an independent cohort of 116 patients who were treated with R-CHOP. Conclusion: The immunohistochemical DHS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP.

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