Inferior survival in high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements is not associated with MYC/IG gene rearrangements

Ellen McPhail, Matthew J. Maurer, William R. Macon, Andrew L Feldman, Paul J. Kurtin, Rhett P. Ketterling, Rakhee Vaidya, James R Cerhan, Stephen Maxted Ansell, Luis F. Porrata, Grzegorz S Nowakowski, Thomas Elmer Witzig, Thomas Matthew Habermann

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Abstract

High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements (double-/triple-hit lymphoma) have an aggressive clinical course. We investigated the prognostic value of transformation from low-grade lymphoma, cytological features (high grade versus large cell), MYC rearrangement partners (immunoglobulin versus nonimmunoglobulin gene), and treatment. We evaluated 100 adults with double-/triple-hit lymphoma, reviewing cytological features; cell of origin; and rearrangements of MYC, BCL2, and BCL6 using MYC, BCL2, and BCL6 break-apart and IGH/MYC, IGL/MYC, IGK/MYC, and IGH/BCL2 dual-fusion interphase fluorescence in situ hybridization probes. Outcome analysis was restricted to patients with lymphoma, de novo or at transformation, who received anthracycline-based chemotherapy. Among them, 60% had high-grade cytological features; 91% had a germinal center B-cell phenotype, and 60% had a MYC/IG rearrangement. Germinal center B-cell phenotype was associated with BCL2 rearrangements (P<0.001). Mean (95% confidence interval) 5-year overall survival was 49% (37%-64%). Transformation from previously treated and untreated low-grade lymphoma was associated with inferior overall survival (hazard ratio, 2.99; P=0.008). Patients with high-grade cytological features showed a non-significant tendency to inferior outcome (hazard ratio, 2.32; P=0.09). No association was observed between MYC rearrangement partner and overall survival (hazard ratio, 1.00; P=0.99). Compared with patients receiving rituximab, cyclophosphamide, doxorubicin, and vincristine (R-CHOP) and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R), patients receiving rituximab, cyclophosphamide, vincristine, doxorubicin, methotrexate/ifosfamide, etoposide, and cytarabine (R-CODOX-M/IVAC) had a non-significant tendency to better overall survival (hazard ratio, 0.37; P=0.10). In conclusion, high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements had heterogeneous outcomes and MYC/IG rearrangements were not associated with inferior overall survival.

Original languageEnglish (US)
Pages (from-to)1899-1907
Number of pages9
JournalHaematologica
Volume103
Issue number11
DOIs
StatePublished - Nov 1 2018

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Gene Rearrangement
B-Cell Lymphoma
Non-Hodgkin's Lymphoma
Vincristine
Survival
Doxorubicin
Cyclophosphamide
Lymphoma
Germinal Center
Etoposide
B-Lymphocytes
Phenotype
Ifosfamide
Anthracyclines
Cytarabine
Interphase
Prednisone
Fluorescence In Situ Hybridization
Methotrexate
Immunoglobulins

ASJC Scopus subject areas

  • Hematology

Cite this

Inferior survival in high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements is not associated with MYC/IG gene rearrangements. / McPhail, Ellen; Maurer, Matthew J.; Macon, William R.; Feldman, Andrew L; Kurtin, Paul J.; Ketterling, Rhett P.; Vaidya, Rakhee; Cerhan, James R; Ansell, Stephen Maxted; Porrata, Luis F.; Nowakowski, Grzegorz S; Witzig, Thomas Elmer; Habermann, Thomas Matthew.

In: Haematologica, Vol. 103, No. 11, 01.11.2018, p. 1899-1907.

Research output: Contribution to journalArticle

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title = "Inferior survival in high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements is not associated with MYC/IG gene rearrangements",
abstract = "High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements (double-/triple-hit lymphoma) have an aggressive clinical course. We investigated the prognostic value of transformation from low-grade lymphoma, cytological features (high grade versus large cell), MYC rearrangement partners (immunoglobulin versus nonimmunoglobulin gene), and treatment. We evaluated 100 adults with double-/triple-hit lymphoma, reviewing cytological features; cell of origin; and rearrangements of MYC, BCL2, and BCL6 using MYC, BCL2, and BCL6 break-apart and IGH/MYC, IGL/MYC, IGK/MYC, and IGH/BCL2 dual-fusion interphase fluorescence in situ hybridization probes. Outcome analysis was restricted to patients with lymphoma, de novo or at transformation, who received anthracycline-based chemotherapy. Among them, 60{\%} had high-grade cytological features; 91{\%} had a germinal center B-cell phenotype, and 60{\%} had a MYC/IG rearrangement. Germinal center B-cell phenotype was associated with BCL2 rearrangements (P<0.001). Mean (95{\%} confidence interval) 5-year overall survival was 49{\%} (37{\%}-64{\%}). Transformation from previously treated and untreated low-grade lymphoma was associated with inferior overall survival (hazard ratio, 2.99; P=0.008). Patients with high-grade cytological features showed a non-significant tendency to inferior outcome (hazard ratio, 2.32; P=0.09). No association was observed between MYC rearrangement partner and overall survival (hazard ratio, 1.00; P=0.99). Compared with patients receiving rituximab, cyclophosphamide, doxorubicin, and vincristine (R-CHOP) and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R), patients receiving rituximab, cyclophosphamide, vincristine, doxorubicin, methotrexate/ifosfamide, etoposide, and cytarabine (R-CODOX-M/IVAC) had a non-significant tendency to better overall survival (hazard ratio, 0.37; P=0.10). In conclusion, high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements had heterogeneous outcomes and MYC/IG rearrangements were not associated with inferior overall survival.",
author = "Ellen McPhail and Maurer, {Matthew J.} and Macon, {William R.} and Feldman, {Andrew L} and Kurtin, {Paul J.} and Ketterling, {Rhett P.} and Rakhee Vaidya and Cerhan, {James R} and Ansell, {Stephen Maxted} and Porrata, {Luis F.} and Nowakowski, {Grzegorz S} and Witzig, {Thomas Elmer} and Habermann, {Thomas Matthew}",
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T1 - Inferior survival in high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements is not associated with MYC/IG gene rearrangements

AU - McPhail, Ellen

AU - Maurer, Matthew J.

AU - Macon, William R.

AU - Feldman, Andrew L

AU - Kurtin, Paul J.

AU - Ketterling, Rhett P.

AU - Vaidya, Rakhee

AU - Cerhan, James R

AU - Ansell, Stephen Maxted

AU - Porrata, Luis F.

AU - Nowakowski, Grzegorz S

AU - Witzig, Thomas Elmer

AU - Habermann, Thomas Matthew

PY - 2018/11/1

Y1 - 2018/11/1

N2 - High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements (double-/triple-hit lymphoma) have an aggressive clinical course. We investigated the prognostic value of transformation from low-grade lymphoma, cytological features (high grade versus large cell), MYC rearrangement partners (immunoglobulin versus nonimmunoglobulin gene), and treatment. We evaluated 100 adults with double-/triple-hit lymphoma, reviewing cytological features; cell of origin; and rearrangements of MYC, BCL2, and BCL6 using MYC, BCL2, and BCL6 break-apart and IGH/MYC, IGL/MYC, IGK/MYC, and IGH/BCL2 dual-fusion interphase fluorescence in situ hybridization probes. Outcome analysis was restricted to patients with lymphoma, de novo or at transformation, who received anthracycline-based chemotherapy. Among them, 60% had high-grade cytological features; 91% had a germinal center B-cell phenotype, and 60% had a MYC/IG rearrangement. Germinal center B-cell phenotype was associated with BCL2 rearrangements (P<0.001). Mean (95% confidence interval) 5-year overall survival was 49% (37%-64%). Transformation from previously treated and untreated low-grade lymphoma was associated with inferior overall survival (hazard ratio, 2.99; P=0.008). Patients with high-grade cytological features showed a non-significant tendency to inferior outcome (hazard ratio, 2.32; P=0.09). No association was observed between MYC rearrangement partner and overall survival (hazard ratio, 1.00; P=0.99). Compared with patients receiving rituximab, cyclophosphamide, doxorubicin, and vincristine (R-CHOP) and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R), patients receiving rituximab, cyclophosphamide, vincristine, doxorubicin, methotrexate/ifosfamide, etoposide, and cytarabine (R-CODOX-M/IVAC) had a non-significant tendency to better overall survival (hazard ratio, 0.37; P=0.10). In conclusion, high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements had heterogeneous outcomes and MYC/IG rearrangements were not associated with inferior overall survival.

AB - High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements (double-/triple-hit lymphoma) have an aggressive clinical course. We investigated the prognostic value of transformation from low-grade lymphoma, cytological features (high grade versus large cell), MYC rearrangement partners (immunoglobulin versus nonimmunoglobulin gene), and treatment. We evaluated 100 adults with double-/triple-hit lymphoma, reviewing cytological features; cell of origin; and rearrangements of MYC, BCL2, and BCL6 using MYC, BCL2, and BCL6 break-apart and IGH/MYC, IGL/MYC, IGK/MYC, and IGH/BCL2 dual-fusion interphase fluorescence in situ hybridization probes. Outcome analysis was restricted to patients with lymphoma, de novo or at transformation, who received anthracycline-based chemotherapy. Among them, 60% had high-grade cytological features; 91% had a germinal center B-cell phenotype, and 60% had a MYC/IG rearrangement. Germinal center B-cell phenotype was associated with BCL2 rearrangements (P<0.001). Mean (95% confidence interval) 5-year overall survival was 49% (37%-64%). Transformation from previously treated and untreated low-grade lymphoma was associated with inferior overall survival (hazard ratio, 2.99; P=0.008). Patients with high-grade cytological features showed a non-significant tendency to inferior outcome (hazard ratio, 2.32; P=0.09). No association was observed between MYC rearrangement partner and overall survival (hazard ratio, 1.00; P=0.99). Compared with patients receiving rituximab, cyclophosphamide, doxorubicin, and vincristine (R-CHOP) and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R), patients receiving rituximab, cyclophosphamide, vincristine, doxorubicin, methotrexate/ifosfamide, etoposide, and cytarabine (R-CODOX-M/IVAC) had a non-significant tendency to better overall survival (hazard ratio, 0.37; P=0.10). In conclusion, high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements had heterogeneous outcomes and MYC/IG rearrangements were not associated with inferior overall survival.

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