Outcomes of synchronous systemic and central nervous system (CNS) involvement of diffuse large B-cell lymphoma are dictated by the CNS disease: a collaborative study of the Australasian Lymphoma Alliance

Joel C. Wight, Mimi Yue, Colm Keane, Anna Johnston, Kim Linton, Collin Chin, Shin Hnin Wai, Dipti Talaulikar, Robin Gasiorowski, Chan Yoon Cheah, Gareth P. Gregory, Michael Dickinson, Adrian Minson, Caitlin Coombes, Matthew Ku, Stephanie Lam, Eliza A. Hawkes

Research output: Contribution to journalArticle

Abstract

De novo diffuse large B-cell lymphoma (DLBCL) presenting with synchronous central nervous system (CNS) and systemic disease (synDLBCL) is not well described and is excluded from clinical trials. We performed a retrospective analysis of 80 synDLBCL patients treated across 10 Australian and UK centres. Of these patients, 96% had extranodal systemic disease. CNS-directed treatment with combination intravenous cytarabine and high-dose methotrexate (“CNS-intensive”) (n = 38) was associated with favourable survival outcomes compared with “CNS-conservative” strategies such as intravenous high-dose methotrexate monotherapy, intrathecal therapy and/or radiotherapy (2-year progression-free survival [PFS] 50% vs. 31%, P = 0·006; 2-year overall survival [OS] 54% vs. 44%, P = 0·037). Outcomes were primarily dictated by the ability to control the CNS disease, with 2-year cumulative CNS relapse incidence of 42% and non-CNS relapse 21%. Two-year OS for CNS-relapse patients was 13% vs. 36% for non-CNS relapses (P = 0·02). Autologous stem cell transplantation as consolidation (n = 14) was not observed to improve survival in those patients who received CNS-intensive induction when matched for induction outcomes (2-year PFS 69% vs. 56%, P = 0·99; 2-year OS 66% vs. 56%, P = 0·98). Hyperfractionated or infusional systemic treatment did not improve survival compared to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) (2-year OS 49% for both groups). Our study suggests that adequate control of the CNS disease is paramount and is best achieved by intensive CNS-directed induction.

Original languageEnglish
JournalBritish Journal of Haematology
DOIs
Publication statusPublished - 1 Jan 2019

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Lymphoma, Large B-Cell, Diffuse
Central Nervous System Diseases
Lymphoma
Central Nervous System
Survival
Recurrence
Methotrexate
Nervous System
Disease-Free Survival
Cytarabine
Stem Cell Transplantation
Vincristine
Prednisolone
Doxorubicin
Cyclophosphamide
Radiotherapy
Therapeutics
Clinical Trials
Incidence

Cite this

Wight, Joel C. ; Yue, Mimi ; Keane, Colm ; Johnston, Anna ; Linton, Kim ; Chin, Collin ; Wai, Shin Hnin ; Talaulikar, Dipti ; Gasiorowski, Robin ; Yoon Cheah, Chan ; Gregory, Gareth P. ; Dickinson, Michael ; Minson, Adrian ; Coombes, Caitlin ; Ku, Matthew ; Lam, Stephanie ; Hawkes, Eliza A. / Outcomes of synchronous systemic and central nervous system (CNS) involvement of diffuse large B-cell lymphoma are dictated by the CNS disease : a collaborative study of the Australasian Lymphoma Alliance. In: British Journal of Haematology. 2019.
@article{fbf3bdaa316e43d3879f6b7020036042,
title = "Outcomes of synchronous systemic and central nervous system (CNS) involvement of diffuse large B-cell lymphoma are dictated by the CNS disease: a collaborative study of the Australasian Lymphoma Alliance",
abstract = "De novo diffuse large B-cell lymphoma (DLBCL) presenting with synchronous central nervous system (CNS) and systemic disease (synDLBCL) is not well described and is excluded from clinical trials. We performed a retrospective analysis of 80 synDLBCL patients treated across 10 Australian and UK centres. Of these patients, 96{\%} had extranodal systemic disease. CNS-directed treatment with combination intravenous cytarabine and high-dose methotrexate (“CNS-intensive”) (n = 38) was associated with favourable survival outcomes compared with “CNS-conservative” strategies such as intravenous high-dose methotrexate monotherapy, intrathecal therapy and/or radiotherapy (2-year progression-free survival [PFS] 50{\%} vs. 31{\%}, P = 0·006; 2-year overall survival [OS] 54{\%} vs. 44{\%}, P = 0·037). Outcomes were primarily dictated by the ability to control the CNS disease, with 2-year cumulative CNS relapse incidence of 42{\%} and non-CNS relapse 21{\%}. Two-year OS for CNS-relapse patients was 13{\%} vs. 36{\%} for non-CNS relapses (P = 0·02). Autologous stem cell transplantation as consolidation (n = 14) was not observed to improve survival in those patients who received CNS-intensive induction when matched for induction outcomes (2-year PFS 69{\%} vs. 56{\%}, P = 0·99; 2-year OS 66{\%} vs. 56{\%}, P = 0·98). Hyperfractionated or infusional systemic treatment did not improve survival compared to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) (2-year OS 49{\%} for both groups). Our study suggests that adequate control of the CNS disease is paramount and is best achieved by intensive CNS-directed induction.",
keywords = "central nervous system lymphoma, cytarabine, de novo diffuse large B-cell lymphoma, synchronous lymphoma",
author = "Wight, {Joel C.} and Mimi Yue and Colm Keane and Anna Johnston and Kim Linton and Collin Chin and Wai, {Shin Hnin} and Dipti Talaulikar and Robin Gasiorowski and {Yoon Cheah}, Chan and Gregory, {Gareth P.} and Michael Dickinson and Adrian Minson and Caitlin Coombes and Matthew Ku and Stephanie Lam and Hawkes, {Eliza A.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/bjh.16064",
language = "English",
journal = "British Journal of Haematology",
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Wight, JC, Yue, M, Keane, C, Johnston, A, Linton, K, Chin, C, Wai, SH, Talaulikar, D, Gasiorowski, R, Yoon Cheah, C, Gregory, GP, Dickinson, M, Minson, A, Coombes, C, Ku, M, Lam, S & Hawkes, EA 2019, 'Outcomes of synchronous systemic and central nervous system (CNS) involvement of diffuse large B-cell lymphoma are dictated by the CNS disease: a collaborative study of the Australasian Lymphoma Alliance' British Journal of Haematology. https://doi.org/10.1111/bjh.16064

Outcomes of synchronous systemic and central nervous system (CNS) involvement of diffuse large B-cell lymphoma are dictated by the CNS disease : a collaborative study of the Australasian Lymphoma Alliance. / Wight, Joel C.; Yue, Mimi; Keane, Colm; Johnston, Anna; Linton, Kim; Chin, Collin; Wai, Shin Hnin; Talaulikar, Dipti; Gasiorowski, Robin; Yoon Cheah, Chan; Gregory, Gareth P.; Dickinson, Michael; Minson, Adrian; Coombes, Caitlin; Ku, Matthew; Lam, Stephanie; Hawkes, Eliza A.

In: British Journal of Haematology, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Outcomes of synchronous systemic and central nervous system (CNS) involvement of diffuse large B-cell lymphoma are dictated by the CNS disease

T2 - a collaborative study of the Australasian Lymphoma Alliance

AU - Wight, Joel C.

AU - Yue, Mimi

AU - Keane, Colm

AU - Johnston, Anna

AU - Linton, Kim

AU - Chin, Collin

AU - Wai, Shin Hnin

AU - Talaulikar, Dipti

AU - Gasiorowski, Robin

AU - Yoon Cheah, Chan

AU - Gregory, Gareth P.

AU - Dickinson, Michael

AU - Minson, Adrian

AU - Coombes, Caitlin

AU - Ku, Matthew

AU - Lam, Stephanie

AU - Hawkes, Eliza A.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - De novo diffuse large B-cell lymphoma (DLBCL) presenting with synchronous central nervous system (CNS) and systemic disease (synDLBCL) is not well described and is excluded from clinical trials. We performed a retrospective analysis of 80 synDLBCL patients treated across 10 Australian and UK centres. Of these patients, 96% had extranodal systemic disease. CNS-directed treatment with combination intravenous cytarabine and high-dose methotrexate (“CNS-intensive”) (n = 38) was associated with favourable survival outcomes compared with “CNS-conservative” strategies such as intravenous high-dose methotrexate monotherapy, intrathecal therapy and/or radiotherapy (2-year progression-free survival [PFS] 50% vs. 31%, P = 0·006; 2-year overall survival [OS] 54% vs. 44%, P = 0·037). Outcomes were primarily dictated by the ability to control the CNS disease, with 2-year cumulative CNS relapse incidence of 42% and non-CNS relapse 21%. Two-year OS for CNS-relapse patients was 13% vs. 36% for non-CNS relapses (P = 0·02). Autologous stem cell transplantation as consolidation (n = 14) was not observed to improve survival in those patients who received CNS-intensive induction when matched for induction outcomes (2-year PFS 69% vs. 56%, P = 0·99; 2-year OS 66% vs. 56%, P = 0·98). Hyperfractionated or infusional systemic treatment did not improve survival compared to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) (2-year OS 49% for both groups). Our study suggests that adequate control of the CNS disease is paramount and is best achieved by intensive CNS-directed induction.

AB - De novo diffuse large B-cell lymphoma (DLBCL) presenting with synchronous central nervous system (CNS) and systemic disease (synDLBCL) is not well described and is excluded from clinical trials. We performed a retrospective analysis of 80 synDLBCL patients treated across 10 Australian and UK centres. Of these patients, 96% had extranodal systemic disease. CNS-directed treatment with combination intravenous cytarabine and high-dose methotrexate (“CNS-intensive”) (n = 38) was associated with favourable survival outcomes compared with “CNS-conservative” strategies such as intravenous high-dose methotrexate monotherapy, intrathecal therapy and/or radiotherapy (2-year progression-free survival [PFS] 50% vs. 31%, P = 0·006; 2-year overall survival [OS] 54% vs. 44%, P = 0·037). Outcomes were primarily dictated by the ability to control the CNS disease, with 2-year cumulative CNS relapse incidence of 42% and non-CNS relapse 21%. Two-year OS for CNS-relapse patients was 13% vs. 36% for non-CNS relapses (P = 0·02). Autologous stem cell transplantation as consolidation (n = 14) was not observed to improve survival in those patients who received CNS-intensive induction when matched for induction outcomes (2-year PFS 69% vs. 56%, P = 0·99; 2-year OS 66% vs. 56%, P = 0·98). Hyperfractionated or infusional systemic treatment did not improve survival compared to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) (2-year OS 49% for both groups). Our study suggests that adequate control of the CNS disease is paramount and is best achieved by intensive CNS-directed induction.

KW - central nervous system lymphoma

KW - cytarabine

KW - de novo diffuse large B-cell lymphoma

KW - synchronous lymphoma

UR - http://www.scopus.com/inward/record.url?scp=85068051414&partnerID=8YFLogxK

U2 - 10.1111/bjh.16064

DO - 10.1111/bjh.16064

M3 - Article

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

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