TY - JOUR
T1 - Central nervous system relapse of diffuse large B-cell lymphoma in the rituximab era
T2 - Results of the UK NCRI R-CHOP-14 versus 21 trial
AU - Gleeson, M.
AU - Counsell, N.
AU - Cunningham, David
AU - Chadwick, N.
AU - Lawrie, A.
AU - Hawkes, E. A.
AU - McMillan, A.
AU - Ardeshna, K. M.
AU - Jack, A.
AU - Smith, P.
AU - Mouncey, P.
AU - Pocock, C.
AU - Radford, J. A.
AU - Davies, J.
AU - Turner, D.
AU - Kruger, A.
AU - Johnson, P.
AU - Gambell, J.
AU - Linch, D.
PY - 2017/7/16
Y1 - 2017/7/16
N2 - Background: Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is associated with a dismal prognosis. Here, we report an analysis of CNS relapse for patients treated within the UK NCRI phase III R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) 14 versus 21 randomised trial. Patients and methods: The R-CHOP 14 versus 21 trial compared R-CHOP administered two- versus three weekly in previously untreated patients aged ≥ 18 years with bulky stage I-IV DLBCL (n=1080). Details of CNS prophylaxis were retrospectively collected from participating sites. The incidence and risk factors for CNS relapse including application of the CNS-IPI were evaluated. Results: 177/984 patients (18.0%) received prophylaxis (intrathecal (IT) methotrexate (MTX) n=163, intravenous (IV) MTX n=2, prophylaxis type unknown n=11 and IT MTX and cytarabine n=1). At a median follow-up of 6.5 years, 21 cases of CNS relapse (isolated n=11, with systemic relapse n=10) were observed, with a cumulative incidence of 1.9%. For patients selected to receive prophylaxis, the incidence was 2.8%. Relapses predominantly involved the brain parenchyma (81.0%) and isolated leptomeningeal involvement was rare (14.3%). Univariable analysis demonstrated the following risk factors for CNS relapse: performance status 2, elevated lactate dehydrogenase, IPI,>1 extranodal site of disease and presence of a 'high-risk' extranodal site. Due to the low number of events no factor remained significant in multivariate analysis. Application of the CNS-IPI revealed a high-risk group (4-6 risk factors) with a 2- and 5-year incidence of CNS relapse of 5.2% and 6.8%, respectively. Conclusion: Despite very limited use of IV MTX as prophylaxis, the incidence of CNS relapse following R-CHOP was very low (1.9%) confirming the reduced incidence in the rituximab era. The CNS-IPI identified patients at highest risk for CNS recurrence.
AB - Background: Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is associated with a dismal prognosis. Here, we report an analysis of CNS relapse for patients treated within the UK NCRI phase III R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) 14 versus 21 randomised trial. Patients and methods: The R-CHOP 14 versus 21 trial compared R-CHOP administered two- versus three weekly in previously untreated patients aged ≥ 18 years with bulky stage I-IV DLBCL (n=1080). Details of CNS prophylaxis were retrospectively collected from participating sites. The incidence and risk factors for CNS relapse including application of the CNS-IPI were evaluated. Results: 177/984 patients (18.0%) received prophylaxis (intrathecal (IT) methotrexate (MTX) n=163, intravenous (IV) MTX n=2, prophylaxis type unknown n=11 and IT MTX and cytarabine n=1). At a median follow-up of 6.5 years, 21 cases of CNS relapse (isolated n=11, with systemic relapse n=10) were observed, with a cumulative incidence of 1.9%. For patients selected to receive prophylaxis, the incidence was 2.8%. Relapses predominantly involved the brain parenchyma (81.0%) and isolated leptomeningeal involvement was rare (14.3%). Univariable analysis demonstrated the following risk factors for CNS relapse: performance status 2, elevated lactate dehydrogenase, IPI,>1 extranodal site of disease and presence of a 'high-risk' extranodal site. Due to the low number of events no factor remained significant in multivariate analysis. Application of the CNS-IPI revealed a high-risk group (4-6 risk factors) with a 2- and 5-year incidence of CNS relapse of 5.2% and 6.8%, respectively. Conclusion: Despite very limited use of IV MTX as prophylaxis, the incidence of CNS relapse following R-CHOP was very low (1.9%) confirming the reduced incidence in the rituximab era. The CNS-IPI identified patients at highest risk for CNS recurrence.
KW - Central nervous system
KW - Diffuse large B-cell lymphoma
KW - Relapse
KW - Rituximab
UR - http://www.scopus.com/inward/record.url?scp=85030556751&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdx353
DO - 10.1093/annonc/mdx353
M3 - Article
AN - SCOPUS:85030556751
SN - 0923-7534
VL - 28
SP - 2511
EP - 2516
JO - Annals of Oncology
JF - Annals of Oncology
IS - 10
ER -