TY - JOUR
T1 - Treatment of secondary central nervous system lymphoma with intrathecal rituximab, high-dose methotrexate, and R-DHAP followed by autologous stem cell transplantation
T2 - results of the HOVON 80 phase 2 study
AU - Doorduijn, Jeanette K.
AU - van Imhoff, Gustaaf W.
AU - van der Holt, Bronno
AU - Schouten, Harry C.
AU - Schaafsma, Martijn R.
AU - MacKenzie, Marius A.
AU - Baars, Joke W.
AU - Kersten, Marie Jose
AU - Lugtenburg, Pieternella J.
AU - van den Bent, Martin J.
AU - Enting, Roelien H.
AU - Spoelstra, Fokje M.
AU - Poortmans, Philip
AU - Bromberg, Jacoline E. C.
PY - 2017/12
Y1 - 2017/12
N2 - The prognosis of central nervous system (CNS) relapse of systemic non-Hodgkin lymphoma is poor with 1-year survival historically at 0% to 20%. Aiming to improve these results, we performed a multicenter phase 2 study in patients with a CNS relapse, with or without concurrent systemic relapse. Treatment consisted of 2 cycles of R-DHAP alternating with high-dose methotrexate (MTX) and was combined with intrathecal rituximab. Responding patients received a third R-DHAP-MTX cycle followed by busulfan and cyclophosphamide myeloablative therapy and autologous stem cell transplantation. In patients with persistent cerebrospinal fluid lymphoma after cycle 1, the intrathecal rituximab was replaced by intrathecal triple therapy, with MTX, cytarabine, and dexamethasone.Thirty-six patients were included. Eighteen had evidence of cerebrospinal fluid lymphoma, 24 had brain parenchymal disease, and 20 (56%) had concurrent systemic disease. The overall response rate after 2 R-DHAP-MTX was 53% (19/36), with 22% (8/36) complete remission. Fifteen patients (42%) underwent a transplant. One-year progression-free survival was 19% (95% confidence interval, 9-34): 25% in patients without and 15% in patients with systemic disease. One-year overall survival was 25% (95% confidence interval, 12-40). This treatment regimen did not result in a major improvement of outcome of secondary CNS lymphoma, especially when concurrent systemic disease was present.Registered in the Dutch trial register www. trialregister.nl, NTR1757; EudraCT number 2006-002141-37.
AB - The prognosis of central nervous system (CNS) relapse of systemic non-Hodgkin lymphoma is poor with 1-year survival historically at 0% to 20%. Aiming to improve these results, we performed a multicenter phase 2 study in patients with a CNS relapse, with or without concurrent systemic relapse. Treatment consisted of 2 cycles of R-DHAP alternating with high-dose methotrexate (MTX) and was combined with intrathecal rituximab. Responding patients received a third R-DHAP-MTX cycle followed by busulfan and cyclophosphamide myeloablative therapy and autologous stem cell transplantation. In patients with persistent cerebrospinal fluid lymphoma after cycle 1, the intrathecal rituximab was replaced by intrathecal triple therapy, with MTX, cytarabine, and dexamethasone.Thirty-six patients were included. Eighteen had evidence of cerebrospinal fluid lymphoma, 24 had brain parenchymal disease, and 20 (56%) had concurrent systemic disease. The overall response rate after 2 R-DHAP-MTX was 53% (19/36), with 22% (8/36) complete remission. Fifteen patients (42%) underwent a transplant. One-year progression-free survival was 19% (95% confidence interval, 9-34): 25% in patients without and 15% in patients with systemic disease. One-year overall survival was 25% (95% confidence interval, 12-40). This treatment regimen did not result in a major improvement of outcome of secondary CNS lymphoma, especially when concurrent systemic disease was present.Registered in the Dutch trial register www. trialregister.nl, NTR1757; EudraCT number 2006-002141-37.
KW - clinical trial
KW - methotrexate
KW - rituximab
KW - secondary CNS lymphoma
KW - transplantation
KW - treatment
KW - NON-HODGKINS-LYMPHOMA
KW - PRIMARY CNS LYMPHOMA
KW - MABTHERA INTERNATIONAL TRIAL
KW - CHEMOTHERAPY PLUS RITUXIMAB
KW - STUDY-GROUP DSHNHL
KW - AGGRESSIVE LYMPHOMA
KW - ELDERLY-PATIENTS
KW - MARROW-TRANSPLANTATION
KW - INTRAOCULAR LYMPHOMA
KW - RESPONSE CRITERIA
U2 - 10.1002/hon.2342
DO - 10.1002/hon.2342
M3 - Article
C2 - 27530779
VL - 35
SP - 497
EP - 503
JO - Hematological Oncology
JF - Hematological Oncology
SN - 0278-0232
IS - 4
ER -