Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies

被引：1

作者：

de Groot, Fleur A. ^{[1
]}

Dekker, Tim J. A. ^{[2
]}

Doorduijn, Jeanette K. ^{[3
]}

Bohringer, Stefan ^{[5
,34
]}

Brink, Mirian ^{[4
]}

de Groen, Ruben A. L. ^{[1
]}

de Haan, Lorraine M. ^{[6
]}

Woei-A-Jin, F. J. Sherida H. ^{[7
]}

Noordenbos, Troy ^{[6
]}

Sijs-Szabo, Aniko ^{[1
]}

Oudshoorn, Mirjam A. ^{[1
]}

Lam, King H. ^{[8
]}

Diepstra, Arjan ^{[9
]}

te Boome, Liane C. J. ^{[10
]}

Terpstra, Valeska ^{[11
]}

Bohmer, Lara H. ^{[12
]}

Nicolae, Alina ^{[13
]}

Posthuma, Eduardus F. M. ^{[14
]}

Koens, Lianne

Durian, Marc F. ^{[15
,16
]}

Stavast, Jeroen ^{[17
]}

van der Poel, Marjolein W. M. ^{[18
]}

Hamid, Myrurgia Abdul ^{[19
]}

Stevens, Wendy B. C. ^{[20
]}

van Rooij, Sjo L. M. ^{[21
]}

Oostvogels, Rimke S. ^{[22
]}

Muhlebner, Angelika ^{[23
]}

Neelis, Karen J. ^{[24
]}

van den Brand, Michiel ^{[25
]}

Tousseyn, Thomas ^{[26
]}

Dierickx, Daan ^{[27
]}

de Weerdt, Okke ^{[28
]}

Beeker, Aart ^{[29
]}

Jansen, Patty M. ^{[6
]}

Kersten, Marie Jose ^{[30
,31
]}

Zijlstra, Josee M. ^{[30
,31
]}

Chamuleau, Martine E. D. ^{[30
,31
]}

Veelken, Hendrik ^{[1
]}

Bromberg, Jacoline C. E. ^{[32
]}

Nijland, Marcel ^{[33
]}

Vermaat, Joost S. P. ^{[1
]}

机构：

[1] Leiden Univ, Dept Hematol, Med Ctr, POB 9600, NL-2300 RC Leiden, Netherlands

[2] Leiden Univ, Med Ctr, Dept Internal Med, Leiden, Netherlands

[3] Univ Med Ctr Rotterdam, Erasmus MC Canc Inst, Dept Hematol, Rotterdam, Netherlands

[4] Netherlands Comprehens Canc Org IKNL, Dept Res & Dev, Utrecht, Netherlands

[5] Leiden Univ, Med Ctr, Dept Biomed Data Sci, Leiden, Netherlands

[6] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands

[7] Univ Hosp Leuven, Dept Gen Med Oncol, Leuven, Belgium

[8] Erasmus MC, Dept Pathol, Rotterdam, Netherlands

[9] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Groningen, Netherlands

[10] Haaglanden Med Ctr, Dept Hematol, The Hague, Netherlands

[11] Haaglanden Med Ctr, Dept Pathol, The Hague, Netherlands

[12] Haga Teaching Hosp, Dept Biostat, The Hague, Netherlands

[13] Haga Teaching Hosp, Dept Neurol, The Hague, Netherlands

[14] Reinier de Graaf Gasthuis, Dept Internal Med, Delt, Netherlands

[15] Univ Amsterdam, Amsterdam Univ Med Ctr, Med Ctr, Amsterdam, Netherlands

[16] Elisabeth TweeSteden Ziekenhuis Tilburg, Dept Hematol, Tilburg, Netherlands

[17] Elisabeth TweeSteden Ziekenhuis Tilburg, Dept Pathol, Tilburg, Netherlands

[18] Maastricht Univ, GROW Sch Oncol & Dev Biol, Dept Internal Med, Div Hematol,Med Ctr, Maastricht, Netherlands

[19] Maastricht Univ, Dept Pathol, Med Ctr, Maastricht, Netherlands

[20] Radboud Univ Nijmegen, Dept Hematol, Med Ctr, Nijmegen, Netherlands

[21] Univ Med Ctr Utrecht, Dept Neurol, Utrecht, Netherlands

[22] Univ Med Ctr Utrecht, Dept Hematol, Utrecht, Netherlands

[23] Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands

[24] Leiden Univ, Med Ctr, Dept Radiotherapy, Leiden, Netherlands

[25] Radboud Univ Nijmegen, Dept Pathol, Med Ctr, Nijmegen, Netherlands

[26] Univ Hosp Leuven, Dept Pathol, Leuven, Belgium

[27] Univ Hosp Leuven, Dept Hematol, Leuven, Belgium

[28] St Antonius Hosp, Dept Internal Med, Nieuwegein, Netherlands

[29] Spaarne Gasthuis, Dept Internal Med, Haarlem, Netherlands

[30] Univ Amsterdam, Dept Hematol, Canc Ctr Amsterdam, Med Ctr, Amsterdam, Netherlands

[31] LYMMCARE, Amsterdam, Netherlands

[32] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands

[33] Univ Groningen, Univ Med Ctr Groningen, Dept Hematol, Groningen, Netherlands

[34] Leiden Univ, Med Ctr, Med Ctr, Leiden, Netherlands

来源：

EUROPEAN JOURNAL OF CANCER | 2024年 / 213卷

关键词：

PCNSL; Clinical characteristics; Survival outcomes; High-dose methotrexate; Induction; Polychemotherapy; Consolidation; PRIMARY CNS LYMPHOMA; INTERNATIONAL EXTRANODAL LYMPHOMA; HEALTH-ORGANIZATION CLASSIFICATION; STEM-CELL TRANSPLANTATION; CHEMOTHERAPY; RADIOTHERAPY; CHEMOIMMUNOTHERAPY; RANDOMIZATION; RITUXIMAB;

D O I：

10.1016/j.ejca.2024.115068

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with >= 1 cycle HD-MTX-based strategies (>= 3g/m(2)/cycle) were included. The regimens included MATRIX (HD-MTX, HD-AraC, thiotepa, and rituximab), (R)MBVP +/- HD-AraC (HD-MTX, teniposide/etoposide, carmustine, prednisolone, +/- HD-AraC, +/- rituximab), (R)MP (HD-MTX, procarbazine, +/- rituximab), and a combination of HD-MTX and HD-AraC. The overall response rate after induction was 69 %, 28 % complete remission and progressive disease was observed in 100 (29 %) patients. 126 (36 %) patients received consolidation, including high-dose-BCNU-thiotepa with autologous stem cell transplantation (HD-BCNU-TT/ASCT, n = 59 (17 %)) or whole brain radiotherapy (WBRT, n = 67 (19 %)). Clinical characteristics associated with adverse mortality risk by multivariable prognostication contained age > 60 years (HR 1.61, p = 0.011), elevated LDH (HR 1.75, p = 0.004) and WHO status >= 2 (HR 1.56, p = 0.010). Independently, induction regimens containing HD-AraC demonstrated survival benefit compared to induction regimens without HD-AraC (HR 0.59, p = 0.002). Without preference for HD-BCNU-TT/ASCT or WBRT, a favorable effect of consolidation (HR 0.44 and HR 0.42, p < 0.001) was confirmed, also with consolidation as time-dependent variable. Competing risk analysis showed similar low incidence of lymphoma-unrelated deaths in consolidated and unconsolidated patients. This study confirms that age, elevated LDH and WHO status increase the mortality risk. HD-AraC containing treatment regimens and consolidation with HD-BCU-TT/ASCT or WBRT were associated with superior survival, including a favorable low incidence of lymphoma-unrelated deaths.

引用

页数：9

共 50 条

[1] Relapse of primary central nervous system lymphoma 13 years after high-dose methotrexate-based polychemotherapy
Steinbeck, J. A.
Stuplich, M.
Blasius, E.
Pels, H.
Glas, M.
Schlegel, U.
Herrlinger, U.
JOURNAL OF CLINICAL NEUROSCIENCE, 2011, 18 (11) : 1554 - 1555
[2] Outcomes of older patients with primary central nervous system lymphoma treated in routine clinical practice in the UK: methotrexate dose intensity correlates with response and survival
Martinez-Calle, Nicolas
Poynton, Edward
Alchawaf, Alia
Kassam, Shireen
Horan, Matthew
Rafferty, Mark
Kelsey, Phillipa
Scott, Gemma
Culligan, Dominic J.
Buckley, Hannah
Lim, Yeong Y.
Ngu, Loretta
McCulloch, Rory
Rowntree, Clare
Wright, Josh
McKay, Pamela
Fourali, Samih
Eyre, Toby A.
Smith, Jeffrey
Osborne, Wendy
Yallop, Deborah
Linton, Kim
Fox, Christopher P.
Cwynarski, Kate
BRITISH JOURNAL OF HAEMATOLOGY, 2020, 190 (03) : 394 - 404
[3] Improvement of outcomes of an escalated high-dose methotrexate-based regimen for patients with newly diagnosed primary central nervous system lymphoma: a real-world cohort study
Li, Qing
Ma, Jingjing
Ma, Yan
Lin, Zhiguang
Kang, Hui
Chen, Bobin
CANCER MANAGEMENT AND RESEARCH, 2021, 13 : 6115 - 6122
[4] A Systematic Review of High-Dose Methotrexate for Adults with Primary Central Nervous System Lymphoma
Villanueva, Gabriela
Guscott, Martin
Schaiquevich, Paula
Sampor, Claudia
Combs, Ryan
Tentoni, Nicolas
Hwang, Miriam
Lowe, Jennifer
Howard, Scott
CANCERS, 2023, 15 (05)
[5] Prognostic Role of Blood Markers in Primary Central Nervous System Lymphoma Patients Treated With High-Dose Methotrexate-Based Therapy
Luo, Qian
Yang, Chunli
Fu, Chunxi
Wu, Wanchun
Wei, Yi
Zou, Liqun
FRONTIERS IN ONCOLOGY, 2021, 11
[6] High-dose methotrexate dosing strategy in primary central nervous system lymphoma
Wang, Alexander
Cirrone, Frank
De los Reyes, Francis Andrew
Papadopoulos, John
Saint Fleur-Lominy, Shella
Xiang, Elaine
LEUKEMIA & LYMPHOMA, 2022, 63 (06) : 1348 - 1355
[7] High-dose methotrexate-based regimens with or without vincristine for the treatment of primary central nervous system lymphoma
Freeman, Tracelyn
Legasto, Carlo S.
Schickli, M. Alexandra
McLaughlin, Eric M.
Giglio, Pierre
Puduvalli, Vinay
Gonzalez, Javier
NEURO-ONCOLOGY ADVANCES, 2020, 2 (01)
[8] Clinical outcomes of patients with newly diagnosed primary central nervous system lymphoma are comparable on treatment with high-dose methotrexate plus temozolomide and with high-dose methotrexate plus cytarabine: a single-institution experience
Wang, Xiao-xiao
Huang, Hui-qiang
Bai, Bing
Cai, Qing-qing
Cai, Qi-chun
Gao, Yan
Xia, Yun-fei
Xia, Zhong-jun
Jiang, Wen-qi
LEUKEMIA & LYMPHOMA, 2014, 55 (11) : 2497 - 2501
[9] Management of Patients With Primary Central Nervous System Lymphoma Treated With High-Dose Methotrexate
Warnick, Elizabeth
Auger, Danielle
CLINICAL JOURNAL OF ONCOLOGY NURSING, 2009, 13 (02) : 177 - 180
[10] Efficacy and safety of high-dose etoposide cytarabine as consolidation following rituximab methotrexate temozolomide induction in newly diagnosed primary central nervous system lymphoma in immunocompetent patients
Birsen, Rudy
Willems, Lise
Pallud, Johan
Blanc, Estelle
Burroni, Barbara
Legoff, Marielle
Le Ray, Emmanuelle
Pilorge, Sylvain
Deau, Benedicte
Franchi, Patricia
Vignon, Marguerite
Kirova, Yioula
Edjlali, Myriam
Houillier, Caroline
Soussain, Carole
Varlet, Pascale
Dezamis, Edouard
Damotte, Diane
Bouscary, Didier
Tamburini, Jerome
HAEMATOLOGICA, 2018, 103 (07) : E296 - E299

← 1 2 3 4 5 →