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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
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.
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