Timing of high-dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1384 patients.

Autor:	Wilson MR; Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom., Eyre TA; Oxford University Hospitals NHS Trust, Churchill Cancer Center, Oxford, United Kingdom., Kirkwood AA; Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, United Kingdom., Wong Doo N; Concord Clinical School, Concord Hospital University of Sydney, Sydney, NSW, Australia., Soussain C; Institut Curie Hôpital René Huguenin, Saint-Cloud, France., Choquet S; La Pitie Salpetriere Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP)-Sorbonne Universite, Paris, France., Martinez-Calle N; Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom., Preston G; Aberdeen Royal Infirmary, Aberdeen, United Kingdom., Ahearne M; University Hospitals of Leicester NHS Trust, Leicester, United Kingdom., Schorb E; Department of Medicine, University Medical Center Freiburg, Freiburg, Germany., Moles-Moreau MP; Service des Maladies du Sang, CHU Angers, Angers, France., Ku M; St Vincent's Private Hospital Melbourne, Melbourne, VIC, Australia., Rusconi C; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Khwaja J; University College London Hospitals NHS Foundation Trust, London, United Kingdom., Narkhede M; University of Alabama at Birmingham, Birmingham, AL., Lewis KL; Linear Clinical Research and Sir Charles Gairdner Hospital, Perth, WA, Australia., Calimeri T; IRCCS San Raffaele Scientific Institute, Milan, Italy., Durot E; Hôpital Robert Debré CHU de Reims, Reims, France., Renaud L; Hôpital Saint-Louis, AP-HP, Paris, France., Øvlisen AK; Aalborg University Hospital, Aalborg, Denmark., McIlroy G; University Hospitals Birmingham, Birmingham, United Kingdom., Ebsworth TJ; University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom., Elliot J; The Christie NHS Foundation Trust, Manchester, United Kingdom., Santarsieri A; Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom., Ricard L; Hospital Saint-Antoine AP-HP, Paris, France., Shah N; Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United Kingdom., Liu Q; Princess Margaret Cancer Centre, Toronto, ON, Canada., Zayac AS; Brown University and Lifespan Cancer Institute, Providence, RI., Vassallo F; Città della Salute e della Scienza di Torino, Torino, Italy., Lebras L; Centre Léon Bérard, Lyon, France., Roulin L; University Hospital Henri-Mondor AP-HP, Paris, France., Lombion N; Hopital Mignot Centre Hospitalier de Versailles, Versailles, France., Manos K; Austin Hospital, Melbourne, VIC, Australia., Fernandez R; Hospital de Cabueñes, Gijon, Spain., Hamad N; St Vincent's Hospital Sydney, Sydney, Australia., Lopez-Garcia A; Fundacion Jimenez Diaz University Hospital, Health Research Institute Instituto de Investigaciòn Sanitaria-Fundacion Jimenex Diaz (IIS-FJD), Madrid, Spain., O'Mahony D; Bon Secours Cork Cancer Centre, Cork, Ireland., Gounder P; Concord Clinical School, Concord Hospital University of Sydney, Sydney, NSW, Australia., Forgeard N; La Pitie Salpetriere Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP)-Sorbonne Universite, Paris, France., Lees C; Oxford University Hospitals NHS Trust, Churchill Cancer Center, Oxford, United Kingdom., Agbetiafa K; Institut Curie Hôpital René Huguenin, Saint-Cloud, France., Strüßmann T; Department of Medicine, University Medical Center Freiburg, Freiburg, Germany., Htut TW; Aberdeen Royal Infirmary, Aberdeen, United Kingdom., Clavert A; Service des Maladies du Sang, CHU Angers, Angers, France., Scott H; St Vincent's Private Hospital Melbourne, Melbourne, VIC, Australia., Guidetti A; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Barlow BR; University of Alabama at Birmingham, Birmingham, AL., Tchernonog E; CHU de Montpellier, Montpellier, France; and., Smith J; Liverpool University Hospitals Foundation Trust, Liverpool, United Kingdom., Miall F; University Hospitals of Leicester NHS Trust, Leicester, United Kingdom., Fox CP; Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom., Cheah CY; Linear Clinical Research and Sir Charles Gairdner Hospital, Perth, WA, Australia., El Galaly TC; Aalborg University Hospital, Aalborg, Denmark., Ferreri AJM; IRCCS San Raffaele Scientific Institute, Milan, Italy., Cwynarski K; University College London Hospitals NHS Foundation Trust, London, United Kingdom., McKay P; Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2022 Apr 21; Vol. 139 (16), pp. 2499-2511.
DOI:	10.1182/blood.2021014506
Abstrakt:	Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n = 749) or at the end (n = 635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.7%), with no difference between i-HD-MTX and EOT: 5.7% vs 5.8%, P = .98; 3-year difference: 0.04% (-2.0% to 3.1%). Conclusions were unchanged on adjusting for baseline prognostic factors or on 6-month landmark analysis (n = 1253). In patients with a high CNS international prognostic index (n = 600), the 3-year CNS relapse rate was 9.1%, with no difference between i-HD-MTX and EOT. On multivariable analysis, increasing age and renal/adrenal involvement were the only independent risk factors for CNS relapse. Concurrent intrathecal prophylaxis was not associated with a reduction in CNS relapse. R-CHOP delays of ≥7 days were significantly increased with i-HD-MTX vs EOT, with 308 of 1573 (19.6%) i-HD-MTX treatments resulting in a delay to subsequent R-CHOP (median 8 days). Increased risk of delay occurred in older patients when delivery was later than day 10 in the R-CHOP cycle. In summary, we found no evidence that EOT delivery increases CNS relapse risk vs i-HD-MTX. Findings in high-risk subgroups were unchanged. Rates of CNS relapse in this HD-MTX-treated cohort were similar to comparable cohorts receiving infrequent CNS prophylaxis. If HD-MTX is still considered for certain high-risk patients, delivery could be deferred until R-CHOP completion. (© 2022 by The American Society of Hematology.)
Databáze:	MEDLINE
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