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Blood advances
08 11, 2020;4 (15): 3586-3593.

Timing of high-dose methotrexate CNS prophylaxis in DLBCL: an analysis of toxicity and impact on R-CHOP delivery.

Matthew R Wilson, Toby A Eyre, Nicolas Martinez-Calle, Matthew Ahearne, Katrina E Parsons, Gavin Preston, Jahanzaib Khwaja, Jeremy Schofield, Johnathon Elliot, Almurtadha Mula Kh, Nimish Shah, Cheuk-Kie Cheung, Matthew A Timmins, Thomas Creasey, Kim Linton, Jeffery Smith, Christopher P Fox, Fiona Miall, Kate Cwynarski, Pamela McKay
Author Information
  1. Matthew R Wilson: Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
  2. Toby A Eyre: Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
  3. Nicolas Martinez-Calle: Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.
  4. Matthew Ahearne: University Hospitals of Leicester NHS Trust, Leicester, United Kingdom.
  5. Katrina E Parsons: Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
  6. Gavin Preston: Aberdeen Royal Infirmary, Aberdeen, United Kingdom.
  7. Jahanzaib Khwaja: University College Hospital, London, United Kingdom.
  8. Jeremy Schofield: Liverpool University Hospitals Foundation Trust, Liverpool, United Kingdom.
  9. Johnathon Elliot: Christie Hospital, Manchester, United Kingdom.
  10. Almurtadha Mula Kh: University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
  11. Nimish Shah: Norfolk and Norwich University Hospitals, Norwich, United Kingdom.
  12. Cheuk-Kie Cheung: Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
  13. Matthew A Timmins: University Hospitals of Leicester NHS Trust, Leicester, United Kingdom.
  14. Thomas Creasey: Freeman Hospital, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle, United Kingdom; and.
  15. Kim Linton: Christie Hospital, Manchester, United Kingdom.
  16. Jeffery Smith: Liverpool University Hospitals Foundation Trust, Liverpool, United Kingdom.
  17. Christopher P Fox: Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.
  18. Fiona Miall: University Hospitals of Leicester NHS Trust, Leicester, United Kingdom.
  19. Kate Cwynarski: University College Hospital, London, United Kingdom.
  20. Pamela McKay: Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
PMID: 32761231 DOI: 10.1182/bloodadvances.2020002421

Abstract

High-dose methotrexate (HD-MTX) is increasingly used as prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) at high risk of central nervous system (CNS) relapse. However, there is limited evidence to guide whether to intercalate HD-MTX (i-HD-MTX) between R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone given at 21-day intervals) or to give it at the end of treatment (EOT) with R-CHOP-21. We conducted a retrospective, multicenter analysis of 334 patients with DLBCL who received CNS prophylaxis with i-HD-MTX (n = 204) or EOT HD-MTX (n = 130). Primary end points were R-CHOP delay rates and HD-MTX toxicity. Secondary end points were CNS relapse rate, progression-free survival, and overall survival. The EOT group had more patients with a high CNS international prognostic index (58% vs 39%; P < .001) and more concurrent intrathecal prophylaxis (56% vs 34%; P < .001). Of the 409 cycles of i-HD-MTX given, 82 (20%) were associated with a delay of next R-CHOP (median, 7 days). Delays were significantly increased when i-HD-MTX was given after day 9 post-R-CHOP (26% vs 16%; P = .01). On multivariable analysis, i-HD-MTX was independently associated with increased R-CHOP delays. Increased mucositis, febrile neutropenia, and longer median inpatient stay were recorded with i-HD-MTX delivery. Three-year cumulative CNS relapse incidence was 5.9%, with no differences between groups. There was no difference in survival between groups. We report increased toxicity and R-CHOP delay with i-HD-MTX compared with EOT delivery but no difference in CNS relapse or survival. Decisions on HD-MTX timing should be individualized and, where i-HD-MTX is favored, we recommend scheduling before day 10 of R-CHOP cycles.

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MeSH Term

Antineoplastic Combined Chemotherapy Protocols
Central Nervous System Neoplasms
Cyclophosphamide
Doxorubicin
Humans
Lymphoma, Large B-Cell, Diffuse
Methotrexate
Neoplasm Recurrence, Local
Retrospective Studies
Rituximab
Vincristine

Chemicals

Rituximab
Vincristine
Doxorubicin
Cyclophosphamide
Methotrexate
Journal Article Multicenter Study Research Support, Non-U.S. Gov't
Article has an altmetric score of 12

Word Cloud

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