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Kinetics of T-cell subset reconstitution following treatment with bendamustine and rituximab for low-grade lymphoproliferative disease: a population-based analysis

Martínez-Calle, Nicolás; Hartley, Sarah; Ahearne, Matthew; Kasenda, Benjamin; Beech, Amy; Knight, Helen; Balotis, Constantine; Kennedy, Ben; Wagner, Simon; Dyer, Martin J. S.; Smith, Dean; McMillan, Andrew K.; Miall, Fiona; Bishton, Mark; Fox, Christopher P.

Authors

Nicolás Martínez-Calle

Sarah Hartley

Matthew Ahearne

Benjamin Kasenda

Amy Beech

Helen Knight

Constantine Balotis

Ben Kennedy

Simon Wagner

Martin J. S. Dyer

DEAN SMITH Dean.Smith@nottingham.ac.uk
Clinical Associate Professor in Haematology

Andrew K. McMillan

Fiona Miall

Mark Bishton

Christopher P. Fox



Abstract

Delayed lymphocyte and T-cell immune reconstitution following bendamustine-rituximab (BR) for indolent non-Hodgkin lymphoma (iNHL) has been described, but no information is available for chronic lymphocytic leukaemia (CLL). We present a population-based retrospective analysis of immune reconstitution and risk of infection following BR. Outcomes included timing/correlates of CD4+ recovery and risk of ≥grade 3 infections. Consecutively treated patients (1 April 2014 to 31 January 2017) were included (n=295),with a median age of 65years (range 33–92); 57% were 1st line treatments. Median cumulative bendamustine dose was 1080mg/m 2 (range 140–1440mg/m 2 ). CD4/CD8/CD19/NK subsets were available for 148 patients. Median follow-up was 24months. Median times to lymphocyte count (ALC) recovery (≥1×10 9 /l) and CD4+ recovery (≥0·2×10 9 /l) were 26 and 24months, respectively. Bendamustine total dose >1080mg/m 2 (hazard ratio [HR] 0·4; 95% confidence interval [CI]: 0·2–0·8), end-of-treatment ALC ≤0·4×10 9 /l (HR 0·53; 95% CI: 0·3–0·9) and CD4+ <0·1×10 9 /l 1-year post-BR (HR 0·03; 95% CI: 0·008–0·15) were covariables for delayed CD4+ recovery. ALC-recovery ≥1×10 9 /l was an unreliable predictor of CD4+ recovery (negative predictive vale 74%, positive predictive value 86%, likelihood ratio 3·3). CD4+ lymphopenia >3years was a significant risk factor for ≥grade 3 infections (Odds ratio 3·4; 95% CI: 1·4–6·9). CD4+ recovery after BR is unexpectedly delayed and late recovery is associated with risk of serious infections. Monitoring CD4+ following BR could identify patients at high risk of delayed infections.

Citation

Martínez-Calle, N., Hartley, S., Ahearne, M., Kasenda, B., Beech, A., Knight, H., …Fox, C. P. (2019). Kinetics of T-cell subset reconstitution following treatment with bendamustine and rituximab for low-grade lymphoproliferative disease: a population-based analysis. British Journal of Haematology, 184(6), 957-968. https://doi.org/10.1111/bjh.15722

Journal Article Type Article
Acceptance Date Nov 5, 2018
Online Publication Date Dec 13, 2018
Publication Date Mar 1, 2019
Deposit Date Dec 15, 2022
Journal British Journal of Haematology
Print ISSN 0007-1048
Electronic ISSN 1365-2141
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 184
Issue 6
Pages 957-968
DOI https://doi.org/10.1111/bjh.15722
Keywords Hematology
Public URL https://nottingham-repository.worktribe.com/output/14322705
Publisher URL https://onlinelibrary.wiley.com/doi/10.1111/bjh.15722