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.

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., Balotis, C., Kennedy, B., Wagner, S., Dyer, M. J. S., Smith, D., McMillan, A. K., Miall, F., Bishton, M., & 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