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

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 65 years (range 33-92); 57% were 1st line treatments. Median cumulative bendamustine dose was 1080 mg/m(2) (range 140-1440 mg/m(2)). CD4/CD8/CD19/NK subsets were available for 148 patients. Median follow-up was 24 months. Median times to lymphocyte count (ALC) recovery (>= 1 x 10(9)/l) and CD4+ recovery (>= 0 center dot 2 x 10(9)/l) were 26 and 24 months, respectively. Bendamustine total dose >1080 mg/m(2) (hazard ratio [HR] 0 center dot 4; 95% confidence interval [CI]: 0 center dot 2-0 center dot 8), end-of-treatment ALC <= 0 center dot 4 x 10(9)/l (HR 0 center dot 53; 95% CI: 0 center dot 3-0 center dot 9) and CD4+ BR (HR 0 center dot 03; 95% CI: 0 center dot 008-0 center dot 15) were covariables for delayed CD4+ recovery. ALC-recovery >= 1 x 10(9)/l was an unreliable predictor of CD4+ recovery (negative predictive vale 74%, positive predictive value 86%, likelihood ratio 3 center dot 3). CD4+ lymphopenia >3 years was a significant risk factor for >= grade 3 infections (Odds ratio 3 center dot 4; 95% CI: 1 center dot 4-6 center dot 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.