Kosydar, Samuel R

SummaryIn individuals with high‐count monoclonal B‐cell lymphocytosis (MBL), we investigated if lymphadenopathy or splenomegaly found by imaging was associated with shorter time to first chronic lymphocytic leukaemia (CLL) therapy (TTFT) and overall survival (OS). Individuals with MBL seen at Mayo Clinic (2002–2019) were retrospectively divided into three cohorts based on imaging studies within 1 year of diagnosis: no imaging studies (Cohort A); imaging with no evidence of lymphadenopathy/splenomegaly (Cohort B); imaging with evidence of lymphadenopathy/splenomegaly (Cohort C). We compared baseline characteristics, TTFT and OS across the MBL cohorts to a cohort of individuals with small lymphocytic lymphoma (SLL). A total of 1078 patients were included: 640 with MBL and 438 with SLL. Compared to Cohort B, individuals in Cohort C were more likely to have unmutated immunoglobulin heavy chain variable region (IGHV) (43% vs. 25% p = 0.016), high‐risk fluorescence in situ hybridization (FISH) (del17p and del11q in 15% vs. 4%, p = 0.038) and higher expression of CD38 (31% vs. 16%; p = 0.011). After adjusting for sex and CLL‐International Prognostic Index (IPI), lymphadenopathy/splenomegaly was associated with a shorter TTFT (hazard ratio [HR] = 2.04, 95% confidence interval [CI]: 1.02–4.04, p = 0.042) but not OS (HR = 1.09, 95% CI: 0.62–1.92, p = 0.775). Lymphadenopathy/splenomegaly on imaging in individuals with high‐count MBL is associated with a more unfavourable risk profile and shorter time to first CLL‐directed therapy.

Abstract Background High-grade gliomas (HGG) have a poor prognosis despite aggressive treatment. Severe, persistent lymphopenia occurring in HGG patients after concurrent chemoradiation is associated with worse survival. NT-I7, a long-acting interleukin-7 analog, has been shown to increase CD4 and CD8 counts in healthy, septic, and HIV-positive adults. This multi-institutional, NCI-funded dose-escalation trial is the first to evaluate NT-I7 safety and activity in HGG patients with severe treatment-related lymphopenia (TRL) and the effect of co-administered glucocorticoids. Methods Eligible HGG patients had CD4 counts <300 cells/mm3 after 5 weeks of standard chemoradiation and were receiving either ≤0.75 or ≥4 mg/day of dexamethasone. Patients received a single intramuscular dose of NT-I7 (60 or 360 µg/kg) post-chemoradiation, followed by safety evaluation and multi-parameter, longitudinal monitoring of lymphocyte populations and immunologic function. Results NT-I7 was well tolerated in all 12 patients (median age 64; median CD4 count 161 cells/mm³) before the study closed prematurely. Absolute lymphocyte counts doubled in 83% (10/12; 95% CI: 51.6%-97.9%) of patients, and CD4 counts doubled in 42% (5/12; 95% CI: 15.2%-72.3%) of patients. Glucocorticoid use did not significantly affect CD4 or lymphocyte increases. Correlative immune profiling revealed increased Ki67 expression in CD4 (P < .005) and CD8 (P < .05) after one week, along with the expansion of CD4 and CD8 T-cell subsets and CD56 + natural killer cells. Conclusions NT-I7 is well tolerated and effectively increases lymphocyte and CD4 counts in severe TRL patients, regardless of glucocorticoid use, suggesting its potential to mitigate TRL and improve outcomes in HGG.