RESUMO
BACKGROUND: Adoptive immunotherapy using CD19-targeted Chimeric antigen receptor T cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Data is limited on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy. METHODS: We conducted a retrospective study including 19 patients who received axicabtagene ciloleucel and investigated associations between cytopenia and infectious complications after D30. RESULTS: Nineteen patients were included, consisting of 42% Hispanic, 32% Caucasian, 21% African-American, and 5% Asian subjects. Post-D30 of CAR-T infusion, 47% patients (n=9) developed an infection and 53% (n=10) remained infection-free. The most common infection type observed was viral (7 patients) followed by bacterial (5 patients) and fungal (3 patients). Of 25 total infectious events, 56% were grade 1 or 2 and 44% were grade 3 with 10 being viral in etiology. To determine the kinetics of lymphohematopoietic reconstitution and its association with infection risk, we evaluated the relationship between cytopenias and rates of infection after D30. Notably, compared to non-infection group, infection group had a higher median absolute lymphocyte count (ALC) (1,000/µL vs. 600/µL, P<0.05), a lower median absolute neutrophil count (ANC)/ALC ratio (1.6 vs. 3.1, P<0.05) and a lower median AMC/ALC at D30 (0.37 vs. 1.67, P<0.05). In addition, we observed that only 22% of patients had recovered ANC >1,500/µL in the infection group as opposed to 70% in the non-infection group at D90 (P<0.05). Fifty-eight percent of the patients (11/19) with relapsed refractory DLBCL achieved a complete response with a median follow-up of 233 days (7.7 months). CONCLUSIONS: Although CAR-T cell therapy is highly effective, infectious complications remain an important cause of morbidity and mortality. Low ANC/ALC and AMC/ALC ratios at D30 are potential novel predictors of infection and can be considered in future prophylactic strategies.
RESUMO
PURPOSE: Delays in initiating elective inpatient chemotherapy can decrease patient satisfaction and increase length of stay. At our institution, we observed that 86% of patients who were admitted for elective chemotherapy experienced a delay-more than 6 hours-with a median time to chemotherapy of 18.9 hours. We developed a process improvement initiative to improve time to chemotherapy for elective chemotherapy admissions. METHODS: Our outcome measure was the time from admission to chemotherapy administration in patients who were admitted for elective chemotherapy. Process measures were identified and monitored. We collected baseline data and used performance improvement tools to identify key drivers. We focused on these key drivers to develop multiple plan-do-study-act cycles to improve our outcome measure. Once we started an intervention, we collected data every 2 weeks to assess our intervention. RESULTS: At the time of interim analysis, we observed a median decrease in time to chemotherapy administration from 18.9 hours to 8.85 hours (P = .005). Median time to laboratory results resulted decreased from 3.17 hours to 0.00 hours. There was no change in time from signing chemotherapy to nurse releasing the chemotherapy. We noted that more providers were signing the chemotherapy before patient admission. CONCLUSION: By implementing new admission workflows, optimizing our use of the electronic medical record to communicate among providers, and improving preadmission planning we were able to reduce our median time to chemotherapy for elective admissions by 53.2%. Improvement is still needed to meet our goals and to ensure the sustainability of these ongoing efforts.
