CD19+ lineage chimerism, an early biomarker after anti-CD19 CAR-T cell therapy in patients previously receiving a hematopoietic stem cell transplantation.

Treatment targeting CD19 by a chimeric antigen receptor expressed on T cells (anti-CD19 CAR-T) has led to a breakthrough in the management and treatment of relapsed and refractory B- cell acute lymphoblastic leukemia (B-ALL). After infusion, the efficacy of anti-CD19 CAR-T is monitored by bone marrow negative minimal residual disease and the absence of peripheral CD19+ B lymphocytes (B-cell aplasia). In patients who have received an allogenic Hematopoietic Stem Cell Transplantation (HSCT) prior to treatment with anti-CD19 CAR-T, monitoring lineage-specific chimerism could be helpful. We found that on 4 patients who received anti-CD19 CAR-T cells after HSCT and achieved early complete response, CD19+ lineage mixed chimerism but not CD3+ lineage mixed chimerism monitored by molecular techniques anticipated earlier than B-cell aplasia determined by flow cytometry, lack of effectiveness of anti-CD19 CAR-T and leukemia relapse. Donor lymphocyte infusions (DLIs) did not prevent relapse but recovered CD3+ full donor chimerism. We suggest that continuous lineage chimerism analysis should be done routinely in patients who receive anti-CD19 CAR-T cells after HSCT and achieve complete remission because it can support early treatment intervention. However, the role of DLI in this setting is unclear, so further prospective studies should be developed.

Outcome of Severe Bacterial Pneumonia in the Era of Pneumococcal Vaccination.

Introduction: After the introduction of pneumococcal conjugate vaccines, community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae has decreased whereas Staphylococcus aureus and Streptococcus pyogenes could be increasing. These bacteria have been associated with high rates of complications. Aims: (1) To describe the characteristics of pediatric bacterial CAP requiring hospitalization. (2) To compare outcomes according to causative microorganisms. (3) To analyze changes in bacterial CAP rate and etiology over time. Patients and Methods: Retrospective single-center study of inpatients aged 1 month-16 years with culture-confirmed bacterial CAP in 2010-2018 in Madrid, Spain. Results: We included 64 cases (42 S. pneumoniae, 13 S. pyogenes and 9 S. aureus). Culture-confirmed CAP represented 1.48-2.33/1,000 all-cause pediatric hospital admissions, and its rate did not vary over time. However, there was a significant decrease in pneumococcal CAP in the last 3 years of the study (78% of CAP in 2010-2015 vs. 48% in 2016-18, p = 0.017). Median hospital stay was 10.5 days (interquartile range 5-19.5), 38 patients (59%) developed complications and 28 (44%) were admitted to the intensive care unit. Outcomes were similar among children with S. pneumoniae and S. aureus CAP, whereas S. pyogenes was associated with a higher risk for complications (OR 8 [95%CI 1.1-57.2]) and ICU admission (OR 7.1 [95%CI 1.7-29.1]) compared with pneumococcal CAP. Conclusion: In a setting with high PCV coverage, culture-confirmed bacterial CAP did not decrease over time and there was a relative increase of S. pyogenes and S. aureus. Children with CAP caused by S. pyogenes were more likely to develop complications.