Hematopoiesis and immune reconstitution after CD19 directed chimeric antigen receptor T-cells (CAR-T): A comprehensive review on incidence, risk factors and current management.

Impaired function of hematopoiesis after treatment with chimeric antigen T-cells (CAR-T) is a frequent finding and can interest a wide range of patients, regardless of age and underlying disease. Trilinear cytopenias, as well as hypogammaglobulinemia, B-cell aplasia, and T-cell impairment, can severely affect the infectious risk of CAR-T recipients, as well as their quality of life. In this review, we provide an overview of defects in hematopoiesis after CAR-T, starting with a summary of different definitions and thresholds. We then move to summarize the main pathogenetic mechanisms of cytopenias, and we offer insight into cytomorphological aspects, the role of clonal hematopoiesis, and the risk of secondary myeloid malignancies. Subsequently, we expose the major findings and reports on T-cell and B-cell quantitative and functional impairment after CAR-T. Finally, we provide an overview of current recommendations and leading experiences regarding the management of cytopenias and defective B- and T-cell function.

Gender and ethnic differences in rates of immune reconstitution, AIDS diagnosis, and survival.

In this work, we use 2011-2013 Texas HIV surveillance data (N=2,175) and apply hierarchical linear and Cox regression modeling to characterize the association of gender and race/ethnicity with rate of immune recovery and determine whether immune recovery contributes to gender and racial/ethnic disparities in AIDS diagnosis and survival. The associations between gender and rate of immune recovery and between race/ethnicity and rate of immune recovery were not statistically significant (p > 0.05). In the multivariate survival analyses, there was no statistically significant association between gender and AIDS diagnosis (Adjusted Hazard Ratio (AHR) = 1.06, p = 0.61, 95%=0.85-1.32) and between race/ethnicity and AIDS diagnosis (Blacks vs Whites: AHR = 1.10, p = 0.24, 95% CI = 0.94-1.30; Hispanics vs Whites: AHR = 1.06, p = 0.46, 95% CI = 0.91-1.24). Similarly, there were no statistically significant associations with death (males vs females: AHR = 0.88, p = 0.73, 95% CI = 0.43-1.81; Blacks vs Whites: AHR = 0.68 p = 0.25, 95% CI = 0.36-1.30; Hispanics vs Whites: AHR = 0.96, p = 0.88, 95% CI = 0.55-1.67). However, the direction of the point estimates were in the reverse direction when compared to the rate of immune recovery or the AIDS diagnosis models. Our findings suggest that differences in rate of immune recovery may better explain disparities in AIDS diagnosis than disparities in survival. Future studies with longer follow-up may potentially generate statistically significant results.

Mass Cytometry for the Assessment of Immune Reconstitution After Hematopoietic Stem Cell Transplantation.

Mass cytometry, or Cytometry by Time-Of-Flight, is a powerful new platform for high-dimensional single-cell analysis of the immune system. It enables the simultaneous measurement of over 40 markers on individual cells through the use of monoclonal antibodies conjugated to rare-earth heavy-metal isotopes. In contrast to the fluorochromes used in conventional flow cytometry, metal isotopes display minimal signal overlap when resolved by single-cell mass spectrometry. This review focuses on the potential of mass cytometry as a novel technology for studying immune reconstitution in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Reconstitution of a healthy donor-derived immune system after HSCT involves the coordinated regeneration of innate and adaptive immune cell subsets in the recipient. Mass cytometry presents an opportunity to investigate immune reconstitution post-HSCT from a systems-level perspective, by allowing the phenotypic and functional features of multiple cell populations to be assessed simultaneously. This review explores the current knowledge of immune reconstitution in HSCT recipients and highlights recent mass cytometry studies contributing to the field.