Patient Perceptions of CAR-T Therapy in the USA: Findings from In-Depth Interviews.

INTRODUCTION: Chimeric antigen receptor-T cell (CAR-T) therapy has revolutionized advanced blood cancer treatment. However, preparation, administration, and recovery from these therapies can be complex and burdensome to patients and their care partners. Utilization of an outpatient setting for CAR-T therapy administration could help improve convenience and quality of life. METHODS: In-depth qualitative interviews were conducted with 18 patients in the USA with relapsed/refractory multiple myeloma or relapsed/refractory diffuse large B-cell lymphoma, 10 of whom had completed investigational or commercially approved CAR-T therapy and 8 of whom had discussed it with their physicians. We aimed to better understand inpatient experiences and patient expectations regarding CAR-T therapy and to ascertain patient perspectives on the possibility of outpatient care. RESULTS: CAR-T offers unique treatment benefits, particularly high response rates with an extended treatment-free period. All study participants completing CAR-T were very positive about their inpatient recovery experience. Most reported mild-to-moderate side effects; two experienced severe side effects. All said that they would opt to undergo CAR-T therapy again. Participants felt that the primary advantage of inpatient recovery was immediate access to care and on-going monitoring. Perceived advantages of the outpatient setting were comfort and familiarity. Because immediate access to care was seen as crucial, patients recovering in an outpatient setting would seek either a direct contact person or phone line for assistance if needed. CONCLUSION: As institutions become more experienced with CAR-T therapies, outpatient care may help reduce financial strain. Patient input can help institutions improve the outpatient experience and ensure safety and effectiveness of CAR-T programs.

Fetal cells in the murine maternal lung have well-defined characteristics and are preferentially located in alveolar septum.

The transfer of fetal cells to maternal organs occurs in mouse and human pregnancy. Techniques such as polymerase chain reaction and flow cytometry do not permit study of fetal cell morphology or anatomic location. Using a green fluorescent protein (GFP) transgenic mouse model, our objective was to determine whether GFP+ signal emanates from intact or degraded fetal cells, and whether they have a characteristic appearance and location within maternal lung. Four wild-type female mice were mated to males homozygous for the Gfp transgene and studied at days e16-18. Controls were 2 females mated to wild-type males. Morphologic appearance and anatomic position of each GFP+ object within maternal lung was recorded. GFP signals were sufficiently bright to be visualized without anti-GFP antibody and were confirmed by confocal microscopy to be separate from fluorescent artifact. Of 438 GFP+ objects detected, 375 (85.6%) were from intact cells, and 63 (14.4%) were acellular. Four distinct categories of intact cells were observed. Of these, 23.2% had mononuclear morphology with a relatively large nucleus and GFP+ cytoplasm (Group A). An additional group of cells (10.1%) had mononuclear morphology and podocyte extensions (Group B). The remainder of cells had fragmented nuclei or cytoplasm. Both intact cells and acellular fragments were predominantly localized to the maternal alveolar septum (P<0.0001). This study demonstrates that fetal GFP+ cells are predominantly located in the alveolar septum and have characteristic morphologies, although it remains unclear whether these represent distinct categories of cells or degrading cells. Nevertheless, this naturally acquired population of fetal cells in maternal lung should be considered in studies of lung biology and repair.

Maternal background strain influences fetal-maternal trafficking more than maternal immune competence in mice.

The objective of this study was to determine if fetal-maternal cell trafficking is affected by maternal immune competence and/or parental background strain using fluorescence-activated cell sorting (FACS). In our experience the sensitivity of FACS allows for the detection of 5 fetal in 10(7) maternal cells and assessment of cell surface phenotype. Wild-type C57BL/6J (n=18), FVB/NJ (n=15), and immunodeficient B6129S7-Rag1(tm1Mom)/J (n=16) female mice were mated to C57BL/6J males homozygous for the green fluorescent protein (GFP) transgene. Single cell suspensions of maternal lung, liver, spleen, bone marrow, and blood were analyzed between late gestation (day e16-18) and 1 day post-partum for the number of GFP-positive fetal cells in relation to 10(7) maternal cells and the percentage of GFP-positive cells that expressed the surface markers CD11b, CD29, CD34, CD44, or CD105. The highest relative proportions of GFP-positive fetal cells were observed in maternal lungs and livers from immunocompetent allogenic females. Among congenic matings, fetal cell microchimerism was higher in immunodeficient compared with immunocompetent females. Maternal strain and strain differences between the mother and father statistically significantly affected both the numbers of fetal cells and the relative distribution of cell types in maternal organs. The highest relative proportion of fetal cells was observed in allogenic matings with immunocompetent females. Since allogenic matings are more similar to those that occur in humans, future studies using animal models of microchimerism should consider incorporating this type of experimental design.

Fetal cell microchimerism and cancer: a nexus of reproduction, immunology, and tumor biology.

Fetal cell microchimerism (FCM) is the persistence of fetal cells in the maternal circulation and organs following pregnancy. Proposed hypotheses about the function of fetal cells in the pathogenesis of maternal cancer include promotion of tumorigenesis, protection by providing immunosurveillance, and participation in tissue repair. To date, studies of FCM and cancer have been primarily descriptive and quantitative. More research is needed to understand the cellular phenotype of the microchimeric cells in maternal tumors and whether they have a functional role. This research will require further study using a multidisciplinary approach, incorporating knowledge of the fetomaternal relationship, tumor biology, immunology, and clinical oncology.