Impact of Previous Allogeneic Hematopoietic Stem Cell Transplantation on Chimeric Antigen Receptor (CAR) T Cell Treatment for Relapsed/Refractory Multiple Myeloma.

BACKGROUND: Anti-BCMA-directed chimeric antigen receptor (CAR) T cells are effective treatment for patients with refractory/relapsed multiple myeloma (RRMM). However, little is known about the impact of previous allogeneic hematopoietic stem cell transplantation (allo-HSCT) on lymphocyte collection for production of CAR T cells and subsequent treatment with CAR T cells. PATIENTS AND METHODS: We performed a retrospective analysis of cellular composition of lymphocyte collections, CAR T cell expansion and treatment outcomes of RRMM patients undergoing therapy with idecabtagene vicleucel (ide-cel) with and without history of allo-HSCT. 27 patients (11/27 female) with median age 63 (range 39-75) years were analyzed. Five patients (19%) had the history of allo-HSCT median of 5.5 years before ide-cel. RESULTS: Prior to apheresis, the white blood cell, absolute lymphocyte counts, CD3+ cells and monocytes did not differ in patients with and without prior allo-HSCT. We also noticed no differences in the collected CD3+ yields or cellular compositions of lymphocyte collections. One year after ide-cel infusion, the progression-free survival and overall survival of patients with and without previous allo-HSCT did not differ with 60% and 45% respectively (P = .58) and 66.7% and 74% respectively (P = .84). The highest expansion of CAR T was detected between day 7 after infusion and showed no difference regarding previous allo-HSCT (P = .71). No graft-versus-host disease during the follow-up was detected. CONCLUSION: Our data confirm that the treatment with ide-cel is feasible for patients with prior allo-HSCT. Furthermore, allo-HSCT did not influence cellular composition of lymphocyte collections, clinical outcome or in vivo expansion of ide-cel.

Gender Role, Gender Identity and Sexual Orientation in CAIS ("XY-Women") Compared With Subfertile and Infertile 46,XX Women.

The perception of gender development of individuals with complete androgen insensitivity syndrome (CAIS) as unambiguously female has recently been challenged in both qualitative data and case reports of male gender identity. The aim of the mixed-method study presented was to examine the self-perception of CAIS individuals regarding different aspects of gender and to identify commonalities and differences in comparison with subfertile and infertile XX-chromosomal women with diagnoses of Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) and polycystic ovary syndrome (PCOS). The study sample comprised 11 participants with CAIS, 49 with MRKHS, and 55 with PCOS. Gender identity was assessed by means of a multidimensional instrument, which showed significant differences between the CAIS group and the XX-chromosomal women. Other-than-female gender roles and neither-female-nor-male sexes/genders were reported only by individuals with CAIS. The percentage with a not exclusively androphile sexual orientation was unexceptionally high in the CAIS group compared to the prevalence in "normative" women and the clinical groups. The findings support the assumption made by Meyer-Bahlburg ( 2010 ) that gender outcome in people with CAIS is more variable than generally stated. Parents and professionals should thus be open to courses of gender development other than typically female in individuals with CAIS.

Hippocampal structure, metabolism, and inflammatory response after a 6-week intense aerobic exercise in healthy young adults: a controlled trial.

Interventional studies suggest that changes in physical fitness affect brain function and structure. We studied the influence of high intensity physical exercise on hippocampal volume and metabolism in 17 young healthy male adults during a 6-week exercise program compared with matched controls. We further aimed to relate these changes to hypothesized changes in exercised-induced brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). We show profound improvement of physical fitness in most subjects and a positive correlation between the degree of fitness improvement and increased BDNF levels. We unexpectedly observed an average volume decrease of about 2%, which was restricted to right hippocampal subfields CA2/3, subiculum, and dentate gyrus and which correlated with fitness improvement and increased BDNF levels negatively. This result indicates that mainly those subjects who did not benefit from the exercise program show decreased hippocampal volume, reduced BDNF levels, and increased TNF-α concentrations. While spectroscopy results do not indicate any neuronal loss (unchanged N-acetylaspartate levels) decreased glutamate-glutamine levels were observed in the right anterior hippocampus in the exercise group only. Responder characteristics need to be studied in more detail. Our results point to an important role of the inflammatory response after exercise on changes in hippocampal structure.

[A questionnaire for the assessment of women's perception of their own femininity: a study on women with Mayer-Rokitansky-Kuster-Hauser-syndrome and women with polycystic ovary syndrome]. / Fragebogen zum Erleben der eigenen Weiblichkeit (FB-W): Ergebnisse von Frauen mit Mayer-Rokitansky-Küster-Hauser Syndrom und Frauen mit polyzystischem Ovarsyndrom.

Women with Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS) or polycystic ovary syndrome (PCOS) experience substantial changes in female body characteristics. It was investigated how this is associated with changes concerning the experience of one's own femininity. A questionnaire was developed to measure the experience of one's own femininity. The question-naire assesses how important several aspects are to women for their experience of their own femininity. Data from 49 women with MRKHS and 55 women with PCOS were compared to a non-clinical sample (932 women). The experience of their own femininity differed between the clinical groups as well as in comparison to the control sample. Diagnosis-specific characteristics emerged, which should be considered in the treatment of affected women. The developed questionnaire proved to be suitable for measuring differences in the experience of one's own femininity between groups of gynecological -patients.

Sexual quality of life of individuals with 46,XY disorders of sex development.

INTRODUCTION: There has recently been a growing acceptance that it is not only heterosexual functioning of surgically adjusted genitalia which should be considered when measuring the treatment outcome of persons with disorders of sex development (DSD) but also their overall sexual quality of life (SexQoL). AIM: A comprehensive cross-sectional investigation of SexQoL of persons with 46,XY DSD. METHODS: Forty-seven persons with 46,XY DSD (age 17-60 years) were examined by means of a questionnaire on various aspects of SexQoL. Scores were compared to a nonclinical convenience sample consisting of 145 women. Data were analyzed separately for diagnostic subgroups. Furthermore, persons whose external genitalia had been surgically corrected were compared with persons whose genitalia had been left unaltered. MAIN OUTCOME MEASURES: The Multidimensional Scale of Sexuality, the German Questionnaire on Feelings of Inadequacy in Social and Sexual Situations (FUSS), items on sexual dysfunctions according to DSM-IV-TR and self-constructed measures on sexual-activity history (e.g., previous sexual experience), sexual anxieties, and satisfaction with overall sex life and sexual function comprised the standardized assessment instruments. RESULTS: Compared with the nonclinical group, persons with 46,XY DSD had more often no partner (P = 0.056), felt more insecure in social (Mdn(DSD) = 17.0, Mdn(comparison) = 12.0, P = 0.001) and sexual situations (Mdn(DSD) = 17.0, Mdn(comparison) = 11.0, P = 0.006), had more sexual problems (Mdn(DSD) = 4.0, Mdn(comparison) = 3.0, P = 0.001), and were less satisfied with overall sex life (Mdn(DSD) = 3.0, Mdn(comparison) = 4.0, P = 0.000) and sexual function (Mdn(DSD) = 4.0, Mdn(comparison) = 4.0, P = 0.000). Results were inconsistent with regard to sexual-activity history (e.g., previous sexual experience). Participants who underwent genital surgery showed less dyspareunia (P = 0.027) but more fear of injuries during intercourse (P = 0.019) than those whose genitals were left unaltered. CONCLUSIONS: SexQoL of persons with 46,XY DSD may be impaired. Differences in SexQoL between diagnostic subgroups, effect of corrective genital surgery, and the influence of gender assignment will have to be further investigated in future studies.