The use of posttransplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis has revolutionized haploidentical hematopoietic stem cell transplantation (HSCT), allowing safe infusion of unmanipulated T cell-replete grafts. PT-Cy selectively eliminates proliferating alloreactive T cells, but whether and how it affects natural killer (NK) cells and their alloreactivity is largely unknown. Here we characterized NK cell dynamics in 17 patients who received unmanipulated haploidentical grafts, containing high numbers of mature NK cells, according to PT-Cy-based protocols in 2 independent centers. In both series, we documented robust proliferation of donor-derived NK cells immediately after HSCT. After infusion of Cy, a marked reduction of proliferating NK cells was evident, suggesting selective purging of dividing cells. Supporting this hypothesis, proliferating NK cells did not express aldehyde dehydrogenase and were killed by Cy in vitro. After ablation of mature NK cells, starting from day 15 after HSCT and favored by the high levels of interleukin-15 present in patients' sera, immature NK cells (CD62LNKG2AKIR) became highly prevalent, possibly directly stemming from infused hematopoietic stem cells. Importantly, also putatively alloreactive single KIR NK cells were eliminated by PT-Cy and were thus decreased in numbers and antileukemic potential at day 30 after HSCT. As a consequence, in an extended series of 99 haplo-HSCT with PT-Cy, we found no significant difference in progression-free survival between patients with or without predicted NK alloreactivity (42% vs 52% at 1 year, = NS). Our data suggest that the majority of mature NK cells infused with unmanipulated grafts are lost upon PT-Cy administration, blunting NK cell alloreactivity in this transplantation setting.
On March 10, 2020, Italy went into lockdown due to the Coronavirus Disease-19 (COVID-19) pandemic. The World Health Organization highlighted how the lockdown had negative consequences on psychological well-being, especially for children. The present study aimed to investigate parental correlates of children’s emotion regulation during the COVID-19 lockdown. Within the Social Cognitive Theory framework, a path model in which parenting self-efficacy and parental regulatory emotional self-efficacy mediated the relationship between parents’ psychological distress and both children’s emotional regulation, and children’s lability/negativity, was investigated. A total of 277 parents of children aged from 6 to 13 years completed an online survey that assessed their psychological distress, regulatory emotional self-efficacy, and parenting self-efficacy. Parents reported also children’s emotional regulation and lability/negativity. A structural equation model (SEM) using MPLUS 8.3 was tested. Results showed that the hypothesized model exhibited excellent fit, chi-square (83) = 140.40, p < 0.01, RMSEA = 0.05, CFI = 0.97, TLI = 0.96, SRMR = 0.04. The influences of parents’ psychological distress and parents’ regulatory emotional self-efficacy on children’s emotional regulation and lability/negativity were mediated by parenting self-efficacy. The mediation model was invariant across children’s biological sex and age, and geographical residence area (high risk vs. low risk for COVID-19). Results suggested how parents’ beliefs to be competent in managing parental tasks might be a protective factor for their children’s emotional well-being. Implications for intervention programs are discussed.
Haploidentical hematopoietic stem cell transplantation (HSCT) performed using bone marrow (BM) grafts and post-transplantation cyclophosphamide (PTCy) has gained much interest for the excellent toxicity profile after both reduced-intensity and myeloablative conditioning. We investigated, in a cohort of 40 high-risk hematological patients, the feasibility of peripheral blood stem cells grafts after a treosulfan-melphalan myeloablative conditioning, followed by a PTCy and sirolimus-based graft-versus-host disease (GVHD) prophylaxis (Sir-PTCy). Donor engraftment occurred in all patients, with full donor chimerism achieved by day 30. Post-HSCT recovery of lymphocyte subsets was broad and fast, with a median time to CD4 > 200/μL of 41 days. Cumulative incidences of grade II to IV and III-IV acute GVHD were 15% and 7.5%, respectively, and were associated with a significant early increase in circulating regulatory T cells at day 15 after HSCT, with values < 5% being predictive of subsequent GVHD occurrence. The 1-year cumulative incidence of chronic GVHD was 20%. Nonrelapse mortality (NRM) at 100 days and 1 year were 12% and 17%, respectively. With a median follow-up for living patients of 15 months, the estimated 1-year overall and disease-free survival (DFS) was 56% and 48%, respectively. Outcomes were more favorable in patients who underwent transplantation in complete remission (1-year DFS 71%) versus patients who underwent transplantation with active disease (DFS, 34%; P = .01). Overall, myeloablative haploidentical HSCT with peripheral blood stem cells (PBSC) and Sir-PTCy is a feasible treatment option: the low rates of GVHD and NRM as well as the favorable immune reconstitution profile pave the way for a prospective comparative trial comparing BM and PBSC in this specific transplantation setting.
Secure attachment relationships have been described as having a regulatory function in regard to children's emotions, social cognition, and behavior. Although some theorists and researchers have argued that attachment affects children's self-regulation, most attachment theorists have not strongly emphasized this association. The goal of the current meta-analysis was to determine the magnitude of the relation between attachment security status and effortful control (EC)/top-down self-regulation in children up to 18 years of age. One hundred six papers met the inclusion criteria and 101 independent samples were used in analyses. When secure attachment status was compared with insecure attachment status, a significant relation (effect size [ES]) with EC favoring children with a secure attachment was found (100 studies; 20,350 participants; r = .20). A stronger relation was found when the same coder evaluated attachment than when the coder was different and when the measure of attachment was continuous; other moderators were not significant. Securely attached children were higher in EC than their avoidant (r = .10) or resistant (r = .17) counterparts. Children with organized attachments were higher in EC than those with disorganized attachments (r = .17), although this finding could be due to publication bias. For some comparisons of subgroups (B vs. A, B vs. C, and/or D vs. all others), moderation was found by source of information (higher ES for same reporter), age at assessment of EC and/or attachment (higher ES at older ages), method of attachment (lower ES for observational measures), time difference between assessments or research design (higher ESs for smaller time differences and concurrent findings), and published versus unpublished studies (higher ES for unpublished studies for A vs. B). (PsycINFO Database Record
The hematopoietic cell transplantation specific comorbidity index (HCT-CI) has been developed to identify patients at high risk of mortality after an allograft. Reduced-intensity/ non-myeloablative regimens have decreased the non-relapse mortality (NRM) in elderly and/or heavily pretreated patients. We performed a retrospective study to assess whether HCT-CI may predict clinical outcomes in a cohort of 203 patients with nonHodgkin's (NHL; n ¼ 108), Hodgkin's lymphomas (HL; n ¼ 26), and multiple myeloma (MM; n ¼ 69), who were transplanted from a human leucocyte antigen (HLA)-matched sibling (n ¼ 121) or an unrelated donor (n ¼ 82) after a reduced-intensity regimen (n ¼ 154) or a low-dose total body irradiation-based non-myeloblative regimen (n ¼ 49). Cumulative incidence of NRM was 5, 16 and 20% at 1 year and 6, 24 and 27% at 2 years, for patients with an HCT-CI of 0, 1-2 and X3, respectively. By multivariate analysis, HCT-CI significantly predicted NRM (hazard ratio (HR) ¼ 1.6, P ¼ 0.03), overall survival (OS; HR ¼ 1.62, Po0.001) and progression-free survival (PFS; HR ¼ 1.43, P ¼ 0.002). Moreover, the Karnofsky performance status was also significantly associated with OS and NRM (HR ¼ 1.62, Po0.001 and HR ¼ 2.12, P ¼ 0.04, respectively). Conditioning type did not affect outcome after stratifying patients by HCT-CI. In the light of our study, all future prospective trials of the Gruppo Italiano Trapianti di Midollo (GITMO) will include the HCT-CI to stratify patients.
Sexting motivations during adolescence are related to developmental dimensions-such as sexual identity and body-image development-or harmful intentions-such as aggression among peers and partners. Sociocultural and media models can affect explorations of sexuality and redefinitions of body image, which in turn are related to sexting behaviors and motivations. In this study, we investigated the roles of body-esteem attribution, the internalization of media models, and body objectification as predictors of three sexting motivations: sexual purposes, body-image reinforcement, and instrumental/aggravated reasons. The participants were 190 Italian adolescents aged from 13 to 20 years old (M age = 17.4, SD age = 1.8; 44.7% females). Sexual purposes were predicted by body-esteem attribution and body objectification; body-image reinforcement was predicted by the internalization of media models, and instrumental/aggravated reasons were not predicted by any variable. Thus, only sexual purposes and body-image reinforcement appeared to be affected by body-image concerns due to media models.
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