Immune modulation properties of zoledronic acid on TcRγδ T-lymphocytes after TcRαβ/CD19-depleted haploidentical stem cell transplantation: an analysis on 46 pediatric patients affected by acute leukemia

TcRαβ/CD19-cell depleted HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) represents a promising new platform for children affected by acute leukemia in need of an allograft and lacking a matched donor, disease recurrence being the main cause of treatment failure. The use of zoledronic acid to enhance TcRγδ+ lymphocyte function after TcRαβ/CD19-cell depleted haplo-HSCT was tested in an open-label, feasibility, proof-of-principle study. Forty-six children affected by high-risk acute leukemia underwent haplo-HSCT after removal of TcRαβ+ and CD19+ B lymphocytes. No post-transplant pharmacological graft-versus-host disease (GvHD) prophylaxis was given. Zoledronic acid was administered monthly at a dose of 0.05 mg/kg/dose (maximum dose 4 mg), starting from day +20 after transplantation. A total of 139 infusions were administered, with a mean of 3 infusions per patient. No severe adverse event was observed. Common side effects were represented by asymptomatic hypocalcemia and acute phase reactions (including fever, chills, malaise, and/or arthralgia) within 24–48 h from zoledronic acid infusion. The cumulative incidence of acute and chronic GvHD was 17.3% (all grade I-II) and 4.8% (all limited), respectively. Patients given 3 or more infusions of zoledronic acid had a lower incidence of both acute GvHD (8.8 vs. 41.6%, p = 0.015) and chronic GvHD (0 vs. 22.2%, p = 0.006). Transplant-related mortality (TRM) and relapse incidence at 3 years were 4.3 and 30.4%, respectively. Patients receiving repeated infusions of zoledronic acid had a lower TRM as compared to those receiving 1 or 2 administration of the drug (0 vs. 16.7%, p = 0.01). Five-year overall survival (OS) and disease-free survival (DFS) for the whole cohort were 67.2 and 65.2%, respectively, with a trend toward a better OS for patients receiving 3 or more infusions (73.1 vs. 50.0%, p = 0.05). The probability of GvHD/relapse-free survival was significantly worse in patients receiving 1–2 infusions of zoledonic acid than in those given ≥3 infusions (33.3 vs. 70.6%, respectively, p = 0.006). Multivariable analysis showed an independent positive effect on outcome given by repeated infusions of zoledronic acid (HR 0.27, p = 0.03). These data indicate that the use of zoledronic acid after TcRαβ/CD19-cell depleted haploHSCT is safe and may result in a lower incidence of acute GvHD, chronic GvHD, and TRM

Low Rates of Breakthrough COVID-19 Infection After SARS-CoV-2 Vaccination in Patients With Inflammatory Bowel Disease

We demonstrate low rates of breakthrough coronavirus disease 2019 (COVID-19) infection and mild course of illness following severe acute respiratory syndrome coronavirus 2 vaccination in a large cohort of inflammatory bowel disease patients. Residence in southern United States and lower median anti-receptor binding antibody level were associated with development of COVID-19

Impact of SARS-CoV-2 Vaccination on Inflammatory Bowel Disease Activity and Development of Vaccine-Related Adverse Events: Results From PREVENT-COVID

Severe acute respiratory syndrome coronavirus 2 vaccination is recommended for all individuals with inflammatory bowel disease (IBD), including those on immunosuppressive therapies; however, little is known about vaccine safety and efficacy in these patients or the impact of vaccination on IBD disease course.We evaluated coronavirus disease 2019 (COVID-19) vaccine–related adverse events (AEs) and the effect of vaccination on IBD disease course among participants in the PREVENT-COVID (Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID) study, a prospective, observational cohort study. Localized and systemic reactions were assessed via questionnaire. Disease flare was defined by worsening IBD symptoms and change in IBD medications. Outcomes were stratified by vaccine type and IBD medication classes.A total of 3316 individuals with IBD received at least 1 COVID-19 vaccine. Injection site tenderness (68%) and fatigue (46% dose 1, 68% dose 2) were the most commonly reported localized and systemic AEs after vaccination. Severe localized and systemic vaccine-related AEs were rare. The mRNA-1273 vaccine was associated with significantly greater severe AEs at dose 2 (localized 4% vs 2%, systemic 15% vs 10%; P < .001 for both). Prior COVID-19 infection, female sex, and vaccine type were associated with severe systemic reactions to dose 1, while age <50 years, female sex, vaccine type, and antitumor necrosis factor and vedolizumab use were associated with severe systemic reactions to dose 2. Overall rates (2%) of IBD flare were low following vaccination.Our findings provide reassurance that the severe acute respiratory syndrome coronavirus 2 vaccine is safe and well tolerated among individuals with IBD, which may help to combat vaccine hesitancy and increase vaccine confidence.The severe acute respiratory syndrome coronavirus 2 vaccine is safe and well tolerated among individuals with inflammatory bowel disease (IBD). Severe localized and systemic vaccine-related adverse events were rare, and rates of IBD flare were low (2%) following severe acute respiratory syndrome coronavirus 2 vaccination in a cohort of 3316 participants with IBD

Lateral osteotomy plus hump resection vs hump re-modeling without lateral osteotomy: impact on frontal nasal view

This article reviews the personal experience and evolution of osteotomy approach in the last years of practice to obtain a natural appearance of the nasal pyramid in the frontal view. The aim is to analyse the long-term results after rhinoplasty on nasal width in two different cohorts of patients subjected to lateral osteotomy plus hump resection vs. hump re-modeling without lateral osteotomy considering the impact on frontal nasal view and how this relates to changes observed over time in the nasal width and contour. The study was carried out between January 2010 and December 2013, considering 42 patients undergoing primary rhinoplasty. Comparisons were made between the change in the dorsal width of the nasal pyramid at the level of the medial canthi, at the level of the inferior margin of the orbital rim, of ventral width of the nasal pyramid at the level of the medial canthi and at the level of the inferior margin of the orbital rim. In the first group, we found significant postoperative mean widening of the intercanthal dorsal width and narrowing of the ventral, while in the second group there was significant postoperative mean narrowing of the dorsal width both at level of the medial canthi and the anterior junction of the nasal bones. Our analysis seems to point out that dorsal grafting is useful for re-shaping the nasal profile with a persistent and harmonious correction of the dorsal frontal dimension of the nose. Simple hump removal/repositioning may be considered in selected instances to avoid lateral osteotomies. It also seems of paramount importance to tailor osteotomies according to nasal bone anatomy: large, strong and curved bones deserve aggressive narrowing by lateral and medial continuous osteotomies without periosteal elevation, although this approach may be insufficient to narrow the upper dorsal aspect of the nose

Effetti e meccanismi molecolari della Curcumina nelle leucemie linfoblasti che acute dell’età pediatrica.

La curcumina, componente della curcuma presente nei rizomi della Curcuma Longa, sembra avere effetti antineoplastici per cui è stata studiata quale potenziale agente per la prevenzione e il trattamento di varie neoplasie in quanto bloccherebbe la trasformazione cellulare, proliferazione delle cellule neoplastiche inducendo apoptosi. Ci proponiamo di studiare l’effetto della curcumina su cellule leucemiche della linea B e T, in singolo e combinato con farmaci convenzionali utilizzati nei protocolli delle leucemie e con DZnep inibitore indiretto del regolatore epigenetico EZH2. .METODI: Sono state utilizzate, come modelli in vitro, due linee cellulari (SuP B-15 e Jurkat) per verificare gli effetti della curcumina a concentrazioni scalari e in combinazione con diversi agenti chemioterapici (Daunoblastina, L-asparaginasi, metotrexate) e con l’ inibitore di EZH2 (DZnep). Abbiamo studiato l’apoptosi, il ciclo cellulare, la produzione cellulare di ROS prima e dopo trattamento e effettuato l’analisi al microscopio confocale. RISuLTATI: I risultati preliminari mostrano che la curcumina inibisce in maniera dose-dipendente la proliferazione delle cellule di entrambe le linee cellulari dopo 24 ore di trattamento (p <0.05). La colorazione con Annessina V mostra un significativo incremento dell’apoptosi precoce (86% in Jurkat e 82% in SuP p<0.05) particolarmente con curcumina in singolo e in combinato con Daunoblastina e DZnep . Abbiamo ulteriormente dimostrato con il microscopio confocale, a sostegno dei risultati ottenuti, che la curcumina, internalizzata nelle cellule, determina la frammentazione citoplasmatica e in parte quella nucleare. Questi primi dati indicano che la curcumina potrebbe migliorare l’efficacia degli agenti chemioterapici attraverso la regolazione dei loro meccanismi molecolari

Use of ruxolitinib to control graft-versus-host–like disease in Omenn syndrome and successfully bridging to HSCT

NO ABSTRAC

Immune Modulation Properties of Zoledronic Acid on TcRγδ T-Lymphocytes After TcRαβ/CD19-Depleted Haploidentical Stem Cell Transplantation: An analysis on 46 Pediatric Patients Affected by Acute Leukemia

TcRαβ/CD19-cell depleted HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) represents a promising new platform for children affected by acute leukemia in need of an allograft and lacking a matched donor, disease recurrence being the main cause of treatment failure. The use of zoledronic acid to enhance TcRγδ+ lymphocyte function after TcRαβ/CD19-cell depleted haplo-HSCT was tested in an open-label, feasibility, proof-of-principle study. Forty-six children affected by high-risk acute leukemia underwent haplo-HSCT after removal of TcRαβ+ and CD19+ B lymphocytes. No post-transplant pharmacological graft-versus-host disease (GvHD) prophylaxis was given. Zoledronic acid was administered monthly at a dose of 0.05 mg/kg/dose (maximum dose 4 mg), starting from day +20 after transplantation. A total of 139 infusions were administered, with a mean of 3 infusions per patient. No severe adverse event was observed. Common side effects were represented by asymptomatic hypocalcemia and acute phase reactions (including fever, chills, malaise, and/or arthralgia) within 24–48 h from zoledronic acid infusion. The cumulative incidence of acute and chronic GvHD was 17.3% (all grade I-II) and 4.8% (all limited), respectively. Patients given 3 or more infusions of zoledronic acid had a lower incidence of both acute GvHD (8.8 vs. 41.6%, p = 0.015) and chronic GvHD (0 vs. 22.2%, p = 0.006). Transplant-related mortality (TRM) and relapse incidence at 3 years were 4.3 and 30.4%, respectively. Patients receiving repeated infusions of zoledronic acid had a lower TRM as compared to those receiving 1 or 2 administration of the drug (0 vs. 16.7%, p = 0.01). Five-year overall survival (OS) and disease-free survival (DFS) for the whole cohort were 67.2 and 65.2%, respectively, with a trend toward a better OS for patients receiving 3 or more infusions (73.1 vs. 50.0%, p = 0.05). The probability of GvHD/relapse-free survival was significantly worse in patients receiving 1–2 infusions of zoledonic acid than in those given ≥3 infusions (33.3 vs. 70.6%, respectively, p = 0.006). Multivariable analysis showed an independent positive effect on outcome given by repeated infusions of zoledronic acid (HR 0.27, p = 0.03). These data indicate that the use of zoledronic acid after TcRαβ/CD19-cell depleted haploHSCT is safe and may result in a lower incidence of acute GvHD, chronic GvHD, and TRM