Search

The use of anti-thymocyte globulin (ATG) as part of conditioning to prevent graft-versus-host disease (GVHD) may severely impair immune reconstitution (IR). We analyzed relationships between ATG exposure, the recipient lymphocyte count, IR, and transplant outcome. We retrospectively reviewed patients aged ≤ 18 years who underwent allogeneic HSCT between April 2005 and April 2020. The outcomes of interest included the incidence of GVHD, overall survival (OS), and IR. IR was analyzed through thymic magnetic resonance imaging (MRI) and by quantifying T CD4+ and recent thymic emigrants (RTEs). The ATG-exposed group was split into a low ATG/lymphocyte ratio subgroup (ratio < 0.01) and a high ATG/lymphocyte ratio subgroup (ratio > 0.01). The low ratio subgroup had a higher incidence of GVHD (29 [59%] vs. 7 [16.6%]) but a better IR in both laboratory and MRI imaging assessments (p < 0.0001). The median thymic volume in the low ratio subgroup was significantly higher (14.7 cm3 vs. 4.5 cm3, p < 0.001). This was associated with a better OS and lower transplant-related mortality (TRM) (80.4% vs. 58.0%, p = 0.031) and (13.1% vs. 33.0%, p = 0.035). An individualized approach to ATG dosing allows for the obtainment of rapid thymic reconstitution and the best transplant-related outcomes. [ABSTRACT FROM AUTHOR]

Janus kinases (JAK) are a family of tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) that transduce cytokine-mediated signals through the JAK–STAT metabolic pathway. These kinases act by regulating the transcription of specific genes capable of inducing biological responses in several immune cell subsets. Inhibition of Janus kinases interferes with the JAK–STAT signaling pathway. Besides being used in the treatment of cancer and inflammatory diseases, in recent years, they have also been used to treat inflammatory conditions, such as graft-versus-host disease (GVHD) and cytokine release syndrome as complications of allogeneic hematopoietic stem cell transplantation and cell therapy. Recently, the FDA approved the use of ruxolitinib, a JAK1/2 inhibitor, in the treatment of acute steroid-refractory GVHD (SR-aGVHD), highlighting the role of JAK inhibition in this immune deregulation. Ruxolitinib was initially used to treat myelofibrosis and true polycythemia in a high-dose treatment and caused hematological toxicity. Since a lower dosage often could not be effective, the use of ruxolitinib was suspended. Subsequently, ruxolitinib was evaluated in adult patients with SR-aGVHD and was found to achieve a rapid and effective response. In addition, its early low-dose use in pediatric patients affected by GVHD has proved effective, safe, and reasonably preventive. The review aims to describe the potential properties of ruxolitinib to identify new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Plexiform neurofibromas (PN) are congenital tumors that affect up to 50% of individuals with neurofibromatosis type 1. Despite their benign nature, they can grow rapidly and cause severe morbidities. Selumetinib, an inhibitor of mitogen-activated protein kinase (MEK) 1 and 2, was reported to induce a clinical response in pediatric subjects with inoperable PN. Objective: The aim of this paper is to describe a prospective case series of patients treated with selumetinib with emphasis on drug adverse events. Patients and methods: All the subjects who received selumetinib at the Pediatric Department of Scientific Research Institute and Hospital "Burlo Garofolo", from November 2017 to January 2020, were progressively included. We monitored the patients with a follow-up visit every 3 months. MRI or CT scans to monitor the growth of the tumor were performed after 3 months of treatment, and then every 6–9 months. Results: Selumetinib was prescribed to nine children, with a total of 17 inoperable PN. The mean follow-up period was 12 months. During the follow-up, one patient experienced an ischemic stroke, unrelated to the treatment. Only minor adverse events were observed: six individuals developed gastrointestinal side effects, seven patients presented a mild form of acne, six had paronychia, four developed irritability, and two showed a mild increase in creatine kinase. None of the patients stopped the treatment. Tumor reduction > 20% was recorded in 16 out of 17 PN (94%). One PN remained stable. No tumor growth was recorded during the treatment. Conclusions: In this case series, selumetinib appears to be effective and safe for the pediatric population. [ABSTRACT FROM AUTHOR]

Background: Total body irradiation (TBI) is a mandatory step for patients with acute lymphoblastic leukemia (ALL), undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In the past, amylases have been reported to be a possible sign of TBI toxicity. We investigated the relationship between total amylases (TA) and transplant-related outcomes in pediatric recipients. Methods: We retrospectively analyzed the medical records of all the patients who underwent allogeneic HSCT between January 2000 and November 2019. The inclusion criteria were the following: recipient's age between 2 and 18, diagnosis of ALL, no previous transplantation, and use of TBI-based conditioning. The serum total amylase and pancreatic amylase were evaluated before, during, and after transplantation. Cytokines and chemokines assays were retrospectively performed. Results: 78 patients fulfilled the inclusion criteria. Fifty-seven patients were treated with fractionated TBI, and 21 with a single-dose regimen. The overall survival (OS) was 62.8%. Elevated values of TA were detected in 71 patients (91%). The TA were excellent in predicting the OS (AUC = 0.773; 95% CI = 0.66–0.86; p < 0.001). TA values below 374 U/L were correlated with a higher OS. The highest mean TA values (673 U/L) were associated with a high disease-progression mortality rate. The TA showed a high predictive performance for disease progression-related death (AUC = 0.865; 95% CI = 0.77–0.93; p < 0.0001). Elevated TA values were also connected with significantly higher levels of proinflammatory cytokines, such as TNF-α, IL-6, and RANTES (p < 0.001). Conclusions: this study shows that TA is a valuable predictor of post-transplant OS and increased risk of leukemia relapse. [ABSTRACT FROM AUTHOR]