Neuroblastoma (NBL) is the most common extracranial solid tumor in childhood. Despite intense treatment, children with this high-risk disease have a poor prognosis. Immunotherapy showed a significant improvement in event-free survival in high-risk NBL patients receiving chimeric anti-GD2 in combination with cytokines and isotretinoin after myeloablative consolidation therapy. However, response to immunotherapy varies widely, and often therapy is stopped due to severe toxicities. Objective markers that help to predict which patients will respond or develop toxicity to a certain treatment are lacking. Immunotherapy guided via immune monitoring protocols will help to identify responders as early as possible, to decipher the immune response at play, and to adjust or develop new treatment strategies. In this review, we summarize recent studies investigating frequency and phenotype of immune cells in NBL patients prior and during current treatment protocols and highlight how these findings are related to clinical outcome. In addition, we discuss potential targets to improve immunogenicity and strategies that may help to improve therapy efficacy. We conclude that immune monitoring during therapy of NBL patients is essential to identify predictive biomarkers to guide patients towards effective treatment, with limited toxicities and optimal quality of life.
Acute Graft-versus-Host-Disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). We previously showed that early CD4+ T-cell reconstitution (CD4+IR) predicts survival after HCT. Here, we studied the relation between CD4+ IR and survival in patients who developed aGvHD. Pediatric patients receiving their first allogeneic HCT at the UMC Utrecht / Princess Máxima Center (UMC/PMC) or Memorial Sloan Kettering Cancer Center (MSK), were included. Primary outcomes were non-relapse mortality (NRM) and overall survival (OS), stratified for aGvHD and CD4+IR; defined as ³50 CD4+ T-cells/uL within 100 days after HCT, or prior to aGvHD onset. Multivariate and time-to-event Cox Proportional Hazard models were applied. 591 Patients (N= 276 UMC/PMC; N= 315 MSK) were included. NRM in patients with aGvHD grade III-IV with or without CD4+IR within 100 days after HCT was 30% vs 80% (p=0.02) at UMC/PMC and 5% vs 67% (p=0.02) at MSK. This associated with lower OS without CD4+IR; 61% vs. 20% (p=0.04) at UMC/PMC, and 75% vs. 33% (p=0.12) at MSK. Inadequate CD4+IR prior to aGvHD onset associates with significantly higher NRM; 74% vs 12% (p<0.001), and inferior OS; 24% vs 78% (p<0.001). In this retrospective analysis we demonstratethat early CD4+ IR, a simple and robust markerpredictive of outcomes after HCT,associates with survival after moderate to severe aGvHD.These associations need to be confirmed in a prospective manner but suggest that strategies to improve T-cell recovery after HCT may influence survival in patients developing aGvHD.
of autoimmune cytopenia (AIC) after allogeneic hematopoietic cell transplantation (HCT) is a serious complication requiring urgent intensification of immunosuppressive therapy. The pathophysiology and predictors of AIC are not completely understood. In this retrospective cohort analysis of 380 pediatric patients, we evaluated the incidence, outcomes, and related various variables, including immune reconstitution markers to AIC. Three hundred eighty patients (median age, 7.4 years; range, .1 to 22.7) were included, of which 30 patients (7.8%) developed AIC in 1 (n = 6), 2 (n = 6), or 3 (n = 16) cell lineages at a median of 133 days (range, 46 to 445) after HCT. Using multivariate analysis we found that chemo-naivety before HCT, acute graft-versus-host disease (aGVHD) grades II to IV, and serotherapy were associated with the development of AIC. Development of AIC was preceded by increased levels of IgM, IgA, and IgG. Immune profiles of total absolute lymphocytes were very similar between AIC patients and control subjects. However, CD3-CD16 + CD56 + natural killer cells, CD3 + T cells, CD3 + CD4 + T cell subset, and CD3 + CD8 + T cell subset were lower in AIC patients. Overall survival was good, at 83% (similar between AIC patients and control subjects). In conclusion, we identified chemo-naivety before HCT, preceding aGVHD grades II to IV, and serotherapy as predictors for development of AIC. Increasing levels of IgM, IgA, and IgG preceded AIC development. These data provide clues to further study the biology of AIC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.