Research Topic

Novel Immunological Biomarkers for Allogeneic HSCT Outcome

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Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option for many malignant and non-malignant hematological disorders. Recent improvements in transplantation procedures, such as (i) reduced-toxicity conditioning regimens; (ii) improved patient selection; and (iii) better ...

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option for many malignant and non-malignant hematological disorders. Recent improvements in transplantation procedures, such as (i) reduced-toxicity conditioning regimens; (ii) improved patient selection; and (iii) better supportive care, including infection prophylaxis, have enabled us to extend the application of this intensive treatment to more patients, including older patients and those with severe co-morbidities. Overall, improved supportive care of patients undergoing transplantation, together with advances in the prevention and treatment of HSCT-related complications, have led to a decrease in transplant-related morbidity and mortality in the past decade.

Nonetheless, HSCT is still burdened with remarkable toxicities, which have a major impact on transplant outcome, in both the long-term and the short-term. Leading causes of transplant-related morbidity and mortality include infection, and acute (aGvHD) and chronic graft-versus-host disease (cGvHD). Moreover, the recent introduction of novel medications for disease control has further increased the occurrence of less frequent complications such as Transplant-Associated Microangiopathy (TAM) and Veno-Occlusive Disease (VOD). Unfortunately, clinically-based risk scores, such as the standard HSCT co-morbidity- index, often fail to identify patients who will develop the most severe complications during and post-HSCT. Therefore, developing more effective strategies for the prediction and prevention of transplant complications remains an important unmet medical need.

In this setting, the use of immunological biomarkers holds great promise since these non-invasive and reliable laboratory tests will potentially present several advantages including: (i) the prediction of transplant complications prior to the appearance of related clinical symptoms; (ii) the prediction of peak severity before clinical progression, and (iii) the identification of patients who will not respond to treatment, and who are at particularly high risk for subsequent morbidity and mortality. Timely recognition of high-risk patients will then provide a window for implementing additional prophylactic or preemptive strategies, potentially improving the final outcome of allogeneic HSCT. Recently, several potential immunological biomarkers have been identified for use in allogeneic HSCT, ranging from serum proteins to immune cell subsets. These include serum biomarkers such as cytokines, elafin, ST2, REG3α, TNFR1 and IL2Rα. They also include cellular biomarkers such as T cell receptor excision circles (TRECs), regulatory T cells and stem memory T cells (TSCM). Moreover, recent studies indicate that the intestinal microbiota may be an important factor in determining the outcome of allogeneic HSCT. The potential use of these biomarkers in clinical practice would allow for the early identification of patients at risk for major HSCT complications, offering a new tool for individualized prophylaxis or preemptive treatments, leading to reduced transplant-related mortality. Nevertheless, no single biomarker or panel of biomarkers has been yet validated for clinical use via large multi-center trials.

In this Research Topic, we aim to gather Original Research and Review articles, as well as Clinical Trials and Case Reports, on studies focused on novel immunological biomarkers that can be applied to predict comprehensive allogeneic HSCT outcomes such as overall survival; transplant-related mortality; and the incidence of short-term and long-term HSCT related complications.


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