In November 2022, professor Erlie Jiang and his team from Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science published a crucial study in the American Journal of Hematology, focusing on the impact of the Composite Immune Risk Score on survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Analyzing 1838 cases, the study highlighted the score’s potential to predict overall survival, offering a new tool for personalized post-transplant care. This research marks a significant advancement in understanding and managing hematological malignancies, promising to improve patient outcomes.
Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for patients with malignant and non-malignant hematological disorders. Despite advancements in transplantation techniques and post-transplant care, infection-related mortality remains a significant challenge. This study aimed to address this challenge by quantitatively assessing immune reconstitution after HSCT. The goal was to develop a Composite Immune Risk Score that simplifies the assessment of a patient’s immune system recovery into a formula. This score would help in identifying patients at high risk after allogeneic HSCT, enabling clinicians to target efforts towards the prevention and control of infection, ultimately improving patient outcomes.
The immune system’s reconstitution after HSCT is critical for patient survival. A delayed or inadequate immune recovery can lead to increased susceptibility to infections, which are major causes of morbidity and mortality in the post-transplant period. Previous studies have highlighted the importance of various immune cells, such as neutrophils, lymphocytes, natural killer cells, T cells, and B cells, in the recovery process. However, a comprehensive and quantitative analysis that integrates the role of these cells into a single predictive model has been lacking.
This study performed a retrospective analysis of 11,150 post-transplant immune profiles from 1945 patients who underwent HSCT between 2012 and 2020. The patients’ immune cell counts were collected during days 91-180 after allogeneic HSCT, a critical period for immune system reconstitution. Using a subset of patients (n=729) as a training set, the study identified a composite immune signature. This signature integrated counts of neutrophils, total lymphocytes, natural killer cells, total T cells, CD4+ T cells, and B cells from peripheral blood samples. A statistical model was then developed to compute the Composite Immune Risk Score based on these immune parameters.
The validation (n=284) and test (n=391) sets of patients were used to assess the predictive value of the Composite Immune Risk Score. The score was strongly associated with early mortality, with hazard ratios of 3.64 (95% Confidence Interval [C.I.] 1.55 – 8.51; p = .0014) and 2.44 (95% C.I., 1.22 – 4.87; p = .0087), respectively. In a multivariate analysis, accounting for other potential risk factors, a high Composite Immune Risk Score during days 91-180 post-transplant was confirmed as an independent risk factor for early mortality (Hazard Ratio, 1.80; 95% C.I., 1.28 – 2.55; p = .00085).
The study explored the evolution of immune reconstitution post-allogeneic hematopoietic stem cell transplantation using a comprehensive dataset, identifying critical periods where immune cell counts predict mortality. By applying a ten-fold cross-validation method, it found that immune signatures during days 91-180 and 271-360 after transplantation significantly predicted mortality, with the former also being significant in validation sets. This period’s immune profile was distilled into a Composite Immune Risk Score using logistic regression, incorporating white blood cell, neutrophil, lymphocyte counts, and percentages, alongside NK and T cell percentages, to quantify mortality risk.
This figure illustrates the discovery and validation of a Composite Immune Risk Score during days 91-180 post-transplant for predicting early mortality. This score, based on immune cell percentages, notably distinguished high-risk from low-risk patients in terms of early mortality across training, validation, and test sets. High-risk patients, defined by a score greater than 2.50, showed significantly higher early mortality rates. This scoring system was effectively validated in a separate test set, confirming its predictive value for early mortality across different patient cohorts. The composite score’s validation underscores its potential as a critical tool for post-transplant patient management and risk stratification.
The development of the Composite Immune Risk Score represents a significant advancement in the management of HSCT patients. By quantitatively assessing the immune reconstitution and identifying high-risk individuals, clinicians can tailor their approach to each patient’s needs. This could include more aggressive monitoring, prophylactic measures to prevent infection, or therapeutic interventions to enhance immune recovery. Furthermore, the Composite Immune Risk Score could be used as a tool in clinical trials to stratify patients based on their risk of early mortality, allowing for more targeted research into improving HSCT outcomes.
The Composite Immune Risk Score is a novel, easy-to-compute tool that has the potential to significantly impact the field of HSCT. By identifying patients at high risk of early mortality due to inadequate immune reconstitution, this score can guide targeted efforts for infection prevention and control. Ultimately, the application of this score in clinical practice could lead to improved survival rates and quality of life for patients undergoing allogeneic HSCT.
Future studies should focus on validating the Composite Immune Risk Score in larger, diverse patient populations and exploring its utility in guiding clinical decision-making. Additionally, research into interventions that can modulate the immune system based on the risk score could provide new strategies for reducing post-transplant mortality.
