Planning GvHD preemptive therapy: risk factors, biomarkers, and prognostic scores
Jacob Rozmus1, John E Levine2, Kirk R Schultz2
1Pediatric Hematology Oncology and BMT, BC Children's Hospital Research Institute and University of British Columbia, Vancouver, BC, Canada.
Insights
Preventing graft-versus-host disease (GvHD) after transplantation remains challenging. New risk algorithms using biomarkers show promise for preemptive interventions against acute GvHD (aGvHD) and chronic GvHD (cGvHD).
Area of Science:
- Hematopoietic Cell Transplantation (HCT)
- Immunology
- Transplantation Medicine
Background:
- Preventing acute and chronic graft-versus-host disease (aGvHD and cGvHD) is critical in allogeneic HCT.
- Current preventative strategies do not completely eliminate GvHD development.
- GvHD remains a significant complication following HCT.
Purpose of the Study:
- To review the current state of preemptive algorithms for aGvHD and cGvHD.
- To discuss therapeutic interventions based on these algorithms.
- To identify future directions for validated preemptive approaches in HCT.
Main Methods:
- Utilizing posttransplant immune biomarker profiling early after HCT.
- Development and validation of risk assignment algorithms for aGvHD.
- Development of risk assignment algorithms for cGvHD based on day 100 measurements.
Main Results:
- A validated risk assignment algorithm for aGvHD has been developed.
- Preemptive approaches based on this algorithm can decrease aGvHD and mortality in high-risk patients.
- Risk assignment algorithms for cGvHD are available for future intervention trials.
Conclusions:
- Immune biomarker profiling enables validated risk assignment for aGvHD.
- Preemptive strategies show potential for reducing aGvHD and mortality.
- Further development is needed to validate cGvHD algorithms and interventions.
Abstract:
Prevention of acute and chronic graft-versus-host disease (aGvHD and cGvHD) is an important objective of allogeneic hematopoietic cell transplantation (HCT). While there is has been significant progress in preventative approaches in the peritransplant period to minimize development of GvHD, no preventative approach has completely eliminated development of either aGvHD or cGvHD. Recently, posttransplant immune biomarker profiling early post-HCT by the Mount Sinai Acute GvHD International Consortium group has resulted in a validated risk assignment algorithm and development of preemptive approaches to decrease aGvHD and mortality in high-risk patients. cGvHD risk assignment algorithms have been developed based on measurements at day 100 and may be used for future preemptive intervention trials to minimize cGvHD. This article discusses the current state of the art in aGvHD and cGvHD preemptive algorithms and therapeutic interventions and what is needed to move these into validated approaches.
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