Adoptive Cellular Therapies in Pediatric Leukemia Patients After Allogeneic-Hematopoietic Stem Cell Transplants
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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides a curative potential for high-risk patients with leukemia following first-line therapies, driven by potent immune cell-dependent anti-tumour activities. Although deep remission can be achieved, many patients relapse after allo-HSCT, and further treatment options are scarce. Given the potent immune cell-mediated anti-leukemic effects of allo-HSCT, adoptive cellular therapies (ACTs) have been explored as an adjunctive therapy to enhance the efficacy of allo-HSCT or to treat patients who relapse after allo-HSCT. Interestingly, evidence suggests a stratified therapeutic approach is warranted between pediatric and adult leukemic cases, due to differences in genetic mutations and treatment tolerability. However, pediatric-specific investigations are limited, especially in the cellular therapeutic landscape to treat relapse after allo-HSCT. Known severe toxicities attributed to ACTs need to be addressed for this younger population to ensure prolonged quality of life. This review summarizes the current landscape of ACTs, including donor lymphocyte infusion, chimeric Ag receptor-T cell, NK cell, and double-negative T cell therapies, for treating pediatric leukemia post allo-HSCT, highlighting efficacy, safety, and gaps in pediatric-specific data to guide future research.
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides a curative potential for high-risk patients with leukemia following first-line therapies, driven by potent immune cell-dependent anti-tumour activities. Although deep remission can be achieved, many patients relapse after allo-HSCT, and further treatment options are scarce. Given the potent immune cell-mediated anti-leukemic effects of allo-HSCT, adoptive cellular therapies (ACTs) have been explored as an adjunctive therapy to enhance the efficacy of allo-HSCT or to treat patients who relapse after allo-HSCT. Interestingly, evidence suggests a stratified therapeutic approach is warranted between pediatric and adult leukemic cases, due to differences in genetic mutations and treatment tolerability. However, pediatric-specific investigations are limited, especially in the cellular therapeutic landscape to treat relapse after allo-HSCT. Known severe toxicities attributed to ACTs need to be addressed for this younger population to ensure prolonged quality of life. This review summarizes the current landscape of ACTs, including donor lymphocyte infusion, chimeric Ag receptor-T cell, NK cell, and double-negative T cell therapies, for treating pediatric leukemia post allo-HSCT, highlighting efficacy, safety, and gaps in pediatric-specific data to guide future research.