Advances in cellular therapies for pediatric patients have created many opportunities for improved survival with reduced morbidity. This article reviews current cellular therapies in pediatric hematological malignancy, including the most updated practices in hematopoietic stem cell transplant and the use of chimeric antigen receptor (CAR) therapy in T cells. Hematopoietic stem cell transplant has evolved with improvements in chemotherapy regimens, immunosuppression, and donor-matching options. Novel therapies in development which will likely further improve the options for patients are reviewed including Natural Killer, Regulatory T-cells and αβ depletion.
Hematopoietic stem cell (HPSC) transplant is the most common and standardized cellular therapy. Advances such as using haploidentical matches have improved the available donor pool, and product manipulations such as αβ T-cell depletion show an improved safety profile and reduced risk of complications such as graft-versus-host disease and infection caused by delayed engraftment.
Chimeric antigen receptor therapies have provided an essential bridge to HPSC transplant for patients with relapsed/refractory leukemia and may prove to be an effective stand-alone therapy.
Regulatory T cells show promise as an alternative to common medications with a high side effect profile, such as glucocorticoids.
Natural killer cells are a focus of current studies, both for enhancement within HPSC grafts and for stand-alone therapy. Their unique profile as a part of the innate immune system makes them an ideal target for future treatments.
The Foundation for the Accreditation of Cellular Therapies in collaboration with the international Joint Accreditation Committee provides guidance on maintaining the safety, purity, and potency of cellular therapies.
Cellular therapy for pediatric hematologic malignancies has made significant advances in recent years. New technologies for hematopoietic stem cell transplant allow broadened opportunities for finding a suitable donor (eg, haploidentical), as well as manipulations such as αß T-cell depletions and umbilical cord blood expansion. The development of Chimeric antigen receptor (CAR) T-cell therapy has resulted in a significant improvement in mortality for relapsed/refractory leukemia. CAR technology shows promise as other cell lines are developed into adoptive therapies, including natural killer cells and regulatory T cells (Tregs). Regulatory requirements must keep up with these advances, which sometimes causes confusion. These topics are highlighted and addressed in this article.