Haploidentical IL-15/41BBL activated and expanded natural killer cell infusion therapy after salvage chemotherapy in children with relapsed and refractory leukemia

Cancer Letters
M VelaAntonio Pérez-Martínez

Abstract

Primary refractory or relapsed pediatric leukemia yield significant morbidity and mortality, with long-term survival rates <40%. Here we present a post-hoc analysis assessing safety and efficacy of infusing activated and expanded Natural Killer cells (NKAE) from haploidentical donors in patients from 2 clinical trials. In total, 18 children, adolescents and young adults with relapse or refractory acute leukemia were treated with two cycles of rescue chemotherapy followed by fresh NKAE cells infusions and low doses of IL-2. The overall response rate, complete remission achievement at the end of the study, was 72% (13 of 18). We infused 52 NKAE cell products containing a median of 6.76 × 106 NK cells/kg (0.7-34.16) and 0.49 × 106 T cells/kg (0-11). All infusions were well tolerated with no graft versus host disease nor other serious adverse events. Among the 14 patients who completed treatment, 4 of them are alive and leukemia-free more than 750 days post-transplant. We conclude that infusion of fresh NKAE cell therapy is feasible and safe in heavily pretreated pediatric population, and should be further investigated in advanced-phase clinical trials as well as a consolidation therapy to decrease relapse in patients with high-ris...Continue Reading

Citations

May 18, 2020·Stem Cells Translational Medicine·May Sabry, Mark W Lowdell
Aug 21, 2019·Frontiers in Immunology·Maria VelaAntonio Pérez-Martínez
Jun 26, 2020·Frontiers in Cell and Developmental Biology·Daria S ChulpanovaValeriya V Solovyeva
Dec 9, 2020·Journal of Hematology & Oncology·Jing Xu, Ting Niu
Jan 13, 2021·Cytotherapy·Soumyadipta KunduMichael O'Dwyer
Jan 1, 2021·International Immunopharmacology·Shuling ZhangFengping Shan
Feb 6, 2021·Cancers·Adrián FernándezAntonio Pérez-Martínez
Dec 12, 2020·Frontiers in Immunology·Helmi AlfarraTony Reiman
Mar 21, 2021·Scientific Reports·Iñigo TerrénFrancisco Borrego
Dec 23, 2021·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Lanlan GaoChangxin Huang

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