Natural killer cell infusion after stem cell transplantation for leukemia

Children with leukemia are treated with standardized chemotherapy and in most cases this treatment is curative. However, and in accordance with international guidelines, patients are eligible for allogeneic hematopoietic stem cell transplantation (HSCT) in case of leukemia characterized by well defined high-risk parameters and in case of relapsed disease following initial successful remission induction therapy. Historically, HLA-matched sibling donors were the first donors to be used, but due to ongoing improvements in HLA typing technology, graft manipulation and supportive care, a matched unrelated (MUD) or mismatched family donor (MMFD) is nowadays a feasible and widely accepted alternative. However, leukemia relapse after HSCT remains the main reason for treatment failure. Following HSCT with MUD and MMFD, T cell reconstitution is delayed up to 6-12 months post transplant, and thus a potential T cell mediated graft versus leukemia (GvL) effect may be impaired. In contrast, there is rapid recovery of natural killer (NK) cells, which have been reported to exert an anti-leukemic effect. Still, the functional capacity of the early regenerating NK cells seems limited. In vitro, the functional and cytolytic properties of NK cells can be augmented by stimulation with cytokines, e.g. interleukin 15 (IL-15). We aim to exploit this NK-cell mediated potential by adoptive transfer of ex vivo IL15-activated donor NK cells with the final aim to enhance immune reconstitution and reduce residual tumor burden in the early post transplant setting when tumor levels are low.

Adoptive transfer of ex vivo IL15-activated donor NK cells enhance immune reconstitution and reduce residual tumor burden in the early post transplant setting.

During the first year after transplantation and NK cell infusion, patients will be monitord frequently, according to our current standards for follow-up of pediatric HSCT recipients, to address primary and secondary objectives. Timepoints are pre-SCT, weekly after SCT in the first 10 weeks, 12, 16, 20, 24, and 52 weeks post-SCT. Thereafter, patients will be followed until adulthood and subsequently transferred to the late feects clinic according to our standard procedures for allogeneic stem cell tranplantation recipients.

Patients will receive one infusion of 5-10x10e6 ex vivo IL-15-activated donor NK cells per kg body weight (maximum dose: 200x10e6) at 4-12 weeks after transplantation.