A phase II clinical trial of infusing haploidentical K562-mb-IL15-41BBL
activated and expanded Natural Killer cells as consolidation therapy for
pediatric acute myeloblastic leukemia
Abstract
Background. Acute myeloid leukemia (AML) accounts for approximately 25%
of pediatric leukemia. The long term overall survival rate now
approaches 70%, but up 30% relapse. The anti-leukemia properties of
Natural Killer (NK) cells and its safety profile has been reported
previously at different phases of AML treatment. We proposed a phase II
open, a prospective multicenter, non-randomized clinical trial for
adoptive infusion of haploidentical K562-mb15-41BBL activated and
expanded Natural Killer (NKAE) cells as a consolidation strategy in
children with favorable and intermediate-risk AML who were in first
complete remission after chemotherapy (NCT02763475). Previous to NKAE
cell infusion, patients received a lymphodepleting regimen. After NKAE
cell infusion, patients received low doses (1×106/IU/m2) of IL-2
subcutaneously every 48 hours for 2 weeks. Procedure. Seven patients,
median age 7.4 years (range, 0.78–15.98), received 13 infusions of NKAE
cells, with a median of 36.44×106 NKAE cells/kg (range, 6.92–193.2×106
cells/kg). Results. Three pair donor-recipient were KIR–HLA-mismatched.
Donor KIR haplotype score was better in two cases, and neutral in the
rest of the cases. Chimerism was observed in 4 patients median chimerism
0.065%, (range 0.05-0.27%). With a median of follow up of 33 moths, 6
(85.7%) patients remain alive and in complete remission. The 3-year
overall survival was 83.3% (95% confidence interval 68.1-98.5), and
the 3-year relapse cumulative incidence was 28.6% (95% confidence
interval 11.5-45.7). Conclusions. This study shows that NKAE cell
infusion as a consolidation strategy was feasible and safe but could not
improve the pediatric AML relapse rate in this small cohort.