Haploidentical Stem Cell Transplantation in Children With Hematological Malignancies Using αβ+ T-Cell Receptor and CD19+ Cell Depleted Grafts: High CD56dim/CD56bright NK Cell Ratio Early Following Transplantation Is Associated With Lower Relapse Incidence and Better Outcome

Abstract

We prospectively analyzed outcomes of haploidentical hematopoietic stem cell transplantation using αβ⁺ T-cell receptor/CD19⁺ depleted grafts. Sixty-three transplantations were performed in 60 patients. Twenty-eight patients were diagnosed with acute lymphoblastic leukemia (ALL), 27 patients were diagnosed with acute myelogenous leukemia, and in eight other hematological malignancies were diagnosed. Twenty-three were in first complete remission (CR), 20 in second CR, 20 beyond second CR. Four patients developed graft failure. Median time to neutrophil and platelet recovery was 14 (range 9-25) and 10 days (range 7-30), respectively. The probability of non-relapse mortality (NRM) by day +100 after transplantation was 10 ± 4%. With a median follow-up of 28 months, the probability of relapse was 32 ± 6% and disease-free survival was 52 ± 6%. Immune reconstitution was leaded by NK cells. As such, a high CD56^dim/CD56^bright NK cell ratio early after transplantation was associated with better disease-free survival (DFS) (≥3.5; 77 ± 8% vs. <3.5; 28 ± 5%; p = 0.001) due to lower relapse incidence (≥3.5; 15 ± 7% vs. <3.5; 37 ± 9%; p = 0.04). T-cell reconstitution was delayed and associated with severe infections after transplant. Viral reactivation/disease and presence of venooclusive disease of liver in the non-caucasian population had a significant impact on NRM. αβ⁺ T-cell receptor/CD19⁺ cell-depleted haploidentical transplant is associated with good outcomes especially in patients in early phase of disease. A rapid expansion of "mature" natural killer cells early after transplantation resulted on lower probability of relapse, suggesting a graft vs. leukemia effect independent from graft-vs.-host reactions.

Keywords: NK cells; T-cell depletion; acute leukemia; children; haploidentical transplantation; immune reconstitution.