Transplantation of T-Cell Depleted Peripheral Blood Haematopoietic Stem Cells from an HLA-Disparate Family Donor for Children with Hematological Malignancies.
Authors: Locatelli Franco , Pende Daniela , Comoli Patrizia , Zecca Marco , Giorgiani Giovanna , Perotti Cesare , Bernardo Maria Ester , Salvaneschi Laura , Maccario Rita , Moretta Alessandro , Moretta Lorenzo 
Published: October 2019

Transplantation of T-cell depleted peripheral blood hematopoietic stem cells (PBHSCT) from an HLA-disparate relative has been reported to cure a significant proportion of adults with hematological malignancies, especially if transplanted for myeloid leukemia from a natural killer (NK)-alloreactive donor. Information on effectiveness of this type of allograft for children is limited. We analysed 47 patients (26 M, 21 F; median age 8 years, range 2–21) given PBHSCT from an HLA-mismatched relative between January 1998 and April 2007 for acute lymphoblastic leukemia (ALL; N.23), acute myeloid leukemia (AML; N.17) and myelodysplastic syndrome (MDS; N.7). Only 4 out of 40 patients with acute leukemia were transplanted in 1st remission; in 14 cases the allograft was performed in presence of active disease. In 29 and 18 cases, the donor did or did not display NK-alloreactivity against the recipient, respectively. All patients were given T-cell depleted CD34+ cells, positively selected using the CliniMacs device (Miltenyi Biotech), after a myeloablative regimen. After January 2005, patients received T-cell lines or clones to accelerate immune recovery against the most frequent and life-threatening pathogens (EBV, CMV, Adenovirus, Aspergillus). No pharmacological immune suppression was given after PBHSCT. Primary and secondary graft failure occurred in 1 patient each at day +15 and +65, respectively. Both patients were successfully re-transplanted from the same donor. For engrafted patients, median time to neutrophil and platelet recovery was 12 (range, 9–16) and 13 days (range, 7–20), respectively. Incidence of grade III-IV acute and extensive chronic GVHD were 6% and 3%, respectively. Cumulative incidence of transplantation mortality of overall cohort was 25% (95%, CI 14–43); 10% (95%, CI 3–37) for patients who received the allograft after January 2005 and 35% (95%, CI 20–61) for those transplanted before (p<0.05). Ten out of the 47 patients experienced relapse at a median of 126 days after PBHSCT (range 55–220), the overall cumulative incidence of relapse being 25% (95% CI 15–45). With a median follow-up of 16 months (range 4–108), the 5-year estimate of disease-free survival (DFS) for the whole cohort was 50% (95%, CI 34–66); 70% (95%, CI 49–90), 20% (95%, CI 0–39) and 75% (95%, CI 33–100) in patients with ALL, AML and MDS, respectively (p<0.01). In children with acute leukaemia who did or did not receive the allograft from an NK-alloreactive donor, the cumulative incidence of relapse was 17% and 50%, respectively (p<0.05), while the DFS probability was 64% (95%, CI 46–83) and 17% (95%, CI 0–39), respectively (p<0.05). The DFS of the 18 patients with ALL transplanted from an NK-alloreactive donor was 81% (95%, CI 61–100). Donor-derived alloreactive NK cells emerged in the early phase after PBHSCT and persisted over time. T-cell depleted PBHSCT from an HLA-disparate relative is a valuable option for children with hematological malignancies needing an allograft, especially if affected by ALL. Outcome of patients transplanted from an NK-alloreactive donor is very encouraging.