Program: Oral and Poster Abstracts
Session: 722. Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Prevention
Patients and study design: Included in this analysis were 108 children. Median age at transplant was 5.6 years (range, 0.3-18) and the male/female ratio was 61/47. Patients were subdivided according to the original disorder in 5 groups: group A (53 children with acute leukemia), group B (22 with primary immune-deficiency, PIDs), group C (14 with erythroid disorders), group D (7 with Fanconi anemia) and group E (12 with other diseases). No patient was given any post-transplant graft-versus-host disease (GvHD) prophylaxis. Nine children were enrolled in the phase I portion of the trial consisting of 3 cohorts, receiving escalating doses of BPX-501 cells of 2.5x105, 5x105, and 1x106 cells/kg, respectively. The remaining 99 patients included in the phase II portion received 1x106 BPX-501 cells/kg. Per protocol, BPX-501 cells were to be infused within the first month after αβ haplo-HSCT. We evaluated the absolute number of circulating CD3+, CD3+/CD4+, CD3+/CD8+, CD19+, and NK cells at 1, 2, 3, 6, 9, 12 and 24 months after αβ haplo-HSCT. We also analyzed the number of BPX-501 cells, αβ T cells and γδ T cells at the same time points. The impact of patient gender, age (0-2, 2-6, 6-12 and >12 years), original disease, use of total body irradiation (TBI) during conditioning regimen, occurrence of cytomegalovirus (CMV) reactivation, of acute GvHD and of leukemia relapse (only in group A patients), on recovery of different lymphocyte subsets was investigated, as well. Data were expressed as mean value+SEM (standard error of mean). Six patients given Rimiducid, the agent activating iC9, were censored at time of drug infusion.
Results: After infusion, BPX-501 cells expanded progressively reaching a peak at 9 months after the allograft, when their mean value was 144+36/μL. In the 16 patients with 2-year follow-up, the mean number of BPX-501 cells was still 62+23/μL. Details on expansion/persistence of BPX-501 cells, as well as on recovery of CD3+, CD4+ and CD8+ T cells, are shown in Figure 1A and 1B, respectively. A mean number of CD3+ cells greater than 1.000/μL was reached at 6 months after transplantation. Figure 1C depicts the progressive recovery of B cells. NK and γδ T cells promptly recovered after the allograft; the number of αβ T cells overcomes that of γδ T cells at 2 months after transplant. CMV reactivation promoted a statistically better expansion of BPX-501 cells (see also Figure 1D). This effect was paralleled by an improved recovery of both CD3+ and αβ T cells in patients who experienced CMV reactivation. A statistically higher number of both CD3+ and αβ T cells was observed at 6 and 12 months after αβ haplo-HSCT in patients who did not receive TBI. Neither acute GvHD nor leukemia recurrence occurrence statistically affected the number of BPX-501 cells. Children with an age comprised between 0-2 years or with PIDs had a better recovery of both CD3+ and αβ T cells at 6, 9 and 12 months after the allograft.
Conclusions: Our results indicate that BPX-501 cells infused after αβ haplo-HSCT expand in vivo and persist over time, contributing to fasten adaptive immunity recovery. Their peak of expansion is reached at 9 months after the allograft, but they are consistently detected also at 2 years after infusion. CMV reactivation is the main driver of BPX-501 cell expansion, this finding suggesting that BPX-501 cells cooperate to the viral clearance. Overall, the whole pattern of immune recovery of these 108 children is improved as compared with that of patients given αβ haplo-HSCT without BPX-501 cell infusion.
Disclosures: O'Neill: Bellicum Pharmaceuticals: Other: contractor. Spencer: Bellicum Pharmaceuticals: Employment, Equity Ownership, Other: stockholders . Foster: Bellicum Pharmaceuticals: Employment, Other: stockholders .
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