DISCUSSION
haplo-SCT, tumor, death, Tumor, toxicity, leukemia, toxicities, HHV-6 infection, GvL, infections, encephalopathy, OS, PRES
TUMOR, TUMOR, BACTERIAL INFECTION, LEUKEMIA, DISEASE, INFECTIONS, ENCEPHALOPATHY, RESIDUAL DISEASE, DISEASE, RELAPSE
Treatment of rHR-NB remains challenging with poor survival rates.The use of ex vivo T-cell–depleted haplo-SCT takes advantage of high-dose chemotherapy and NK-mediated alloreactive graft-versus-tumor/leukemia GvL effects. In mismatched SCT, NK-mediated GvL effects reduced the relapse rates in patients with leukemia.Previously, we reported 5-year EFS and OS of 19% and 23%, respectively, in patients with rHR-NB receiving haplo-SCT without antibody treatment, whereas the current trial exhibits 5-year EFS and OS rates of 43% and 53%, respectively.Disease status before immunotherapy and before haplo-SCT influenced prognosis. Patients with CR or PR before immunotherapy had significantly better 5-year EFS and OS than those with NR/MR/PD. Tumor responses were observed in patients with macroscopic residual disease before DB, as demonstrated by an ORR of 51.2%. Of the 43 patients with disease after haplo-SCT, approximately half reduced their tumor load with DB treatment and 35% achieved CR. This is likely due to an interplay between DB, donor-derived effector cells, and CDC.We performed two additional retrospective analyses evaluating factors at diagnosis, at relapse, and those related to haplo-SCT. None of the factors at diagnosis maintained independent prognostic value, likely attributable to the relatively small sample size. One significant factor was The toxicity of haplo-SCT was acceptable with low TRM and aGvHD rates (7.5%), which was lower than that reported after allogeneic SCT with matched donors.Three patients died during DB therapy because of HHV-6 infection, bacterial infection, and PRES. The infections were considered to be associated with intensive pretreatment and SCT. The encephalopathy might have occurred due to a combination of disease-, transplant-, and antibody-related toxicities. Relapse remained the major cause of death with a CI of 49% at 5 years.For further optimization, we suggest replacing the CD3/CD19 depletion by T-cell receptor αβ/CD19-depleted grafts, which results in accelerated immune reconstitution and allows cotransfusion of additional γδT cells with potential antitumor and antiviral activity.In summary, DB therapy after haplo-SCT demonstrated antitumor activity with acceptable toxicity in patients with rHR-NB and was associated with notable EFS and OS among patients who had achieved at least PR with previous therapy. Further prospective and randomized trials are warranted to evaluate the contribution of each component of the approach, and larger cohorts are needed to allow better risk stratification and patient selection.