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.

Background: We retrospectively analyzed the data of children with non-malignant diseases who have received a haploidentical hematopoietic stem cell transplant (haplo-HSCT). A total of 31 haplo-HSCT were performed in 26 pediatric patients using ex vivo T cell-depleted (TCD) graft platforms or post-transplantation cyclophosphamide (PT-Cy) from January 2001 to December 2016 in 7 Spanish centres. Procedure: A total of five cases were unmanipulated PT-Cy haplo-HSCT, sixteen received highly purified CD34+ cells, ten were ex vivo TCD graft manipulated either with CD3+CD19+ depletion (n= 1), TCΡαβ+CD19+ selection (n= 7) or naive CD45RA+ T cells depletion (n=2). Peripheral blood stem cells were the only source in patients following TCD haplo-HSCT, and bone marrow was the source for one PT-Cy haplo-HSCT. The most common indications for transplant were primary immune deficiency disorders (PIDs) 18, severe aplastic anemia (SAA) 4, osteopetrosis 2 and thalassemia 2. Results: The 1-year cumulative incidence of graft failure was 27.4 %. The 1-year III-IV acute graft versus host disease (aGvHD) and 1-year chronic graft versus host disease (cGvHD) were 34.6% and 16.7% respectively. Besides, the 2-year overall survival (OS) and the 2-year GvHD-free and relapse-free survival (GRFS) were 44.9% for PIDS and 37.6% for the other NMDs. The TRM at day 100 was 30.8%. Conclusions : These results are discouraged and need to be improved to offer a guaranteed treatment for these patients. Improvements will come if procedures are centralized in centres of expertise. The decision between T-cell depletion platforms will depend on the patients’ underlying diseases, comorbidities, and conditioning regimens.

Background: Since the beginning of SARS-CoV-2 pandemic, it has been widely recognized that children and adolescents seem to have milder clinical courses as compared to adult counterparts. However, there is concern that vulnerable collectives including pediatric patients treated for cancer or under immunosuppression may be at higher risk. Methods: We retrospectively collected Spanish COVID-19 cases in children and adolescents with solid and hematological malignancies, non-malignant chronic hematologic conditions, and post allogeneic-stem cell transplantation, from the beginning of the pandemic on January 31 to April 24, 2020. Results: We included 47 cases with RT-PCR positive COVID-19 from 41 centers in Spain, where 97.6% of pediatric patients are treated for cancer. In most cases (76.6%), infection was asymptomatic, or symptoms were mild. Severe illness was observed in 14.9% of cases with respiratory distress and/or hypoxemia, and 8.5% required admission to the PICU. Symptomatic patients received supportive care associated with antiviral and immunomodulatory agents depending upon severity. Anticancer therapy was withhold in the majority of cases during the infection course. Most patients recovered from COVID-19. Two deaths were reported. Conclusion: In our cohort, most children receiving anticancer chemotherapy presented a mild clinical course and had a good outcome. Highly immunosuppressed patients with major comorbidities were at higher risk of severe infections. Among this fragile collective, individualized expert discussion is critical for anti-infectious therapy and appropriate anticancer treatment.