Allogeneic hematopoietic stem cell transplantation with the modified myeloablative conditioning regimen for children with chronic active Epstein–Barr virus infection

Importance:Allogeneic hematopoietic stem cell transplantation(alloHSCT)is considered the only effective treatment for chronic active Epstein–Barr virus infection(CAEBV).The clinical efficacy and safety of allo-HSCT with different conditioning regimens in children with CAEBV remain unclear.Objective:To evaluate the effectiveness and safety of allo-HSCT with the modified myeloablative conditioning(MAC)regimen for children with CAEBV and also the factors affecting the outcomes.Methods:We retrospectively analyzed children with CAEBV who underwent allo-HSCT with the modified MAC regimen at Beijing Children’s Hospital,Capital Medical University from October 2016 to June 2021.Data related to the clinical manifestations,engraftment,and outcome were extracted from the medical records.Results:The cohort comprised 41 patients(24 males,17 females)with a median transplantation age of 92.6(60.4,120.7)months and a median follow-up time of 28.2(15.3,40.2)months.Four patients(9.8%)died,among which three died from primary disease relapse,and one died from grade IV acute graft-versus-host diseases(aGVHD)after stopping treatment.The 3-year overall survival(OS)and 3-year event-free survival(EFS)rates were 88.8%±5.4%and 85.0%±5.7%,respectively.The 3-year OS and EFS did not significantly differ between the patients with hemophagocytic lymphohistiocytosis(HLH)and the patient without HLH(87.7%±6.8%vs.91.7%±8.0%,P=0.790;85.0%±6.9%vs.84.6%±10.0%,P=0.921),or among the patients with complete remission,partial remission,and activity disease before HSCT(all P>0.05).Multivariate analysis showed that grade III–IV aGVHD was a risk factor for mortality(Hazards ratio:11.65,95%confidence interval:1.00,136.06;P=0.050).Interpretation:Allo-HSCT with the modified MAC regimen is safe and effective for pediatric CAEBV.This treatment benefits patients with HLH or active disease.Patients with Grade III–IV aGVHD may be associated with worse outcomes.

Pediatric cancer surveillance in China:A hospital-based introduction

Background In recent years,increasing numbers of families have been affected by childhood cancer.According to data from the International Agency for Research on Cancer(IARC)of the World Health Organization,approximately 279000 new cases of cancer were predicted in children and adolescents aged 0–19 years worldwide in 2020.The global incidence of childhood cancer is 10.9 per 100000(global standard rate)and the mortality rate is 4.2 per 100000.1 According to data from the China National Cancer Center,the incidences of cancer in 2017 were 9.9 per 100000 in children aged 0–14 years and 11.5 per 100000 in adolescents aged 15–19 years.2 There are estimated to be approximately 22000 new cases of childhood cancer in China each year,and the incidence of malignant tumors in children aged 0–14 years has increased by 2.5%annually in the past decade.

Haploidentical hematopoietic stem cell transplantation using reduced-intensity conditioning for pediatric patients with familial hemophagocytic lymphohistiocytosis

Importance: Allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be the only curative treatment for familial hemophagocytic lymphohistiocytosis (FHLH). Treatment of pediatric FHLH with reduced-intensity conditioning (RIC)-based haploidentical donor (HID) HSCT has been rarely reported. Objective: To investigate outcomes and adverse events in patients with FHLH who received HID-HSCT. Methods: We conducted a retrospective study of five patients, including three with mutations in PRF1 and two with XIAP deficiency. Four of the five donors were heterozygous for these mutations. The conditioning regimen included fludarabine, cyclophosphamide, and antithymocyte globulin, with or without low-dose irradiation. Unmanipulated mobilized bone marrow and peripheral blood stem cells were used as the grafts. results: All five patients were successfully engrafted. Four patients survived, and one patient died. All exhibited complete response (CR) after HSCT. All of the patients who survived exhibited CR to FHLH without severe regimen-related complications at a median of 29.5 months (range: 23–34 months) after HSCT. Four of the five patients had mixed donor chimerism. Three patients had 17% to 87% mixed donor chimerism but remained free of disease. Four patients received donor lymphocyte infusion (DLI), which improved the level of mixed donor chimerism. One patient experienced a decrease in donor chimerism to 1% and relapsed;Four patients developed acute graft-versus-host disease (GvHD) (grade I or II), and one patient developed grade IV GvHD. Interpretation: HID-HSCT with RIC can be considered for treatment for patients with FHLH, but the conditions and DLI regimens need to be optimized for long-term use, and more prospective studies should be conducted.

Variable clinical manifestations of hematopoietic stem cell transplant-associated thrombotic microangiopathy

INTRODUCTIONTransplantation-associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic stem cell transplantation (HSCT) characterized by small vessel endothelial damage leading to thrombosis and fibrin deposition resulting in hemolytic anemia and thrombocytopenia. The severity of TA-TMA varies from mild self-limited disease to a fulminant variant resulting in death. Here, we review two rare cases and review the literature of TA-TMA.