To explore the adverse reactions of unrelated umbilical cord blood stem cell transplantation (CSCT) treatment for bronchopulmonary dysplasia (BPD) of extreme premature infants (EPI) and its related literature review.

Twins of EPI (infant 1: first delivery in twins; infant 2: second delivery in twins) hospitalized in Bayi children′s Hospital Affiliated to the Seventh Medical Center of the General Hospital of the People′s Liberation Army of China, on December 24, 2018, and treated with unrelated umbilical CSCT for BPD, were selected as study objects. The clinical data of EPI twins were analyzed retrospectively, especially focusing on clinical data of unrelated umbilical CSCT, which was operated 31 d after the EPI twins were given birth, including clinical manifestations, adverse reactions, follow-up results and prognoses of the EPI twins. At the same time, literature related to the safety and adverse reactions of CSCT of newborns or children in domestic and foreign databases were searched and reviewed. This study was approved by the Ethics Committee of the General Hospital of the People′s Liberation Army of China (Approval No. 2015111). The family members were informed and agreed to the treatment for each participate of EPI twins.

①EPI twins with BPD were treated by unrelated umbilical CSCT, and their processes were all uneventful. On the second day after CSCT of EPI twins, hematuria, anemia, increase of blood bilirubin value and increase of reticulocyte (Ret) occurred, and based on these symptoms, we considered EPI twins had developed to hemolytic anemia. Routine treatments for hemolytic anemia were performed, including alkalization of urine once and transfusion of isotype suspended red blood cells. The routine blood test of them were normal after 5 days and routine urine test were also normal after 7 days of treatments for hemolytic anemia. The liver and kidney functions were normal, and there were no obvious changes in blood gas analysis between before and after CSCT. Treatment measurement of infant 1 and infant 2 of twins were changed into mixed oxygen inhalation treatment on the 52nd and the 55th day of hospitalization respectively, extra oxygen treatment were stopped on the 72nd and the 78th day of hospitalization respectively, cured and discharged on the 86th and the 122nd day of hospitalization respectively. Followed up to 6 months, the development level of twins reached the level of children with corrected gestational age. Followed up to 1 year and 1 month, there were no significant retardation in growth, movement and language development of twins, and they were continuing to follow up in outpatient department. ②Literature review: the treatment for BPD of premature infants with tracheal mesenchymal stem cells transplantation (MSCT) were well-tolerated. Among them, there were no serious adverse reactions in a short-term, no death within 6 h after MSCT, or anaphylactic shock related to MSCT and dose limiting toxicity occured after treated by MSCT, and 88.9%(8/9) premature infants had good long-term prognoses. Adverse reactions of children treated by CSCT including autoimmune hemolytic anemia (AIHA), autoimmune thrombocytopenic purpura (ATTP), chronic graft versus host disease (cGVHD) and nephrotic syndrome, and the prognoses were good after corresponding treatment.

It was found that the adverse reactions after unrelated umbilical CSCT for BPD of EPI twins were mild and had eusemia with proactively treated.