Safety of Allogenic Human Cord Blood Derived Mononuclear Cells for Extreme Preterms Infants at High Risk of Death: A Descriptive Study

Backgroud Extreme preterm infants are at a high risk for developing preterm complications and death. Despite advances in medical care, many survivors face a lifetime of disability. Objective: To assess the short term safety of and four-year follow-up outcomes of allogenic, human umbilical cord blood (hUCB) derived mononuclear cells(MNCs) infusion to extreme preterm infants with high risk potential of death. Method: This study was a phase I, open-label, single-arm, single-center trial to evaluate the safety of allogenic, hUCB-MNCs infusion for extreme preterm infants with high risk potential of death. HUCB MNCs characteristics, pre- and postinfusion vital signs and laboratory investigations were recorded. Temporal profiles of cytokines and growth factors from blood were test. Clinical data including mortality rates, preterm complications and follow-up outcomes were recorded. Results: After processing, relatively MNCs mean (1.9±0.8) ×10 6 /kg; volume mean (11.25±2.12)ml/kg were infused to 10 extremely preterm infants with high risk of death. No adverse effects were noticed during treatment. 40% received extubation and weaned to nasal CPAP successfully; 30% received lower FiO 2 ; no infants suffered from late onset sepsis; 30% received poor response to MNCs infusion. 40% infants suffered from ROP and only one infant needed laser surgery. No patients suffered from NEC after MNCs infusion. All ten infants who received hUCB MNCs infusion survived inhospital and prevent deterioration of clinical features, but 4 infants discharged against the advice of the doctor by their parents and lost connection. Regarding the rest 6 infants, no home oxygen therapy and rehospitalization, no suffered from other long-term respiratory complications at visit 1～visit 3. One infant showed cerebral palsy at visit 1, no clinical evidence associated this with MNCs infusion. Blood level of HGF significantly increased, but MMP-9, IL-6, IL-8, TNF-α and TGF-β levels were significantly lower at 24h post infusion compared with baseline ( P < 0.05). Conclusions: Collection, preparation, and infusion of allogenic hUCB MNCs to extreme preterm infants is feasible and safe. Trial registration The study was registered on Chinese Clinical Trials.gov (NO. ChiCTR–OPN - 15006932). Registered 17 August 2015, http://www.chictr.org.cn/edit.aspx?pid=11662&htm=4.