Red blood cell (RBC) transfusions in preterm neonates are associated with retinopathy of prematurity (ROP). BORN is a multicenter randomized trial investigating whether RBC transfusions from cord blood (CB-RBCs) instead of adult donors (A-RBCs) reduce ROP severity (NCT05100212). The study was conducted between December 2021 and November 2024 in 8 hospitals sited in 8 different Italian regions. Extremely low gestational age neonates (ELGANs) were randomized 1:1 to receive A-RBCs (control) or CB-RBCs (intervention) from birth to postmenstrual age (PMA) of 29 + 6 weeks. The main outcome was severe-ROP rate at 40 weeks PMA or discharge. By intention-to-treat-analysis, 56 patients per arm were evaluated: 16 in the control arm and 14 in the intervention arm developed severe ROP (28·6% versus 25·0%, risk difference [RD] −0·03 [95% CI −0·21% to 0·14%]; P = 0·831). Twenty-four (42·8%) patients in the intervention arm received also A-RBCs. Per-protocol-analysis included those patients receiving exclusively the assigned treatment, consisting of 38 ELGANs in the control arm and 17 in the intervention arm, with comparable characteristics. Thirteen ELGANs in the control arm developed severe ROP, and 10 required ROP treatment whilst no patients in the intervention arm developed severe ROP or treatment-requiring ROP (34·2% versus 0%, RD −0·34 [95% CI −0·51% to −0·07%] for severe ROP, P = 0·005, and 26·3% versus 0%, RD −0·28 [95% CI −0·46% to −0·02%] for treatment-requiring ROP, P = 0·022). Twenty-four patients in the control arm and 5 in the intervention arm developed moderate/severe BPD (63·2% versus 29·4%, RD −0·33 [95% CI −0·56% to −0·02%], P = 0·039). CB-RBCs may protect ELGANs from severe forms of ROP and BPD. Funded by Fresenius HemoCare Italia SRL (Prot. N 0038762/21-04/11/2021; grant number 5800134-FPG).
Importance: Repeated transfusions in preterm neonates with anemia of prematurity replace fetal hemoglobin (HbF) with adult Hb (HbA), which has a low oxygen affinity. The reduction of HbF is associated with a higher incidence of retinopathy of prematurity (ROP).Objective: To assess whether HbF and HbA are differently associated with cerebral tissue oxygenation in preterm neonates.Design, Setting, and Participants: This cohort study was a single-center, pilot study on cerebral oxygenation kinetics in preterm neonates with a gestational age between 24.0 weeks and 27.9 weeks who were admitted to the neonatal intensive care unit of Policlinico Universitario A. Gemelli IRCCS from December 27, 2021, to May 15, 2023. This study was ancillary to the ongoing, double-blind, multicenter Umbilical or Adult Donor Red Blood Cells in Extremely Low Gestational Age Neonates and Retinopathy of Prematurity (BORN) randomized clinical trial. The BORN trial outcome was ROP severity in neonates randomized to receive standard packed red blood cell (PRBC) transfusions obtained from RBCs of adult donors (A-RBCs) or from cord blood (CB-RBCs). According to standard procedures at the institute’s neonatal intensive care unit, patients concurrently received continuous cerebral near-infrared spectroscopy (NIRS) monitoring. This cohort study was not prespecified in the trial protocol.Exposure: Transfusion with A-RBCs or CB-RBCs.Main Outcomes and Measures: The main outcome was the kinetics of cerebral regional oxygen saturation (crSO2) and cerebral fraction of tissue oxygen extraction (cFTOE) associated with A-RBC or CB-RBC transfusions. Cerebral NIRS monitoring was performed by neonatologists and nurses, who were blinded to the PRBC type. The NIRS monitoring was conducted starting with the blood product order, during transfusion, and for the subsequent 24 hours after transfusion completion. The mean treatment effects of A-RBCs or CB-RBCs were quantified using a linear mixed model for repeated measures.Results: Of 23 randomized neonates, 17 (11 male [64.7%]; median gestational age at birth, 25.6 weeks [IQR, 25.3-26.1 weeks]) with a median birth weight of 840 g (IQR, 580-900 g) were included in the study; NIRS was evaluated for 42 transfusion episodes, of which 22 were A-RBCs and 20 were CB-RBCs. Globally considering all posttransfusion time points, the overall crSO2 covariate-adjusted mean after CB-RBC transfusions was 5.27% lower (95% CI, 1.20%-9.34%; P = .01) than that after A-RBC transfusions, while the cFTOE after CB-RBC transfusions was 6.18% higher (95% CI, 1.66%-10.69%; P = .009) than that after A-RBCs.Conclusions and Relevance: The findings of this cohort study suggest that A-RBC transfusions may be associated with more oxygen delivery to cerebral tissues of preterm neonates than transfusions from CB-RBCs. This finding may explain the previously observed association between low HbF and high ROP risk. It also suggests that use of CB to meet the RBC transfusion needs of neonates with a gestational age of less than 28 weeks may protect cerebral tissues from overexposure to oxygen.
Transfusion guidelines worldwide include recommendations regarding the storage length, irradiation, or even donor cytomegalovirus serostatus of red blood cell (RBC) units for anemic neonates. Nevertheless, it is totally overlooked that RBCs of these patients fundamentally differ from those of older children and adults. These differences vary from size, shape, hemoglobin composition, and oxygen transport to membrane characteristics, cellular metabolism, and lifespan. Due to these profound dissimilarities, repeated transfusions of adult RBCs in neonates deeply modify the physiology of circulating RBC populations. Unsurprisingly, the number of RBC transfusions in preterm neonates, particularly if born before 28 weeks of gestation, predicts morbidity and mortality. This review provides a comprehensive description of the biological properties of fetal, cord blood, and neonatal RBCs, including the implications that neonatal RBCs, and their replacement by adult RBCs, may have for perinatal disease pathophysiology.
The COVID-19 pandemic has precipitously changed the practice of transplanting fresh allografts. The safety measures adopted during the pandemic prompted the near-universal graft cryopreservation. However, the influence of cryopreserving allogeneic grafts on long-term transplant outcomes has emerged only in the most recent literature. In this review, the basic principles of cell cryopreservation are revised and the effects of cryopreservation on the different graft components are carefully reexamined. Finally, a literature revision on studies comparing transplant outcomes in patients receiving cryopreserved and fresh grafts is illustrated.
Patients affected by transfusion-dependent β-thalassemia are prone to developing several clinical complications, mostly related to the iron overload. We report the case of a patient affected by transfusion-dependent β-thalassemia (TDT) developing acute promyelocytic leukemia (APL). In our case, the therapeutic management was significantly complicated not only by myocardial dysfunction, but also by the occurrence of the differentiation syndrome following all-trans retinoic acid (ATRA) administration. We carried out a careful revision of the current literature on the occurrence of hematological malignancies in β-thalassemia patients to investigate the major complications so far described. APL occurrence in β-thalassemia patients has been very rarely reported, and our experience suggests that TDT patients suffering pre-existing comorbidities may develop a potentially fatal complication during ATRA therapy.
Plerixafor is widely used as up-front treatment with G-CSF to enhance peripheral blood hematopoietic stem cell output in patients failing previous mobilizations. Less frequently, plerixafor is used to rescue an unsatisfactory mobilization following chemotherapy (CT) and G-CSF. This study investigates if pre-collection factors affect the CD34+ cell harvest in chemotherapy and G-CSF mobilizations rescued by plerixafor. Clinical and hematological data relative to patients, mobilization, and apheresis products were retrospectively examined. The outcome was completing a target cell dose ≥ 2 × 106 CD34+ cells/kg at first apheresis. The effect exerted on the outcome by patient- and disease-related factors was investigated by univariate and multivariate logistic regression analysis. The analysis included data from 42 patients affected by hematological (39 patients) and non-hematological malignancies (three patients). Twenty-nine patients (69%) attained the target cell dose at first apheresis. Twelve out of the remaining 13 patients received an additional plerixafor administration, and all accomplished the transplant dose at a second apheresis procedure. Day -1 CD34+ PB count (OR1.46, 95% CI 1.1–1.9, p = 0.008) and platelet count (OR1.0, 95% CI 1.0–1.0, p = 0.033) predicted the achievement of the target dose at first apheresis, independently of pre-mobilization CT, radiation therapy, and disease status at mobilization. At ROC curve analysis, the best cut-off value predicting the successful collection at first apheresis was 7.5/µL for Day -1 CD34+ cell count (AUC 0.830, 0.69 sensitivity, and 0.92 specificity) and 75 × 109/L for Day -1 platelet count (AUC = 0.736, 0.65 sensitivity and 0.85 specificity). In conclusion, on-demand plerixafor rescue allows a successful stem cell collection, irrespectively of disease type and status, prior CT lines, and radiation exposure. Pre-apheresis CD34+ cells and platelet count predict the need for one or two aphereses.