Effect of umbilical cord blood-mononuclear cells on knee osteoarthritis in rabbits.

BACKGROUND: To investigate the effect and underlying mechanism of umbilical cord blood-mononuclear cells (UCB-MNCs) in treating knee osteoarthritis (KOA) in rabbits. METHODS: A rabbit KOA model was prepared by anterior cruciate ligament transection (ACLT). Fifty New Zealand white rabbits were randomly divided into the control group, model group, sodium hyaluronate (SH) group, platelet-rich plasma (PRP) group and UCB-MNC group. Knee injections were performed once a week for five consecutive weeks. The gross view of the knee joint, morphology of knee cartilage and structural changes in the knee joint were observed on CT scans, and graded by the Lequesne MG behavioral score and the Mankin score. TNF-α and IL-1ß levels in the synovial fluid of the knee were measured by the enzyme-linked immunosorbent assay (ELISA). Expression levels of MMP-13 and COL-II in the knee cartilage were detected by Western blotting and qRT-PCR. RESULTS: The Lequesne MG behavioral score and the Mankin score were significantly higher in the model group than those in the control group (P < 0.05). Rabbits in the SH, PRP and UCB-MNC groups had sequentially lower scores than those in the model group. Imaging features of KOA were more pronounced in the model group than in the remaining groups. CB-MNC significantly relieved KOA, compared to SH and PRP. Significantly higher levels of TNF-α and IL-1ß in the synovial fluid of the knee, and up-regulated MMP-13 and down-regulated COL-II in the knee cartilage were detected in the model group than in the control group. These changes were significantly reversed by the treatment with SH, PRP and UCB-MNCs, especially UCB-MNCs. CONCLUSION: Injections of UCB-MNCs into knees protect the articular cartilage and hinder the progression of KOA in rabbits by improving the local microenvironment at knee joints.

Early administration of umbilical cord blood cells following brief high tidal volume ventilation in preterm sheep: a cautionary tale.

BACKGROUND: Umbilical cord blood (UCB) cells are a promising treatment for preterm brain injury. Access to allogeneic sources of UCB cells offer the potential for early administration to optimise their therapeutic capacities. As preterm infants often require ventilatory support, which can contribute to preterm brain injury, we investigated the efficacy of early UCB cell administration following ventilation to reduce white matter inflammation and injury. METHODS: Preterm fetal sheep (0.85 gestation) were randomly allocated to no ventilation (SHAM; n = 5) or 15 min ex utero high tidal volume ventilation. One hour following ventilation, fetuses were randomly allocated to i.v. administration of saline (VENT; n = 7) or allogeneic term-derived UCB cells (24.5 ± 5.0 million cells/kg; VENT + UCB; n = 7). Twenty-four hours after ventilation, lambs were delivered for magnetic resonance imaging and post-mortem brain tissue collected. Arterial plasma was collected throughout the experiment for cytokine analyses. To further investigate the results from the in vivo study, mononuclear cells (MNCs) isolated from human UCB were subjected to in vitro cytokine-spiked culture medium (TNFα and/or IFNγ; 10 ng/mL; n = 3/group) for 16 h then supernatant and cells collected for protein and mRNA assessments respectively. RESULTS: In VENT + UCB lambs, systemic IFNγ levels increased and by 24 h, there was white matter neuroglial activation, vascular damage, reduced oligodendrocytes, and increased average, radial and mean diffusivity compared to VENT and SHAM. No evidence of white matter inflammation or injury was present in VENT lambs, except for mRNA downregulation of OCLN and CLDN1 compared to SHAM. In vitro, MNCs subjected to TNFα and/or IFNγ displayed both pro- and anti-inflammatory characteristics indicated by changes in cytokine (IL-18 & IL-10) and growth factor (BDNF & VEGF) gene and protein expression compared to controls. CONCLUSIONS: UCB cells administered early after brief high tidal volume ventilation in preterm fetal sheep causes white matter injury, and the mechanisms underlying these changes are likely dysregulated responses of the UCB cells to the degree of injury/inflammation already present. If immunomodulatory therapies such as UCB cells are to become a therapeutic strategy for preterm brain injury, especially after ventilation, our study suggests that the inflammatory state of the preterm infant should be considered when timing UCB cells administration.

Designer umbilical cord-stem cells induce alveolar wall regeneration in pulmonary disease models.

Background: Researchers are focusing on cellular therapy for chronic obstructive pulmonary disease (COPD) using mesenchymal stem cells (MSCs), with human bone marrow-derived MSCs (hBM-MSCs) leading the way. However, BM-MSCs may not be as optimal as therapeutic cells owing to their low growth potential, invasive harvesting, and high expression of aging-related genes with poor differentiation potential. Consequently, umbilical cord-derived MSCs (hUC-MSCs), which have many excellent features as allogeneic heterologous stem cells, have received considerable attention. Allogeneic and heterologous hUC-MSCs appear to be promising owing to their excellent therapeutic properties. However, MSCs cannot remain in the lungs for long periods after intravenous infusion. Objective: To develop designer hUC-MSCs (dUC-MSCs), which are novel therapeutic cells with modified cell-adhesion properties, to aid COPD treatment. Methods: dUC-MSCs were cultured on type-I collagen gels and laminin 411, which are extracellular matrices. Mouse models of elastase-induced COPD were treated with hUC-MSCs. Biochemical analysis of the lungs of treated and control animals was performed. Results: Increased efficiency of vascular induction was found with dUC-MSCs transplanted into COPD mouse models compared with that observed with transplanted hUC-MSCs cultured on plates. The transplanted dUC-MSCs inhibited apoptosis by downregulating pro-inflammatory cytokine production, enhancing adhesion of the extracellular matrix to alveolar tissue via integrin ß1, promoting the polarity of M2 macrophages, and contributing to the repair of collapsed alveolar walls by forming smooth muscle fibers. dUC-MSCs inhibited osteoclastogenesis in COPD-induced osteoporosis. hUC-MSCs are a promising cell source and have many advantages over BM-MSCs and adipose tissue-derived MSCs. Conclusion: We developed novel designer cells that may be involved in anti-inflammatory, homeostatic, injury repair, and disease resistance processes. dUC-MSCs repair and regenerate the alveolar wall by enhancing adhesion to the damaged site. Therefore, they can contribute to the treatment of COPD and systemic diseases such as osteoporosis.

Effect of IL-2 polymorphism rs2069762 on single-unit cord blood transplant outcomes.

BACKGROUND: Interleukin-2 (IL-2) is one of the most important cytokines that regulate the activation and proliferation of T cells and natural killer cells. The production of IL-2 may be affected by polymorphisms in the promoter region of the IL-2 gene (rs2069762). In allogeneic hematopoietic cell transplantation (HCT) from adult donors, rs2069762 has been associated with the incidence of acute and chronic graft-versus-host disease (GVHD). However, the impacts of IL-2 polymorphism on cord blood transplantation (CBT) outcomes remain unclear. OBJECTIVE: The objective of this study was to assess the impact of IL-2 polymorphism rs2069762 on transplant outcomes, such as hematopoietic recovery, GVHD, overall survival, relapse, and non-relapse mortality (NRM) after CBT. STUDY DESIGN: We conducted a retrospective analysis of data from adult patients who underwent single-unit CBT at our institution from November 2005 to March 2023 for whom DNA samples from recipients and donors were available. IL-2 genotyping was performed using real-time polymerase chain reaction with the TaqMan® SNP genotyping assay for rs2069762. RESULTS: A total of 143 recipient and donor pairs were included in this study. The proportion of recipient IL-2 polymorphism rs2069762 was 48 % (n = 69) for AA, 42 % (n = 60) for CA, and 10 % (n = 14) for CC. The proportion of donor IL-2 polymorphism rs2069762 was 43 % (n = 61) for AA, 48 % (n = 69) for CA, and 9 % (n = 13) for CC. In the multivariate analysis, the use of an rs2069762 CA + CC donor was associated with lower neutrophil recovery compared to an rs2069762 AA donor (hazard ratio [HR], 0.66; 95 % confidence interval [CI], 0.50-0.88; P = 0.004). Furthermore, recipients of rs2069762 CA + CC were associated with higher NRM compared to recipients of rs2069762 AA (HR, 2.32; 95 % CI, 1.01-5.34; P = 0.047). Serum IL-2 levels at 8 weeks were significantly higher in rs2069762 CA + CC recipients compared to those with rs2069762 AA recipients (P = 0.014). CONCLUSION: Our data showed that donor IL-2 polymorphism affects neutrophil recovery and recipient IL-2 polymorphism affects NRM in adults undergoing single-unit CBT. The polymorphism of IL-2 rs2069762 in recipients and donors might be associated with the clinical outcomes of single-unit CBT.

[Analysis of efficacy and prognosis of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency].

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency (CID) and explore prognostic risk factors. Methods: In this retrospective cohort study, clinical characteristics, laboratory tests and prognosis of 73 CID children who underwent allogeneic hematopoietic stem cell transplantation from February 2014 to April 2022 in the Children's Hospital of Fudan University were analyzed. Based on the subtypes of diseases, all patients were divided into severe combined immunodeficiency disease (SCID) group and other CID group. Based on the types of donors, all patients were divided into matched sibling donor group, matched unrelated donor group, unrelated cord blood group, and haploidentical donor group. Kaplan-Meier method and Log-Rank test were used to analyze the survival data. Cox regression was used to analyze prognostic factors. Results: Among the 73 patients, there were 61 (84%) males and 12 (16%) females. Fifty-five (75%) patients were SCID, and 18 (25%) patients were other CID. Donor source included 2 (3%) matched sibling donors (MSD), 3 (4%) matched unrelated donors (MUD), 64 (88%) unrelated cord blood (UCB), and 4 (5%) haploidentical donors. The age at transplant was 10.7 (5.9, 27.5) months, and the follow-up time was 36.2 (2.5, 62.9) months. The 3-year overall survival rate of 73 patients with CID was (67±6) %. No significant difference was found in the 3-year overall survival rates between patients with SCID (55 cases) and other CID (18 cases) ((64±7) % vs. (78±10) %, χ2=1.31, P=0.252). And no significant difference was found in the 3-year overall survival rates among patients who received MSD or MUD (5 cases), UCB (64 cases), and haploidentical donor (4 cases) transplant (100% vs. (66±6)% vs. (50±25) %, χ2=2.30, P=0.317). Cox regression analysis showed that the medical history of sepsis (HR=2.55, 95%CI 1.05-6.20, P=0.039) and hypoalbuminemia at transplant (HR=2.96, 95%CI 1.14-7.68, P=0.026) were independent risk factors for the prognosis of allogeneic hematopoietic stem cell transplantation in pediatric patients with CID. Conclusions: Allogeneic hematopoietic stem cell transplantation is an effective treatment for CID. The medical history of sepsis and hypoalbuminemia at transplant were risk factors for prognosis. Enhancing infection prevention and nutritional intervention before transplant can improve patient prognosis.

The fulfilled promise and unmet potential of umbilical cord blood.

PURPOSE OF REVIEW: Here, we review classic and emerging uses of umbilical cord blood and highlight strategies to improve its utility, focusing on selection of the appropriate units and cell types for the intended applications. RECENT LITERATURE: Recent studies have shown advancements in cord blood cell utility in a variety of cellular therapies and have made strides in elucidating manners to select the best units for therapy and target new ways to improve the various cell subpopulations for their respective applications. SUMMARY: Umbilical cord blood is a proven source of cells for hematopoietic cell transplantation and research and is an important potential source for additional cellular therapies. However, cord blood utility is limited by low "doses" of potent cells that can be obtained from individual units, a limitation that is specific to cord blood as a donor source. In addition to traditional CD34 + progenitor cells, cord blood lymphocytes are being pursued as therapeutic entities with their own unique properties and characteristics. Thus, selection of ideal units depends on the intended therapeutic entity and target, and identification of differential potency parameters is critical to drive effective banking strategies accommodating successful clinical use of cord blood in broader cell therapy settings.

High-dose individualized antithymocyte globulin with therapeutic drug monitoring in high-risk cord blood transplant.

BACKGROUND: Graft-versus-host disease (GvHD) and rejection are main limitations of cord blood transplantation (CBT), more so in patients with severe inflammation or previous rejections. While rigorous T-cell depletion with antithymocyte globulin (ATG) is needed to prevent GvHD and rejection, overexposure to ATG leads to slow T-cell recovery after transplantation, especially in CBT. OBJECTIVE: To evaluate high-dose, upfront ATG with individualized dosing and therapeutic drug monitoring (TDM) in pediatric CBT for patients at high risk for GvHD and rejection. STUDY DESIGN: Heavily inflamed patients and patients with a recent history of rejection were eligible for individualized high-dose ATG with real-time TDM. The ATG dosing scheme was adjusted to target a post-CBT exposure of <10 AU*day/mL, while achieving a pre-CBT exposure of 60-120 AU*day/mL; exposure levels previously defined for optimal efficacy and safety in terms of reduced GvHD and rejection, respectively. Main outcomes of interest included efficacy (target exposure attainment) and safety (incidence of GvHD and rejection). Other outcomes of interest included T-cell recovery and survival. RESULTS: Twenty-one patients were included ranging from 2 months to 18 years old, receiving an actual median cumulative dose of ATG of 13.3 mg/kg (range 6-30 mg/kg) starting at a median 15 days (range 12-17) prior to CBT. Dosing was adjusted in 14 patients (increased in 3 and decreased in 11 patients). Eighteen (86%) and 19 (91%) patients reached the target pre-CBT and post-CBT exposure, respectively. Cumulative incidence for acute GvHD was 34% (95% CI 23-45) and 5% (95% CI 0-10%) for grade 2-4 and grade 3-4, respectively; cumulative incidence of rejection was 9% (95% CI 2-16%). Overall survival was 75% (95% CI 65-85%). CONCLUSION: Individualized high-dose ATG with TDM is feasible and safe for patients with hyperinflammation in a CBT setting. We observe high target ATG exposure attainment, good immune reconstitution (despite very high doses of ATG) and acceptable rates of GvHD and rejection.

Machine Learning Prediction Model for Neutrophil Recovery after Unrelated Cord Blood Transplantation.

Delayed neutrophil recovery is an important limitation to the administration of cord blood transplantation (CBT) and leaves the recipient vulnerable to life-threatening infection and increases the risk of other complications. A predictive model for neutrophil recovery after single-unit CBT was developed by using a machine learning method, which can handle large and complex datasets, allowing for the analysis of massive amounts of information to uncover patterns and make accurate predictions. Japanese registry data, the largest real-world dataset of CBT, was selected as the data source. Ninety-eight variables with observed values for >80% of the subjects known at the time of CBT were selected. Model building was performed with a competing risk regression model with lasso penalty. Prediction accuracy of the models was evaluated by calculating the area under the receiver operating characteristic curve (AUC) using a test dataset. The primary outcome was neutrophil recovery at day (D) 28, with recovery at D14 and D42 analyzed as secondary outcomes. The final cord blood engraftment prediction (CBEP) models included 2991 single-unit CBT recipients with acute leukemia. The median AUC of a D28-CBEP lasso regression model run 100 times was .74, and those for D14 and D42 were .88 and .68, respectively. The predictivity of the D28-CBEP model was higher than that of 4 different legacy models constructed separately. A highly predictive model for neutrophil recovery by 28 days after CBT was constructed using machine learning techniques; however, identification of significant risk factors was insufficient for outcome prediction for an individual patient, which is necessary for improving therapeutic outcomes. Notably, the prediction accuracy for post-transplantation D14, D28, and D42 decreased, and the model became more complex with more associated factors with increased time after transplantation.

Long-term lymphocyte subset number reconstitution is unique but comparable between umbilical cord blood and unrelated bone marrow transplantation.

The number of umbilical cord blood transplantation (U-CBT) procedures has been growing annually, but little research has been done on long-term immune recovery after U-CBT. Infection risk is high in U-CBT recipients, and this can be partially attributed to immature immunocompetent cells in umbilical cord blood. In this study, we analyzed lymphocyte subset (LST) number to determine the long-term recovery timeline. We included 36 U-CBT and 10 unrelated bone marrow transplantation (U-BMT) recipients who survived more than 2 years after transplantation, and followed them for up to 10 years post-transplant. Recovery kinetics in the early phase post-transplant was different for each LST. Recovery of CD19+ B cells was faster after U-CBT than after U-BMT in the first 5 years after transplantation. Although CD4+ T cells increased in the first several months after U-CBT, long-term cell count recovery was impaired in approximately 20% of patients. Thus, although the LST recovery pattern after U-CBT was unique, LST number recovery was statistically comparable between U-CBT and U-BMT past 5 years post-transplantation.

First complete remission favours haploidentical haematopoietic stem cell transplantation with post-transplant cyclophosphamide over cord blood transplantation in acute lymphoblastic leukaemia.

To assess the benefits of HLA-haploidentical haematopoietic stem cell transplantation using post-transplant cyclophosphamide (PTCy-haplo) relative to those of umbilical cord blood (UCB) transplantation in acute lymphoblastic leukaemia (ALL), we analysed 1999 patients (PTCy-haplo, 330; UCB, 1669), using the nationwide Japanese registry. PTCy-haplo was associated with a significantly higher relapse rate, but lower non-relapse mortality, which results in overall survival and disease-free survival, comparable to those of UCB. Among patients in CR1, PTCy-haplo showed a significantly higher survival than UCB regardless of the CD34+ cell dose. Our findings provide valuable insights into the donor selection algorithm in allogeneic HSCT for adult patients with ALL.

Development of an umbilical cord blood transplantation-specific nonrelapse mortality risk assessment score.

ABSTRACT: Higher rate of nonrelapse mortality (NRM) remains yet to be resolved in umbilical cord blood transplantation (UCBT). Considering that UCBT has some unique features compared with allogeneic hematopoietic cell transplantation from other graft sources, a UCBT-specific NRM risk assessment system is required. Thus, in this study, we sought to develop a UCBT-specific NRM Risk Assessment (CoBRA) score. Using a nationwide registry database, we retrospectively analyzed 4437 recipients who had received their first single-unit UCBT. Using the backward elimination method, we constructed the CoBRA score in a training cohort (n = 2687), which consisted of recipients age ≥55 years (score 2), hematopoietic cell transplantation-specific comorbidity index ≥3 (score 2), male recipient, graft-versus-host disease prophylaxis other than tacrolimus in combination with methotrexate, performance status (PS) 2 to 4, HLA allele mismatch ≥ 2, refined Disease Risk Index high risk, myeloablative conditioning, and CD34+ cell doses < 0.82 × 105/kg (score 1 in each). The recipients were categorized into 3 groups: low (0-4 points), intermediate (5-7 points), and high (8-11 points) groups according to the CoBRA score. In the validation cohort (n = 1750), the cumulative incidence of NRM at 2 years was 14.9%, 25.5%, and 47.1% (P < .001), and 2-year overall survival (OS) was 74.2%, 52.7%, and 26.3% (P < .001) in the low, intermediate, and high groups, respectively. In summary, the CoBRA score could predict the NRM risk as well as OS after UCBT. Further external validation will be needed to confirm the significance of the CoBRA score.

Long-Term Stability of Cord Blood Units After 29 Years of Cryopreservation: Follow-Up Data From the José Carreras Cord Blood Bank.

The José Carreras Cord Blood Bank (CBB) located in Düsseldorf as of today stores 21 215 active cryopreserved cord blood units (CBUs) applicable as a source for hematopoietic stem cell (HSC) transplantation. Since the success of transplantation outcomes is mainly dependent on the cord blood quality, typical parameters are evaluated by a Stability Monitoring Program specified by the FACT Standards. The longest expiration time determined to date is 29 years for unseparated units, 25 years for manual and 18 years for automated volume-reduced units licensed by the Paul-Ehrlich Institute. According to the CBB stability program TNC count, TNC recovery, TNC viability, CD34+7AAD- viability, CD45+7AAD- viability and CFC count were determined for all 3 processing methods applied over time. As a measure of stability, unseparated units (processed 1993-1998) revealed a mean TNC viability of 88.91 ±â€…5.01% after 29 years of cryopreservation versus manual volume-reduced CBUs (processed 1998-2005) with a mean of 84.22 ±â€…10.02% after 25 years of cryopreservation versus automated volume-reduced CBUs (processed since 2005) with a mean of 88.64.91 ±â€…3.91% after 18 years of cryopreservation. In addition, these relevant parameters were retrospectively analyzed for released transplants in correlation to the storage time. Moreover, the follow-up data of recipients from CBUs cryopreserved directly (unseparated) versus CBUs cryopreserved after manual versus automated volume-reduction are presented here demonstrating an earlier engraftment in both volume-reduced groups as compared to unseparated CBUs. By this retrospective analysis, key questions are discussed regarding cord blood parameters in relation to processing methods, engraftment, and patient age (children and adults).

The therapeutic role of SSEA3(+) human umbilical cord blood mononuclear cells in ischemic stroke model.

Numerous evidences showed that human umbilical cord blood (UCB) mononuclear cells were a promising approach for the therapy of ischemic stroke(IS). The effect of stage-specific embryonic antigen 3 (SSEA3）positive subpopulation in UCB was not investigated in IS. In this study, we isolated SSEA3 positive cells from healthy UCB mononuclear cells, which comprised about 7.01% of the total UCB-mononuclear cells. Flow cytometry analysis revealed that SSEA3(+)UCB cells were almost positive for CD44 and CD45, and negative for CD73, CD90 and CD105. The expression of Oct3/4 in SSEA3(+)UCB cells were higher than that in UCB. SSEA3(+)UCB cells sorted by magnetic cell sorting were intravenously injected into the middle cerebral arterial occlusion(MCAO) rat model. Neurological score showed that SSEA3(+)UCB transplantation group exhibited significant improvements in the functional outcome of MCAO rats than UCB transplantation group. Nissl staining and microtubule association protein-2(MAP2) immunofluorescence staining showed that the SSEA3(+)UCB transplantation group decreased neuronal loss. SSEA3(+)UCB transplantation group reduced neuronal apoptosis, inhibited caspase3 expression, and decreased tumor necrosis factor α(TNF-α). These results indicate that SSEA3 positive cells are a novel subpopulation of UCB cells, which exhibit great potential for the treatment of ischemic stroke.

A predictive model combining clinical characteristics and nutritional risk factors for overall survival after umbilical cord blood transplantation.

BACKGROUND: Umbilical cord blood transplantation (UCBT) is a curable therapy for hematological disease; however, the impact of nutritional status on UCBT outcomes remains controversial. To evaluate the joint effect of clinical characteristics and nutritional status on the prognosis of patients who underwent UCBT, we screened various factors to establish a predictive model of overall survival (OS) after UCBT. METHODS: We performed an integrated clinical characteristic and nutritional risk factor analysis and established a predictive model that could be used to identify UCBT recipients with poor OS. Internal validation was performed by using the bootstrap method with 500 repetitions. RESULTS: Four factors, including disease status, conditioning regimen, calf skinfold thickness and albumin level, were identified and used to develop a risk score for OS, which showed a positive predictive value of 84.0%. A high-risk score (≥ 2.225) was associated with inferior 3-year OS post-UCBT [67.5% (95% CI 51.1-79.4%), P = 0.001]. Then, we built a nomogram based on the four factors that showed good discrimination with a C-index of 0.833 (95% CI 0.743-0.922). The optimism-corrected C-index value of the bootstrapping was 0.804. Multivariate analysis suggested that a high calf skinfold thickness (≥ 20.5 mm) and a low albumin level (< 33.6 g/L) conferred poor disease-free survival (DFS). CONCLUSION: The predictive model combining clinical and nutritional factors could be used to predict OS in UCBT recipients, thereby promoting preemptive treatment.

Progress in the treatment of neonatal hypoxic-ischemic encephalopathy with umbilical cord blood mononuclear cells.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a common disease among newborns, which is a leading cause of neonatal death and permanent neurological sequelae. Therapeutic hypothermia (TH) is the only method for the treatment of HIE that has been recognized effective clinically at home and abroad, but the efficacy is limited. Recent research suggests that the cord blood-derived mononuclear cells (CB-MNCs), which the refer to blood cells containing one nucleus in the cord blood, exert anti-oxidative, anti-inflammatory, anti-apoptotic effects and play a neuroprotective role in HIE. This review focuses on safety and efficacy, the route of administration, dose, timing and combination treatment of CB-MNCs in HIE.

Side Effects After Use of Bedside Thaw Method for Umbilical Cord Blood Stem Cell Allogeneic Transplantations in a Pediatric Cohort: A Single-center Experience.

BACKGROUND AND OBJECTIVES: Several strategies and procedures have been described for thawing umbilical cord blood (UCB) products. The ideal method for each center depends on the resources, staff training, and access to each of these. We retrospectively evaluated the incidence of side effects using the bedside thaw method after unrelated UCB transplantation. PATIENTS AND METHODS: For 34 children, patient, donor, graft characteristics, and side effects were identified. In addition, we attempted to identify the risk factors that could be associated with side effects. RESULTS: 68% of patients experienced any adverse reaction. All the reactions were mild and transient events. The most frequent side effects were vomiting, hypertension, hemolytic reactions, and fever. There were more gastrointestinal events with a faster infusion rate. CONCLUSION: The thawed at the bedside method is a practical, easy, and safe technique for cord blood transplantation in pediatric-patient settings.

Impact of allele-level HLA matching on outcomes after double cord blood transplantation in adults with malignancies.

In single unrelated cord blood transplantation (UCBT), an increasing number of HLA allele mismatches (MM) has been associated with inferior overall survival (OS) and attributed to higher transplant-related mortality (TRM). Previous studies on the role of allele-level HLA matching after double UCBT (dUCBT) showed conflicting results. In this study, we report the impact of allele-level HLA matching on the outcomes of a large dUCBT cohort. We included 963 adults with hematologic malignancies, with available allele-level HLA matching at HLA-A, -B, -C, and -DRB1, receiving dUCBT between 2006 to 2019. Assignment of donor-recipient HLA match was performed considering the unit with the highest disparity with the recipient. Three hundred ninety-two patients received dUCBT with 0 to 3 MM and 571 with ≥4 allele MM. For recipients of dUCBT with 0 to 3 MM, day-100 and 4-year TRM were 10% and 23%, respectively, compared with 16% and 36% for those with ≥4 MM. A higher degree of allele MM was also associated with the worse neutrophil recovery and lower incidence of relapse; no significant effect on graft-versus-host disease was observed. Patients receiving units with 0 to 3 MM had a 4-year OS of 54% compared with 43% for those receiving units with ≥4 MM. The inferior OS associated with higher HLA disparity was only partially mitigated by increased total nucleated cell doses. Our results confirm that allele-level HLA typing is a significant factor for OS after dUCBT, and units with ≥4 MM (≤4/8 HLA-matched) should be avoided if possible.

Effect of nutritional status on outcomes in children receiving umbilical cord blood stem cell transplantation.

BACKGROUND AND OBJECTIVES: The impacts of nutritional status on clinical outcomes in children receiving umbilical cord blood stem cell transplantation (UCBT) are not fully described. We evaluated the risk for malnutrition before transplantation admission and influence of weight loss during hospitalization on short-term clinical outcomes in children with UCBT. METHODS AND STUDY DESIGN: We conducted a retrospective study of pediatric patients up to age 18 years who received UCBT and were treated at the Children's Hospital of Fudan University between January 2019 and December 2020. RESULTS: The mean age of the 91 patients was 1.3 years, with 78 (85.7%) men and 13 (14.3%) women (p<0.001). UCBT was performed mostly for primary immunodeficiency disease (PID) (83, 91.2%). The weight loss differences among children with different primary diseases were statistically significant (p=0.003). Children with a large amount of weight loss during hospitalization (n = 24) had higher risks of skin graft-versus-host disease (GVHD) (multivariate OR=5.01, 95% CI: 1.35-18.65), intestinal GVHD (multivariate OR=7.27, 95% CI: 1.74-30.45), a longer median hospital stay (p=0.004), higher antibiotic costs (p=0.008) and higher total hospitalization costs (p=0.004). Malnutrition on admission was significantly positively correlated with longer parenteral nutrition (PN) time (p=0.008). Early nutritional intervention effects on clinical outcomes need further assessment. CONCLUSIONS: Underweight recipient child and excessive weight loss during transplantation increases the length and cost of hospital stay, and is associated with a high incidence of GVHD, which affects the prognosis of transplantation and medical resources consumption.