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Several studies have focused on umbilical cord-derived mesenchymal stem cells (UC-MSCs) due to their potential therapeutic effects in a cluster of diseases. However, there has been no bibliometric analysis evaluating the evolution in UC-MSC research. Therefore, this study aimed to assess scientific activity regarding UC-MSC research. Publications on UC-MSCs were retrieved from the Science Citation Index-Expanded (SCI-E) of the Web of Science (WoS) from 1975 to 2017. Statistical analyses were performed using Excel, GraphPad Prism 5, and VOSviewer software. Comparative analyses were employed to assess contributions between different countries, institutes, and researchers. With 21.26 citations per paper, 1206 papers cited 25,517 times were included. Mainland China contributed the most with 558 papers, with the most citations (6858 times) and the highest H-index (43). South Korea ranked first for number of papers per million people and per trillion gross domestic product (GDP). Keywords were stratified into two clusters by VOSviewer software: cluster 1, "treatments and effects"; and cluster 2, "characteristics". The average appearing years (AAY) of keywords in cluster 1 was more recent than that in cluster 2. For promising hotspots, "TNF-a" showed the latest AAY at 2014.09, followed by "migration", "angiogenesis", and "apoptosis". We conclude that the number of publications has been continuously growing dramatically since 2002 and that mainland China and South Korea are the most productive regions. The focus gradually shifts from "characteristics" to "treatments and effects". Attention should be drawn to the latest hotspots, such as "TNF-α", "migration", "angiogenesis", and "apoptosis". Furthermore, funding agencies might increase investments in exploring the therapeutic potential of UC-MSCs. [ABSTRACT FROM AUTHOR]

The article presents abstracts on transfusion medicine topics including human induced pluripotent stem cells for novel diagnosis, umbilical cord blood transfusion, and non-invasive haemoglobin testing for blood donor screening.

Umbilical cord blood (UCB) transplants (UCBTs) are becoming increasingly common in the treatment of a variety of hematologic and nonhematologic conditions. The T cells from UCB are naïve T cells, which have not yet been exposed to antigens and therefore do not contain T cells with specific immune functions against viruses. Cytomegalovirus (CMV) infections occur in more than 80% of patients after UCBT compared to other types of transplantation. Anti-CMV medications are currently restricted, with ganciclovir, foscarnet, and valganciclovir being the most common in China; however, with limited efficacy and considerable side effects, all these drugs are susceptible to viral resistance. In recent years, cytomegalovirus-specific T cells (CMVST) have advanced the treatment of viral infections in immunodeficient patients. CMVST usually uses the same donor as hematopoietic stem cell transplantation. CMVST should be administered to UCBT patients because of the absence of donors after UCBT. In China, there is no report on the use of CMVST to treat CMV infection after UCBT, and foreign reports are also limited. This paper reported a 20-year-old male patient with acute myeloid leukemia who developed cytomegalovirus retinitis (CMVR) after umbilical cord blood transplantation. After ineffective viral treatment, he was treated with a third-party donor CMVST and was successfully transformed into CMV nucleic acid negative. [ABSTRACT FROM AUTHOR]

Haematopoietic stem cell graft derived from cord blood is standard therapy for several haematological malignancies and other diseases. The study reports cases of public and private (family) cord blood biobanking services and the related hematopoietic stem cell transplantation ever performed in Hong Kong. The published original research papers and review articles from inception to Nov 2022 have been searched for on Pubmed, Microsoft Academic Search, and Google Scholar to identify reports on existing or terminated cord blood biobanking and transplantation service in Hong Kong. Moreover, all data publicly available on the offi - cial websites of the local cord blood banks and local mainstream media has been analysed. The public Hong Kong Red Cross Blood Transfusion Service delivers the highest quantity of haematopoietic stem cell transplants. Among the private sector, HealthBaby releases the most cord blood units for clinical use in diseases in both autologous and allogeneic administration, followed by Cordlife HK. Both public and private (family) cord blood biobanks have been and continue to contribute to the Hong Kong cord blood donor registry. However, the growth of the cord blood inventory is detrimental to donor-recipient matching for lifesaving therapy. [ABSTRACT FROM AUTHOR]

Transplantation from haploidentical donors is widely used, with progressive reduction of cord blood (CB) as alternative donor. The paper by Matsuda and colleagues, the largest analysing the outcome in non‐remission acute myeloid leukaemia (AML) transplanted with haploidentical donor or CB, suggests that CB is still a viable option when considering allogeneic transplantation for advanced AML. Commentary on: Matsuda et al. Comparison of transplant outcomes between haploidentical transplantation and single cord blood transplantation in non‐remission acute myeloid leukaemia: A nationwide retrospective study. Br J Haematol. 2023;201:106–113. [ABSTRACT FROM AUTHOR]

Transfusion-dependent thalassemia (TDT) is an inherited disorder characterized by absent or defective production of α- or β-hemoglobin chains. If untreated, the disease invariably culminates in death in early infancy due to cardiac failure or overwhelming infection. Although there is clear evidence of good health-related quality of life and return to normal life style, the choice to undergo hematopoietic stem cell transplantation (HSCT) remains a challenge because of the potential risk of transplant-related mortality (TRM) in TDT. Successful hematopoietic stem cell transplantation may cure the hematological manifestations of TDT, but introduces risks of TRM and morbidity. The low incidence of graft-versus-host disease (GVHD) provides the major rationale for pursuing unrelated cord blood transplantation (CBT). Considerable evidence suggests a lower rate of recurrence after CBT than after transplantation from adult donors. As the TRM, overall survival, and thalassemia-free survival for CBT improve, the utility of this stem cell source will expand to indications that have hitherto rarely used unrelated CBT. This paper summarizes the current progress in understanding the advances in unrelated CBT for thalassemia. Although as yet only in a limited number of patients, the results of unrelated CBT for thalassemia are encouraging. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment for severe aplastic anemia (SAA). It is known that SAA can evolve into malignant clonal diseases, such as acute myeloblastic leukemia (AML) or myelodysplastic syndrome. However, the transformation of SAA into AML after allo-HSCT is a rare phenomenon. Here, we report a case of SAA transformed into AML after patient received human leucocyte antigen (HLA)-matched sibling peripheral blood stem cell transplantation. Case Report: A 51-year-old female patient presented with petechiae and fatigue and received a diagnosis of idiopathic SAA. The immunosuppressive therapy combined with umbilical cord blood transplantation failed for this patient. Then, she received HLA-matched sibling allogeneic peripheral blood stem cell transplantation (allo-PBSCT). However, 445 days after allo-PBSCT, the patient had a diagnosis of AML by bone marrow puncture. Donor-recipient chi-merism monitoring and cytogenetic analysis confirmed that the leukemia was donor cell origin. Notably, a new HOXA11 mutation was detected in the peripheral blood of the patient after transplantation by whole-exome sequencing, which was the same gene mutation detected in the donor. The patient received 1 cycle of induction chemotherapy with azacytidine and achieved complete remission. However, the leukemia relapsed after 2 cycles of consolidation chemotherapy. Unfortunately, the patient died of leukemia progression 575 days after allo-HSCT. Conclusions: The mechanism of how normal donor hematopoietic cells transform to leukemia in the host remains unclear. Donor cell leukemia provides a unique opportunity to examine genetic variations in donors and hosts with regards to the progression to malignancy. [ABSTRACT FROM AUTHOR]

A recent study compared the outcomes of unrelated donor hematopoietic stem cell transplantation (URD-HSCT) and immunosuppressive therapy plus eltrombopag (IST + EPAG) as first-line treatments for adults with severe aplastic anemia (SAA). The study found that URD-HSCT had improved survival outcomes compared to IST + EPAG, but there was no significant difference in hematologic response or health-related quality of life between the two treatments. The study suggests that URD-HSCT could be considered as a first-line option for adult SAA patients without a matched sibling donor. Another study focused on the outcomes of URD-HSCT in patients with non-severe aplastic anemia. The results showed successful engraftment and low rates of graft failure, acute graft-versus-host disease (aGVHD), and chronic graft-versus-host disease (cGVHD). The incidence of aGVHD was higher in patients who received a mismatched unrelated donor compared to those who received a matched unrelated donor. Overall, URD-HSCT appears to be a favorable treatment option for adult SAA patients without a matched sibling donor, but further research is needed. [Extracted from the article]

Background: Although the use of cord blood transplantation (CBT) is becoming more frequent in acute leukemia, considering the relationship between the low stem cell dose and graft failure, whether use of CBT for adolescents and young adults (AYAs) is appropriate remains uncertain. Methods: A retrospective registry-based analysis of clinical outcomes and immune reconstitution was conducted for 105 AYAs and 187 children with acute leukemia who underwent single-unit CBT using myeloablative conditioning (MAC) without antithymocyte globulin (ATG). Results: Outcomes were similar between AYAs and children, except for nonrelapse mortality (NRM) and recovery rates of neutrophils and platelets. The 30-day cumulative incidence of neutrophil engraftment was similar between AYAs and children, but children had faster rates of neutrophil and platelet recovery than AYAs. The median time to neutrophil engraftment was earlier in children than in AYAs (AYAs, 19 days, 95% confidence interval [CI] 17.3–21.7; children, 16 days, 95% CI 13.1–19.5, p = 0.00003). The incidence of platelet recovery on day 120 was higher in children than in AYAs (AYAs, 80%, 95% CI 71–81%; children, 88%, 95% CI 82–92%, p = 0.037). CD34+ cell dose was the only independent factor influencing both neutrophil and platelet recovery. The cumulative incidence of NRM at 2 years was higher among AYAs than among children (AYAs, 27.5%, 95% CI 20–37%; children, 15%, 95% CI 10–21%, p = 0.008). Conditioning regimen was an independent factor influencing NRM. With respect to immune reconstitution, natural killer cell counts quickly recovered to normal levels 1-month post-CBT in both children and AYAs. CD8+ T-cell counts were higher in children than in AYAs at 1 and 3 months post-CBT. CD4+ T-cell counts were similar in both children and AYAs after CBT. Conclusion: AYAs with acute leukemia have outcomes of single-unit CBT using MAC without ATG that are as good as those of children. Thus, single-unit CBT using modified MAC without ATG is an acceptable choice for both AYAs and children who do not have a suitable donor. [ABSTRACT FROM AUTHOR]

The umbilical cord blood (UCB) donated in public UCB banks is a source of hematopoietic stem cells (HSC) alternative to bone marrow for allogeneic HSC transplantation (HSCT). However, the high rejection rate of the donated units due to the strict acceptance criteria and the wide application of the haploidentical HSCT have resulted in significant limitation of the use of UCB and difficulties in the economic sustainability of the public UCB banks. There is an ongoing effort within the UCB community to optimize the use of UCB in the field of HSCT and a parallel interest in exploring the use of UCB for applications beyond HSCT i.e., in the fields of cell therapy, regenerative medicine and specialized transfusion medicine. In this report, we describe the mode of operation of the three public UCB banks in Greece as an example of an orchestrated effort to develop a viable UCB banking system by (a) prioritizing the enrichment of the national inventory by high-quality UCB units from populations with rare human leukocyte antigens (HLA), and (b) deploying novel sustainable applications of UCB beyond HSCT, through national and international collaborations. The Greek paradigm of the public UCB network may become an example for countries, particularly with high HLA heterogeneity, with public UCB banks facing sustainability difficulties and adds value to the international efforts aiming to sustainably expand the public UCB banking system. [ABSTRACT FROM AUTHOR]

Background: Successful hematopoietic stem cell transplantation (HSCT) could cure the hematological manifestations of transfusion-dependent thalassemia (TDT) but introduces risks of morbidity and mortality. Umbilical cord blood transplantation (UCBT) is considered as an acceptable strategy, by providing a condensed graft versus host disease (GvHD). This paper compares the outcomes of UCBT with HSCT from peripheral blood and bone marrow in TDT patients. Methods: Between 1998 and 2014, 10 patients with TDT underwent UCBT, which were matched with 20 patients undergone BMSCT and 20 patients undergone PBSCT, by using propensity score matching (PSM) for age, gender and thalassemia class. All patients received the same myeloablative conditioning regimen and were transplanted from a fully HLA matched sibling donor. Results: The median follow-up time after HSCT was 5.7 years. Rejection incidence was 70.0% (95% CI = 28.1%-90.4%) after UCBT, 25.6% (95% CI = 8.9%-46.4%) after BMSCT, and no rejection occurred in the PBSCT group. Acute GVHD incidence was 20.0% (95% CI = 2.6%-49.0%), 35.0% (95% CI = 15.1%-55.8%), and 40.0% (95% CI = 18.6%-60.6%) in patients undergone UCBT, BMSCT and PBSCT, respectively (P=0.62). The incidence of chronic GVHD was 7.2% (95% CI = 0.3%-28.7%), and 35.2% (95% CI = 13.7%-57.8%) in patients undergone BMSCT and PBSCT, respectively (P=0.026) and none of the patients in the UCBT group experienced chronic GvHD. Conclusions: Although the overall survival is not significantly influenced by the graft source, due to the high incidence of rejection after UCBT, the probability of thalassemia free survival is very low in these patients. [ABSTRACT FROM AUTHOR]

Blood stem cell transplants can be life-saving for some patients, but the chances of finding a matching donor are small unless a large number of potential donors are evaluated. Many nations maintain large registries of potential donors who have offered to donate stem cells if they are the best available match for a patient needing a transplant. An alternative source of stem cells, umbilical cord blood, is stored in banks. Everyone faces a small probability of needing a transplant which will increase their likelihood of survival. The registries and cord blood banks are thus an interesting example of a pure public good with widely dispersed benefits. This paper explores the gains in survival probability that arise from increased registry and bank sizes and uses value of statistical life methods to estimate benefits and compare them to costs. Our results suggest that for the United States and for the world as a whole, the sum of marginal benefits of an increase in either the adult registry or the cord blood bank exceeds marginal costs. However, marginal benefit-cost ratios for the adult registry are much greater than those for the cord blood banks, which suggests that to the extent that these two sources of life saving compete for public funds it may be preferable to prioritize expansion of the adult registry over cord blood banks. [ABSTRACT FROM AUTHOR]

Objective: Hematopoietic stem cell transplantation has been successfully used to treat the pediatric population with malignant and non-malignant hematological diseases. This paper reports the results up to 180 days after the procedure of all unrelated hematopoietic stem cell transplantations in pediatric patients that were performed in one institution. Methods: A retrospective review was performed of all under 18-year-old patients who received unrelated transplantations between 1995 and 2009. Data were analyzed using the log-rank test, Cox stepwise model, Kaplan-Meier method, Fine and Gray model and Fisher's exact test. Results: This study included 118 patients (46.8%) who received bone marrow and 134 (53.2%) who received umbilical cord blood transplants. Engraftment occurred in 89.47% of the patients that received bone marrow and 65.83% of those that received umbilical cord blood (p-value < 0.001). Both neutrophil and platelet engraftments were faster in the bone marrow group. Acute graft-versus-host disease occurred in 48.6% of the patients without statistically significant differences between the two groups (p-value = 0.653). Chronic graft-versus-host disease occurred in 9.2% of the patients with a higher incidence in the bone marrow group (p-value = 0.007). Relapse occurred in 24% of the 96 patients with malignant disease with 2- year cumulative incidences of 45% in the bone marrow group and 25% in the umbilical cord blood group (p-value = 0.117). Five-year overall survival was 47%, with an average survival time of 1207 days, and no significant differences between the groups (p-value = 0.4666). Conclusion: Despite delayed engraftment in the umbilical cord blood group, graft-versus-host disease, relapse and survival were similar in both groups. [ABSTRACT FROM AUTHOR]

Stenotrophomonas maltophilia (S. maltophilia) is an aerobic nonfermenting Gram-negative bacillus widely distributed in the environment that has inherent multidrug resistance to beta-lactam and carbapenem antibiotics. S. maltophilia infection (SMI) is known as an important fatal complication following allogeneic hematopoietic stem cell transplantation (HSCT), but its clinical characteristics have not been well clarified. A retrospective study to identify the incidence, risk factors, and outcomes of SMI after allogeneic HSCT was performed using the database of the Japanese nationwide registry, including 29,052 patients who received allogeneic HSCT in Japan between January 2007 and December 2016. A total of 665 patients developed SMI (sepsis/septic shock, 432; pneumonia, 171; other, 62). The cumulative incidence of SMI at 100 days after HSCT was 2.2%. Among risk factors identified for SMI (age ≥ 50 years, male, performance status 2–4, cord blood transplantation [CBT], myeloablative conditioning, Hematopoietic Cell Transplant-Comorbidity Index [HCT-CI] score 1–2, HCT-CI score ≥ 3, and active infectious disease at HSCT), CBT was the strongest risk factor (hazard ratio, 2.89; 95%CI, 1.94–4.32; p < 0.001). The survival rate at day 30 after SMI was 45.7%, and SMI before neutrophil engraftment was significantly associated with poor survival (survival rate 30 days after SMI, 40.1% and 53.8% in patients with SMI before and after engraftment, respectively; p = 0.002). SMI is rare after allogeneic HSCT, but its prognosis is extremely poor. CBT was a strong risk factor for SMI, and its development prior to neutrophil engraftment was associated with poor survival. [ABSTRACT FROM AUTHOR]

Matsuda et al.[1] recently described the outcomes of patients with "non-remission" acute myeloid leukaemia (AML) after haematopoietic stem cell transplantation (HSCT) using readily available alternative donors: cord blood (CB) and haplo-identical (Haplo) donors. This very well written manuscript, however, did not emphasize an important finding: that patients with active disease who received a myeloablative CB transplant had an approximately 1.5-fold higher probability of survival compared to those with haplo-donors. Intensified conditioning regimens improved disease-free survival and engraftment after unrelated single-unit cord blood transplantation but not after matched sibling or matched unrelated donor allogeneic hematopoietic cell transplantation. [Extracted from the article]

A 69-year-old woman was diagnosed with acute myeloid leukemia (AML) with an FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation. Complete remission (CR) was achieved after induction therapy, but AML resulted in a hematological relapse two months after the consolidation chemotherapy. Relapse was accompanied by multiple skin lesions that demonstrated leukemic cell infiltration as well as a drooping right eyelid with extroversion of the eye due to right oculomotor palsy. Gilteritinib was started as salvage therapy, and bone marrow blasts decreased to 0.8% after one month. Two months later, the eye symptoms improved, and the patient underwent cord blood transplantation (CBT). The skin lesions disappeared after the conditioning regimen, and the patient achieved CR status with complete donor chimerism at day 28. Gilteritinib was restarted as posttransplant maintenance therapy on day 53 of CBT. No adverse events other than mild hepatotoxicity were observed, and the patient was alive and in CR status, while continuing gilteritinib at one year and seven months after CBT. Bridging and posttransplant maintenance therapy with gilteritinib may be a promising therapeutic option for relapsed AML with the FLT3-ITD mutation in elderly patients. [ABSTRACT FROM AUTHOR]

The biosafety of gene therapy remains a crucial issue for both the direct and cell-mediated delivery of recombinant cDNA encoding biologically active molecules for the pathogenetic correction of congenital or acquired disorders. The diversity of vector systems and cell carriers for the delivery of therapeutic genes revealed the difficulty of developing and implementing a safe and effective drug containing artificial genetic material for the treatment of human diseases in practical medicine. Therefore, in this study we assessed changes in the transcriptome and secretome of umbilical cord blood mononuclear cells (UCB-MCs) genetically modified using adenoviral vector (Ad5) carrying cDNA encoding human vascular endothelial growth factor (VEGF165) or reporter green fluorescent protein (GFP). A preliminary analysis of UCB-MCs transduced with Ad5-VEGF165 and Ad5-GFP with MOI of 10 showed efficient transgene expression in gene-modified UCB-MCs at mRNA and protein levels. The whole transcriptome sequencing of native UCB-MCs, UCB-MC+Ad5-VEGF165, and UCB-MC+Ad5-GFP demonstrated individual sample variability rather than the effect of Ad5 or the expression of recombinant vegf165 on UCB-MC transcriptomes. A multiplex secretome analysis indicated that neither the transduction of UCB-MCs with Ad5-GFP nor with Ad5-VEGF165 affects the secretion of the studied cytokines, chemokines, and growth factors by gene-modified cells. Here, we show that UCB-MCs transduced with Ad5 carrying cDNA encoding human VEGF165 efficiently express transgenes and preserve transcriptome and secretome patterns. This data demonstrates the biosafety of using UCB-MCs as cell carriers of therapeutic genes. [ABSTRACT FROM AUTHOR]

Objective: To investigate similarities and differences in immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with Wiskott-Aldrich syndrome (WAS) and chronic granulomatous disease (CGD). Method: We retrospectively analyzed the lymphocyte subpopulations and the serum level of various immune-related protein or peptide on Days 15, 30, 100, 180 and 360 post-transplantation in 70 children with WAS and 48 children with CGD who underwent allo-HSCT at the Transplantation Center of the Department of Hematology-Oncology, Children's Hospital of Chongqing Medical University from January 2007 to December 2020, and we analyzed the differences in the immune reconstitution process between the two groups. Results: ① The WAS group had higher lymphocyte subpopulation counts than the CGD group. ② Among children aged 1-3 years who underwent transplantation, the WAS group had higher lymphocyte subpopulation counts than the CGD group. ③ Further comparisons were performed between children with non-umbilical cord blood transplantation (non-UCBT) and children with umbilical cord blood transplantation (UCBT) in the WAS group. On Day 15 and 30 post-transplantation, the non-UCBT group had higher B-cell counts than the UCBT group. On the remaining time points post-transplantation, the UCBT group had higher lymphocyte subpopulation counts than the non-UCBT group. ④ Comparisons were performed between children with non-UCBT in the WAS group and in the CGD group, the lymphocyte subpopulation counts were higher in the WAS group compared to the CGD group. ⑤ On Day 100 posttransplantation, the CGD group had higher C3 levels than the WAS group. On Day 360 post-transplantation, the CGD group had higher IgA and C4 levels than the WAS group. Conclusion: ① The rate of immunity recovery was faster in children within the WAS group compared to those children within the CGD group, which may be attributed to the difference of percentage undergoing UCBT and primary diseases. ② In the WAS group, the non-UCBT group had higher B-cell counts than the UCBT group at Day 15 and 30 post-transplantation, however, the UCBT group had higher B-cell counts than the non-UCBT group at Day 100 and 180 post-transplantation, suggesting that cord blood has strong B-cell reconstitution potentiality after transplantation. [ABSTRACT FROM AUTHOR]

Telomere length in CD4+ and CD8+ T cells among long-term survivors of adults after single cord blood transplantation Relative telomere length in CD4+ T cells and CD8+ T cells according to the NIH grade of cGVHD (F). Correlation between time since CBT to TL assessment and relative telomere length in CD4+ T cells (H) or CD8+ T cells (I). [Extracted from the article]

Candida colonization is associated with severe acute GVHD in adult patients undergoing single-unit cord blood transplantation Our study showed that candidemia occurred in two previous I Candida i -colonized patients, indicating that I Candida i colonization is not useful predictor for the development of candidemia after CBT. This is consistent with previous studies.[[2]] However, this result should be interpreted with caution because antifungal therapy was changed based on the results of an antifungal susceptibility test of the isolated I Candida i during neutropenic episode. [Extracted from the article]

Given that all six patients developed thyrotoxicosis with no apparent antecedent infection, immune-mediated reactions might be associated with thyrotoxicosis after CBT. A retrospective study by EUROCORD showed that autoimmune diseases occurred after CBT in approximately 5% of patients, and the most common autoimmune disease was cytopenia followed by autoimmune diseases of the thyroid [[10]]. Dear Editor, Thyroid dysfunction is a common endocrine complication after allogeneic hematopoietic cell transplantation (HCT). [Extracted from the article]

Background: Mesenchymal stem cells (MSCs) have been used for ex vivo expansion of umbilical cord blood (UCB) hematopoietic stem cells (HSCs) to maintain their primitive characters and long-term reconstitution abilities during transplantation. Therapeutic effects of MSCs mainly rely on paracrine mechanisms, including secretion of exosomes (Exos). The objective of this study was to examine the effect of cord blood plasma (CBP)-derived Exos (CBP Exos) and Placental MSCs-derived Exos (MSCs Exos) on the expansion of UCB HSCs to increase their numbers and keep their primitive characteristics. Methods: CD34+ cells were isolated from UCB, cultured for 10 days, and the expanded HSCs were sub-cultured in semisolid methylcellulose media for primitive colony forming units (CFUs) assay. MSCs were cultured from placental chorionic plates. Results: CBP Exos and MSCs Exos compared with the control group significantly increased the number of total nucleated cells (TNCs), invitro expansion of CD34+ cells, primitive subpopulations of CD34+38+ and CD34+38−Lin− cells (p < 0.001). The expanded cells showed a significantly higher number of total CFUs in the Exos groups (p < 0.01). Conclusion: CBP- and placental-derived exosomes are associated with significant ex vivo expansion of UCB HSCs, while maintaining their primitive characters and may eliminate the need for transplantation of an additional unit of UCB. [ABSTRACT FROM AUTHOR]

Background and Objectives: In Japan, cord blood is used for more than half of all unrelated stem cell transplantations. The public cord blood banks (CBBs) have been collecting information on cord blood transplantation‐related adverse events from physicians on a voluntary basis, without common definitions of the adverse reactions. The aims of this study were to compare two classification systems to improve the reporting system and to clarify the actual risk from cord blood infusion, which can then provide the impetus to take appropriate measures to reduce adverse events. Materials and Methods: We classified the reports according to existing criteria; one is the Proposed Standard Definitions for Surveillance of Non‐Infectious Adverse Transfusion Reactions by the International Society of Blood Transfusion (ISBT) Working Party on Haemovigilance, and the other is the Common Terminology Criteria for Adverse Events (CTCAE). There were 140 cases with adverse events reported from April 2014 through March 2019. Results: Twelve cases, such as donor‐derived leukaemia/myelodysplastic syndromes (MDS) and chromosomal aberrations reported after engraftment, were excluded from this analysis. Of the 128 cases with adverse events at cord blood infusion, the CTCAE and ISBT criteria could not classify 6 cases and 68 cases, respectively. Classifying by the CTCAE, the most common side effect was hypertension in 35 cases, followed by anaphylaxis, allergic reactions, nausea, urticaria, etc. Serious adverse events (grades 4 and 5) were mainly anaphylaxis, with a frequency of 0.23%. Conclusion: It is necessary not only to provide information on adverse events but also to standardize the reporting of adverse events to support measures to reduce them. [ABSTRACT FROM AUTHOR]

Background: Haploidentical (haplo‐) donors and cord‐blood (CB) stem cells provide alternative transplant options in patients lacking an HLA‐matched donor. In case of relapse or graft failure after a first alternative allogeneic hematopoietic stem cell transplant (HSCT), a second alternative HSCT (HSCT2) is rarely considered due to a high risk of toxicity. Methods: A retrospective French multicentre study was performed, including patients with hematologic malignancies who underwent two consecutive HSCT from alternative donors. All data were exported from the national ProMISE database between 2000 and 2016. Results: Forty‐three patients (61.4%) received a CB‐HSCT2 and 27 (38.6%) a haplo‐HSCT2. Indications for HSCT were graft failure (51.4%) or disease progression (48.6%). Two‐years probabilities of overall survival, progression‐free survival and toxicity‐related mortality were 18.5%, 17.8% and 55.8%, respectively. In multivariate analysis, complete remission status at HSCT2 and year of HSCT2 ≥ 2012 were significantly associated with a better outcome (with respectively hazard ratio [HR] = 0.42, p =.002 and HR = 0.5, p =.051). Conclusions: Neither the indication of HSCT2 nor the source of stem cell was more advantageous towards overall patient survival. A salvage haploidentical or cord‐blood stem cell transplantation is a high‐risk procedure, that may be considered for patients achieving a complete remission before receiving the second HSCT. [ABSTRACT FROM AUTHOR]

In overall 41 patients with APL, we compared those who had BM and CNS relapse ( I N i = 6) with those who had a sole BM relapse ( I N i = 6) and those without BM nor CNS relapse ( I N i = 28) (Supplemental Table 1). Even in the era of treatment of molecularly targeted therapies, the appropriate management of acute promyelocytic leukemia (APL) relapse in the central nervous system (CNS) has not been established. Further prognostic investigation of patients with CNS involvement revealed that while all three dead patients had cytological CNS relapse, three patients with only molecular CNS relapse had survived. Dead patients were 10 of 41 (24%) overall patients, three of six (50%) patients with BM and CNS relapse, and one of six (17%) patients with a sole BM relapse. [Extracted from the article]

Two individuals (patients 7 and 8) received immune checkpoint inhibition (ICI) prior to BMT; patient 7 received anti-CTLA-4 and anti-PD-1 combination therapy, and patient 8 received anti-PD-L1 and interferon combination therapy. From 2003 to 2020, eight patients received partially mismatched donor BMT for relapsed/refractory MF/SS. Seven patients received grafts from HLA-haploidentical related donors. Primary cutaneous T-cell lymphomas (CTCLs), a heterogeneous group of extranodal non-Hodgkin lymphomas involving the skin, are dominated by two main subtypes: mycosis fungoides (MF) and Sézary syndrome (SS) [[1]]. An eighth patient (patient 5) experienced graft failure after double unrelated donor umbilical cord blood transplantation and within 6 months underwent partially mismatched unrelated donor BMT. [Extracted from the article]

Donor cell-derived leukemia (DCL) is a special type of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients with DCL generally have a poor prognosis due to resistance to conventional chemotherapy. Here, we report a case of donor cell-derived acute lymphoblastic leukemia after umbilical cord blood transplantation. The patient didn’t respond to induction chemotherapy. She then received antiCD19 CAR-T cell therapy and achieved MRD-negative complete remission (CR). However, MRD levels rose from negative to 0.05% at 5 months after CART cell therapy. Higher MRD levels were significantly associated with an increased risk of leukemia recurrence. Afterward, preemptive interferon-a treatment was administrated to prevent disease recurrence. To date, the patient has maintained MRD-negative CR for 41 months. Our results suggested that anti-CD19 CAR-T cells followed by interferon-a therapy are effective in treating donor cell-derived acute lymphoblastic leukemia. This report provides a novel strategy for the treatment of DCL. [ABSTRACT FROM AUTHOR]

Progressive multifocal leukoencephalopathy (PML) is a rare neurological disease caused by the reactivation of latent John Cunningham polyomavirus. Hematological disorders associated with immunomodulatory monoclonal antibodies and hematopoietic stem cell transplantation (HSCT) are risk factors for PML. Blinatumomab is a novel antileukemic immunomodulatory agent and more effective for relapsed and refractory acute lymphoblastic leukemia (ALL) than conventional chemotherapy. But, blinatumomab suppresses humoral immunity due to long-lasting B-cell depletion during and after the treatment. The development of PML involves cellular immunity and impairment of humoral immunity. Although few cases of blinatumomab-related PML have been reported, the use of blinatumomab after allogeneic HSCT may increase the risk of developing PML. The current case report presents a patient of Philadelphia chromosome-positive ALL wherein PML developed after cord blood stem cell transplantation and administrating blinatumomab. [ABSTRACT FROM AUTHOR]

Venetoclax (VEN) is an oral B-cell lymphoma-2 (BCL-2) inhibitor that has been widely used to treat various hematological disorders. Recent studies have demonstrated that VEN in combination with fludarabine-enhanced high-dose cytarabine (FLA) is effective for treating relapsed or refractory acute myeloid leukemia (AML). In the combination therapy, salvage chemotherapy and VEN are basically concurrently administrated; however, further optimization may enable the treatment to apply to larger numbers of patients with various clinical backgrounds. Here, we describe a case of refractory AML treated with a sequential combination of the intensive chemotherapy (fludarabine, cytarabine, and mitoxantrone; FLAM) and VEN/AZA to bridge to an unrelated cord blood transplantation (uCBT). By continuously adding VEN/AZA after FLAM, the patient achieved morphologic leukemia free state with only minor toxicities. Blood cell counts did not recover until the time of transplantation because of the deep myelosuppression caused by the treatment sequence, but the infection risk was safely managed during this period. After engraftment, maintenance therapy with VEN/AZA was performed, and the patient has survived without disease recurrence for over 9 months after transplantation. Our case suggests that bridging therapy with VEN and AZA from the time of the last chemotherapy to allogeneic transplantation may provide an effective and tolerable treatment strategy for refractory AML. Further studies of larger numbers of cases are needed to validate the effectiveness of this treatment. [ABSTRACT FROM AUTHOR]

The clinical influence of preformed nonspecific anti-HLA antibodies on single-unit umbilical cord blood transplantation in patients with haematological malignancies For over 30 years, umbilical cord blood transplantation (UCBT) has been an option available to patients who require allogeneic haematopoietic stem cell transplantation (allo-HSCT) but for whom a human leukocyte antigen (HLA)-matched sibling or unrelated donor is unavailable.1 Anti-HLA antibodies (AHAs) are antibodies that target class I and II HLA antigens and are mostly produced in response to foreign antigens during pregnancy, blood transfusion, or solid organ transplantation. Among the 392 patients, seventy-three patients (18.6%) were positive for AHAs and were considered the AHA-positive group, and the remaining 319 patients were considered the AHA-negative group. [Extracted from the article]

The frequencies and diversities of human leukocyte antigen (HLA) alleles and haplotypes are representative of ethnicities. Matching HLA alleles is essential for many clinical applications, including blood transfusion, stem cell transplantation, and tissue/organ transplantation. To date, the information about the frequencies and distributions of HLA alleles and haplotypes among the Kinh Vietnamese population is limited because of the small sample size. In this study, more than 3,750 cord blood units from individuals belonging to the Kinh Vietnamese population were genotyped using PCR sequence-specific oligonucleotide (PCR-SSO) for HLA testing. The results of the study demonstrated that the most frequently occurring HLA-A, -B, -C, and -DRB1 alleles were A*11:01 (25%), A*24:02 (12.3%), A*02:01 (11.2); A*03:03 (8.95%), A*02:03 (7.81%), A*29:01 (7.03%); B*15:02 (15.1%), B*46:01 (10.7%), B*58:01 (7.65%), B*38:02 (7.29%); C*08:01 (17.2), C*07:02 (16.2%), C*01:02 (15.2), C*03:02 (8.3%), C*15:05 (6.13); DRB1*12:02 (31.0%), DRB1*09:01 (10.47%), DRB1*15:02 (7.54%); DRB1*07:01 (6.68%), DRB1*10:01 (6.63%), respectively, with the highest allele diversity level observed in locus B (93 alleles). The most frequent haplotypes of two-locus combinations of HLA-A–B, HLA-A–C, HLA-A–DRB1, HLA-B–C, HLA-B–DRB1, and HLA-C–DRB1 haplotypes were A*11:01–B*15:02 (7.63%), A*11:01–C*08:01 (7.98%), A*11:01–DRB1*12:02 (10.56%), B*15:02–C*08:01 (14.0%), B*15:02–DRB1*12:02 (10.47%), and C*08:01–DRB1*12:02 (11.38%), respectively. In addition, the most frequent haplotypes of three- and four-locus sets of HLA-A–B–C, HLA-A–B–DRB1, HLA-A–C–DRB1, HLA-B–C–DRB1, and HLA-A–B–C–DRB1 were A*11:01–B*15:02–C*08:01 (7.57%), A*11:01–B*15:02–DRB1*12:02 (5.39%), A*11:01–C*08:01–DRB1*12:02 (5.54%), B*15:02–C*08:01–DRB1*12:02 (10.21%), and A*11:01–B*15:02–C*08:01–DRB1*12:02 (5.45%), respectively. This study provides critical information on the frequencies and distributions of HLA alleles and haplotypes in the Kinh Vietnamese population, accounting for more than 85% of Vietnamese citizens. It paves the way to establish an umbilical cord blood bank for cord blood transplantation programs in Vietnam. [ABSTRACT FROM AUTHOR]

Umbilical cord blood unit (CBU) "quantity" continues to grow internationally, while cord blood transplantation (CBT) "quality" remains poorly defined and subject to uncertainty. CBT "quality" is affected by both the product (i.e. CBUs) and CBT processes, with "best practice" varying across countries. To improve overall CBT "quality", we need to better understand the uncertainty associated with CBUs and CBT processes and how staff manage it. In this qualitative study, we conducted in-depth semi-structured interviews with individuals working in CBT in UK and Japan. We found that understanding of CBT quality by the cord blood community is underpinned by the quality of the CBU, the expertise and collaboration of scientific and clinical stakeholders, trust in collection and testing processes and international accreditation. Importantly, we found that local and individual experience is used to manage uncertainty within CBT, and we propose that selection guidelines should acknowledge the extent of uncertainty in decision-making. [ABSTRACT FROM AUTHOR]

Comparative studies between total body irradiation (TBI)-based and busulfan-based myeloablative conditioning (MAC) regimens for cord blood transplantation (CBT) have been limited. We retrospectively analyzed the results of single-unit CBT in 333 adult patients who received either TBI-based (n = 258) or busulfan-based (n = 75) MAC regimens at our institute. After adjusting for significant variables in the univariate analysis, there were no significant differences in neutrophil recovery (hazard ratio (HR), 0.88; p =.460), grade III–IV acute graft-versus-host disease (GVHD) (HR: 1.40, p =.410), extensive chronic GVHD (HR: 0.73, p =.380), relapse (HR: 0.61, p =.270), non-relapse mortality (HR: 1.38, p =.420), overall survival (HR: 1.18, p =.637), or event-free survival (HR: 1.08, p =.773), although platelet recovery was lower with marginal significance for the busulfan-based regimen (HR: 0.67, p =.068). In subgroup analysis, TBI-based regimens were superior to busulfan-based regimens in terms of survival for acute lymphoblastic leukemia, but not for myeloid malignancies. Further investigation is warranted even for CBT. [ABSTRACT FROM AUTHOR]

Background: While chimeric antigen receptor (CAR)-T cell therapy is becoming widely used in hematological malignancies with remarkable remission rate, their high recurrence remains an obstacle to overcome. The role of consolidative transplantation following CAR-T cell-mediated remission remains controversial. We conducted a retrospective study to explore whether bridging to unrelated cord blood transplantation (UCBT) could improve the prognosis of patients entering remission after CAR-T therapy with different characteristics through subgroup analyses. Methods: We reviewed 53 patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) successfully infused with CD19 CAR-T cells and achieved complete remission (CR). In this study, 25 patients received consolidative UCBT (UCBT group) and 28 patients did not accept any intervention until relapse (non-UCBT group). Subgroup analysis on prognosis was then performed according to gender, age, number of previous relapses, tumor burden, presence of poor prognostic markers, and structure of CAR. Results: Compared with the non-UCBT group, patients who underwent consolidative UCBT had better median event-free survival (EFS; 12.3 months vs. 6.2 months; P = 0.035) and relapse-free survival (RFS; 22.3 months vs. 7.2 months; P = 0.046), while no significant difference was found in overall survival (OS; 30.8 months vs. 15.3 months; P = 0.118). Subsequent multivariate analysis revealed that bridging to UCBT was a protective factor for RFS (P = 0.048) but had no significant effect on EFS (P = 0.205) or OS (P = 0.541). In the subgroup analysis, UCBT has an added benefit in patients with specific characteristics. Patients who experienced ≥2 relapses or with sustained non-remission (NR) showed better RFS (P = 0.025) after UCBT. Better EFS was seen in patients with poor prognostic markers (P = 0.027). In the subgroup with pre-infusion minimal residual disease (MRD) ≥5% or with extramedullary disease (EMD), UCBT significantly prolonged EFS (P = 0.009), RFS (P = 0.017), and OS (P = 0.026). Patients with occurrence of acute graft-versus-host disease (aGVHD) appeared to have a longer duration of remission (P = 0.007). Conclusion: Consolidative UCBT can, to some extent, improve clinical outcomes of patients with R/R B-ALL entering remission following CD19 CAR-T therapy, especially in patients with more recurrences before treatment, patients with poor prognostic markers, and patients with a higher tumor burden. The occurrence of aGVHD after UCBT was associated with better RFS. [ABSTRACT FROM AUTHOR]

A review of the article "Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells" by Stefan Rentas in the journal "Nature" is presented.

The article presents a case study of a 10-year-old girl with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH). Topics discussed include the role of cytokine profiling in disease monitoring, the challenges of assessing disease activity in HLH, and the potential utility of cytokine measurement, particularly interleukin-18, interferon-gamma, and chemokine ligand 9, in evaluating HLH activity.