Risk factors of CMV infection in patients after umbilical cord blood transplantation: a multicenter study in China

Objective： This retrospective study examined risk factors for cytomegalovirus （CMV） infection after umbilical cord blood transplantation （UCBT） and the impact of CMV infection on patient survival. Methods： In all 176 patients, plasma CMV DNA was negative prior to the transplantation, and examined twice a week for 100 d, and then once weekly for additional 300 d. Preemptive antiviral therapy （ganciclovir or foscarnet） was started in patients with 〉 1,000/mL copies of CMV DNA but no full-blown CMV disease, and was discontinued upon two consecutive negative reports of blood CMV DNA test. The survival and risk factors for CMV infection or disease were examined using logistic regression. Results： CMV infection developed in 71% （125/176） of the patients, with a median onset of 32 d. Four patients （2.3%） developed CMV disease. Neither the 5-year overall survival （OS） nor event-free survival （EFS） differed significantly in infected patients vs. those with no infection （59.4% vs. 64.8%, P=0.194; 53.4% vs. 59.1%, P=0.226）. A stepwise multivariate analysis indicated an association of CMV infection with age, high-dose glucocorticoids, the number of transplanted CD34^＋ cells, and the number of platelet transfusion, but not with gender, the conditioning regimen, and the day of neutrophil recovery and chronic graft-versus- host disease （cGVHD）. Conclusions： CMV infection is very common after UCBT, but does not seem to affect long-term survival with preemptive antiviral treatment.

Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease

Background:With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation(UCBT),the correlation between immune reconstitution(IR)after UCBT and graft-versus-host disease(GVHD)has been reported successively,but reports on double-negative T(DNT)cell reconstitution and its association with acute GVHD(aGVHD)after UCBT are lacking.Methods:A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology,the First Affiliated Hospital of USTC,between August 2018 and June 2021.IR differences were compared between the patients with and without aGVHD.Results:The absolute number of DNT cells in the healthy Chinese population was 109(70-157)/μL,accounting for 5.82(3.98-8.19)%of lymphocytes.DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation.Importantly,the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year(F=4.684,P=0.039 and F=5.583,P=0.026,respectively).In addition,the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased,and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD(HR=0.46,95%confidence interval[CI]:0.23-0.93;P=0.031).Conclusions:Compared to the number of DNT cells in Chinese healthy people,the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow.In addition,the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

Cord blood transplantation for the treatment of acute leukemia

Objective This review discussed the available data on treatment outcomes of cord blood transplantation （CBT） for acute leukemia. Data sources The data cited in this review were obtained from articles listed in Medline and Pubmed. Study selection We reviewed the articles of clinical results from various registries and institutions, as well as our experiences with CBT in children, adolescents and adults. Results This research has clearly shown that cord blood （CB） has several unique characteristics resulting in distinct advantage and disadvantages when compared to transplantation with unrelated donor bone marrow or peripheral blood stem cells. The field of CBT has advanced from investigating its safety and feasibility to addressing more specific issues such as accelerating engraftment, extending access, and examining outcomes in specific subgroups of patients. Many approaches have been investigated in the attempt to improve engraftment and survival. Variable factors have been identified, such as factors related to donor choice （human leukocyte antigen （HLA） compatibility, cell dose, and others） and transplantation （conditioning and graft-versus-host disease prophylaxis regimen）. Data support that CB should be considered a reasonable option in those that do not have HLA matched sibling donor and for those in whom the time to transplant is critical. Conclusions CB is a reasonable alternative to unrelated donor bone marrow or peripheral blood progenitor cells for transplantation. Recently developed strategies aimed at improving hematopoietic recovery and reducing early transplantation-related mortality could further improve treatment outcomes of CBT for patients with acute leukemia.

Comparative outcomes between cord blood transplantation and bone marrow or peripheral blood stem cell transplantation from unrelated donors in patients with hematologic malignancies： a single-institute analysis

Background Umbilical cord blood （UCB） has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients. Our aim was to assess the leukemia-free survival （LFS） and some primary results, such as hematologic recovery, risk of graft-versus-host disease （GVHD）, relapse, and long-term survival, after unrelated cord blood transplantation compared with the outcomes of transplantations from other unrelated graft source. Methods The clinical outcomes of 112 consecutive patients with acute leukemia who received umbilical cord blood （UCBT） as a primary unrelated stem cell source （n=38）, bone marrow （UBMT n=28, transplanted before January 2003）, or peripheral blood stem cells （UPBSCT n=46, transplanted after January 2003） between July 2000 and July 2008 were analyzed. Results Except that the patients were much younger in the UCBT group （median age, 10.5 years in UCBT, 30 years in UPBSCT, and 20 years in UBMT）, other pre-transplant parameters, such as gender, diagnosis, and the phase of disease, were comparable. All patients received myeloablative regimens, primarily including BUCY; however, there was less anti- thymocyte globulin （ATG） used for the UBMT patients （2/38 in UCBT, 0/46 in UPBSCT, and 8/28 in UBMT did not use ATG, P=0.000）. Significant delays in engraftment occurred after UCBT for both neutrophil cells and platelets. The cumulative allo-engraftment rates were also significantly lower （87.8% vs. 97.8% vs. 100% for WBC, P=0.000; 73.0% vs. 97.5% vs. 89.5% for PLT, P=0.000） for UCBT. The incidence of Grade 2-4 and 3-4 acute graft versus host disease （aGVHD） was much higher in the UBMT group but did not differ among the other groups （51% and 13.2%, 40.2% and 10.5%, and 77.4% and 41.2%, respectively, for UCBT, UPBSCT, and UBMT, P=0.000）. The occurrence of extensive chronic GVHD （cGVHD） was significantly decreased for recipients of UCBT （4%） compared with that of UPBSCT （39.1%） and UBMT （49.1%, P=0.000）, although the rates of whole cGVHD were not significantly different （30.3%, 63.1%, and 60.1% for UCBT, UPBSCT, and UBMT, respectively）. The patients had a similar rate of CMV infection （21/38, 28/46, and 22/28 for UCBT, UPBSCT, and UBMT, respectively）, while the HC occurrence was lower after UCBT （7/38, 16/46, and 14/28 for UCBT, UPBSCT, and UBMT, respectively）. As of August 2012, there was no apparent difference in 5-year overall survival （OS）, LFS, or the relapse rate for each graft source （52.5%, 52.6%, and 20.8% in UCBT; 48.7%, 46.4%, and 27.9% in UPBSCT; and 46.4%, 42.9%, and 16.0% in UBMT）. Conclusion These data support the use of UCB donors as an alternative allogeneic donor.

Vein transplantation using human umbilical cord blood stem cells in the treatment of stroke sequela

BACKGROUND: Transplanted mononuclear cell (MNC) of umbilical blood can survive in central nervous system (CNS) of host through blood brain barrier, differentiate into nerve cells, migrate to damaged site and integrate morphological structure and function with nerve cells of host so as to improve deficiencies of sensatory function, motor function and cognitive function and influence on stroke sequela. OBJECTIVE: To observe the vein transplantation of human umbilical cord blood stem cells (HUCBSC) for improving neurological function, limb function and activity of daily living of patients with stroke and evaluate the reliability. DESIGN: Self-controlled study. SETTING: Department of Neurosurgery, the Second People's Hospital of Zhengzhou City; Red-crossed Blood Center of Henan Province; Department of Neurosurgery, the Fist Affiliated Hospital of Zhengzhou University. PARTICIPANTS: A total of 10 patients with stroke sequela were selected from Department of Cerebral Surgery, the Second People's Hospital of Zhengzhou City from April to December 2005. There were 9 males and 1 female aged from 35 to 75 years with the mean age of 56 years. All of them were diagnosed with CT and MRI examination and coincidence with diagnostic criteria of stroke established by the Fourth National Academic Meeting for Cerebrovascular Disease. All patients provided informed consent. METHODS: 80-140 mL umbilical blood of term birth of newborn was selected hermetically and maintained in sterile plastic bag. And then, the blood was centrifugated at the speed of 1 500 r/min for 30 minutes at 22 ℃ in order to separate MNC, i.e., HUCBSC. In addition, after final diagnosis during hospitalization, stroke patients were perfused with HUCBSC through superficial vein of back of the hand. Each patient was averagely perfused with 6 portions of HUCBSC (cellular numbers ≥ 1×108/portion) and the interval between each portion was 1-7 days with the mean interval of 4 days. MAIN OUTCOME MEASURES: ① Neurological function of stroke patients was evaluated with neurological function deficiency (NFD) before treatment and at 3 months after treatment. The scale includes consciousness, level fix function, facial paralysis, language, muscle force of upper limbs, muscle force of lower limb and step function. The total scores ranged from 0 to 45; meanwhile, the lower the scores were, the better the neurological function was. ② Motor function of injured limbs was evaluated with Fugl-Meyer Assessment (FMA), including motor function of upper limbs, motor function of lower limbs, balance ability, sensory function and motion of joint. The total scores ranged from 0 to 226; meanwhile, the higher the scores were, the better the motor function of limbs was. ③ Activities of daily living (ADL) was evaluated with Barthel Index (BI), including having meals, taking a bath, dressing oneself, putting on clothes, walking in balance and stair activity. The total scores ranged from 0 to 100; meanwhile, the higher the scores were, the stronger the ADL was. RESULTS: A total of 10 patients were involved in the final analysis. After treatment, NFD of stroke patients was (10.9±5.09) points, which was lower than that before treatment [(25.4±6.09) points, t =8.213, P < 0.01]. In addition, after treatment, FMA and BI of stroke patients were (80.9±25.00) points and (81.1±15.93) points, respectively, which were higher than those before treatment [(31.9±21.85) points, (36.2±19.41) points, t =13.024, 13.670, P < 0.01]. Immuno-suppressive drugs were not used during the whole therapeutic procedure; moreover, immunological rejection and allergic reaction were not observed during the same period. CONCLUSION: Transplanting HUCBSC through superficial vein of back of the hand is regarded as a simple and safe method for the treatment of stroke sequela.

Editor's Choice——Umbilical cord blood mesenchymal stem cell differentiation and transplantation in neural regeneration

Previous in vivo experiments have shown that human umbilical cord blood mesenchymal stem cells can promote the proliferation and differentiation of damaged celts, and help to repair damaged sites, Recent studies have reported that umbilical cord blood-derived mesenchymal stem cells can differentiate into neurons and glial cells. Recent studies have reported that the repair mechanisms underlying cord blood stern cells involve the replacement of damaged cells and mediation of the local micro-environment.

The chimeric mice derived from umbilical cord blood stem cells of EGFP-transgenic mouse

Objective:The chimeric mice were prepared by microinjection of blastocyst cavity using umbilical cord blood stem cells(UCBSCs)of Enhanced Green Fluorescent Protein(EGFP)-transgenic mouse,which was expected to provide a theoretical and experimental basis for the study of in-vivo differentiation of adult stem cells.Methods:Mouse UCBSCs expressing green fluorescence was microinjected into blastocyst cavity and several blastocysts were transferred into uterus of pseudo pregnant mouse.First of all,new-born candidate chimeric mice were observed through feather color.Secondly,the genomic DNA and total RNA were extracted to analyze chimeric rate in several tissues.Finally,flow cytometry was used to detect percentage of green fluorescent cells mice in several tissues.Results:The UCBSCs expressing green fluorescent protein were successfully isolated.After flow cytometry analysis,the proportion of cells expressing green fluorescence was 80.25%.Through microinjection and embryo transfer,we got five white new-born mice and no chimeric feather color was observed.The analyses of PCR and RT-PCR were carried out to detect EGFP gene using six tissues including heart muscle,liver,lung,skin,leg muscle and adipose tissue.The results showed that the leg muscle and adipose tissue of two mice were positive and the other tissues and six tissues of the other 3 mice were all negative.The leg muscle and adipose tissue of two positive mice were digested into single-cells suspension and were carried out flow cytometry analysis.The results showed that the average chimeric rates of leg muscle and adipose tissue of two positive mice were 9.87% and 5.78%,respectively.Conclusions:The results demonstrated that adult UCBSCs could differentiate into leg muscle and adipose tissue in vivo.

Combined use of Y-tube conduits with human umbilical cord stem cells for repairing nerve bifurcation defects

Given the anatomic complexity at the bifurcation point of a nerve trunk,enforced suturing between stumps can lead to misdirection of nerve axons,thereby resulting in adverse consequences.We assumed that Y-tube conduits injected with human umbilical cord stem cells could be an effective method to solve such problems,but studies focused on the best type of Y-tube conduit remain controversial.Therefore,the present study evaluated the applicability and efficacy of various types of Y-tube conduits containing human umbilical cord stem cells for treating rat femoral nerve defects on their bifurcation points.At 12 weeks after the bridging surgery that included treatment with different types of Y-tube conduits,there were no differences in quadriceps femoris muscle weight or femoral nerve ultrastructure.However,the Y-tube conduit group with longer branches and a short trunk resulted in a better outcome according to retrograde labeling and electrophysiological analysis.It can be concluded from the study that repairing a mixed nerve defect at its bifurcation point with Y-tube conduits,in particular those with long branches and a short trunk,is effective and results in good outcomes.

Long-term outcomes in adults with leukemia treated with transplantation of two unrelated umbilical cord blood units

Background Wide application of umbilical cord blood transplantation （UCBT） in adult patients is limited by low cell-dose available in one umbilical cord blood （UCB） unit. The aim of this study was to investigate the safety and long-term outcomes of UCBT from unrelated donors in adult and adolescent patients with leukemia. Methods Thirteen patients with leukemia received double-unit UCBT with human leukocyte antigen （HLA） mismatched at 0-2 loci. We analyzed the engraftment, graft-versus-host disease （GVHD） and survival. Results Twelve evaluable patients （92.3%） had neutrophil and platelet engraftment at a median of 21 days （range, 16-38 days） and 34 days （range, 25-51 days）, respectively. At day 30, engraftment was derived from one donor in 8 patients （66.7%, 95% Cl 40.0%-93.4%）, and from both donors in 4 patients （33.3%, 95% CI 6.7%-60.0%） with 1 unit predominated. Unit with larger nucleated cell （NC） dose would predominate in engraftment （P=-0.039）, whereas CD34~ cell dose or HLA-match failed to demonstrate any relationship with unit predominance. Only one patient developed grade II acute graft-versus-host disease （aGVHD）. Chronic GVHD （cGVHD） was observed in 2 of 11 patients who survived more than 100 days, and both were limited. The median follow-up after transplantation for the 13 patients was 45 months （range 1.5-121.0 months） and 72 months （range 41.0-121.0 months） for the 8 alive and with full donor chimerism. The 5-year cumulative disease free survival （DFS） was （61.5±13.5）%. Of the 13 patients, 5 patients died in 1 year and 1-year transplantation related mortality （TRM） was 23.1% （95% Cl 0.2%-46.0%）. Conclusion Double-unit UCBT from unrelated donors with HLA-mismatched at 0-2 loci may overcome the cell-dose barrier and be feasible for adults and adolescents with leukemia.

Successful transplantation of double unit umbilical-cord blood from unrelated donors in high risk leukemia with a long follow-up

Umbilical-cord blood (UCB) is a source of hematopoietic stem cells that has been successfully used for transplantation, primarily in children. But the low cell dose severely limits the application of unrelated umbilical-cord blood transplantation (UCBT) in adult patients, particularly in those with high body weight. We hypothesized that the combined transplantation of two partially matched UCB units would improve engraftment without crossed immunological rejection. Since May 2000, six adult patients with high risk leukemia have been transplanted in this study.

Comparison of clinical outcomes between unrelated single umbilical cord blood and"ex-vivo"T-cell depleted haploidentical transplantation in children with hematological malignancies

Background Over the last two decades,umbilical cord blood(UCB)and haploidentical transplantation(HaploHSCT)have emerged as alternative sources of hematopoietic stem cell for allogeneic transplantation.There are few retrospective studies and no prospective studies comparing both types of alternative transplantation in pediatric patients.Results We analyzed the data of 134 children with hematological malignancies who received a hematopoietic stem cell transplantation from a single umbilical cord blood(UCB)(n=42)or an"tex-vivo"T-cell depleted transplant from a haploi-dentical-related donor(HaploHSCT)(n=92)between 1996 and 2014.Hematological recovery was faster after HaploHSCT than the UCB transplant group(median times to neutrophil and platelet recovery:13 vs.16 days,10 vs.57 days,respectively)(P<0.001).The HaploHSCT group had a significantly early immune reconstitution based on NK and CD8+T cells compared with the UCB group.However,after the first year post-transplantation.HaploHSCT had a lower number of CD4+ T and B lymphocytes compared with the UCB transplant recipients.The cumulative incidence of TRM was 29±8%in the HaploHSCT group versus 40±5%in the UCB group.Relapse incidence was 21±7%in the HaploHSCT group and 19±8%in the UCB group.Probability of DFS was 58±8%in the HaploHSCT group versus 40±9%in the UCB group(P=0.051).Conclusions TCD haploidentical transplant is associated with advantages in terms of engraftment and early immune reconstitution kinetics.TCD haploidentical transplant was associated with lower incidence of infectious and non-infectious complications,especially in the early phases of the transplant compared with UCB transplant recipients.However,there are no advantages in transplant outcomes compared with UCB transplant.

The impact of HLA haplotype and alleles mismatches of donor-recipient pairs on outcome of haplo-identical hematopoietic stem cell transplantation with a third part cord blood unit

Objective To analyze allele mismatches of HLA-A,-B,-C,-DRB1,-DQB1 and haplotype mismatch of donor-recipient pairs on the outcome of haploidentical transplantation combined with a third part cord blood unit.Methods 230 pairs of donor-recipient were performed HLA-A,B,C,DRB1,DQB1 typing using

Transplantation of human umbilical cord-derived endothelial progenitor cells promotes re-endothelialization of the injured carotid artery after balloon injury in New Zealand white rabbits

Background Cell transplantation has great potential for promoting endothelial repair and reducing the complications of percutaneous coronary intervention （PCI）. The aim of this study was to investigate the effect of transplantation of human umbilical cord blood endothelial progenitor ceils （EPCs） on injured arteries. Methods Umbilical cord blood mononuclear cells were obtained from post-partum lying-in women, and EPCs were isolated, cultured, expanded and identified by immunofiuorescence. The carotid arterial endothelium of New Zealand white rabbits was injured by dilatation with a 3F balloon, and the EPCs were injected into the lumen of the injured artery in the transplanted group （n=16）, while an equal volume of phosphated buffered saline （PBS） was injected into the control group after balloon injury （n=16）. The animals were sacrificed after either 2 or 4 weeks, and the grafted cells were identified by double immunofluorescence staining with human nuclear antigen （HNA） and CD31 antibodies. Arterial cross sections were analyzed by pathology, immunohistochemisty and morphometry to evaluate the reparative effects of EPCs. Proliferating cell nuclear antigen （PCNA） and transforming growth factor （TGF）-131 mRNA expression were detected by reverse transcription-polymerase chain reaction （RT-PCR）. Results Fluorescence-labeled EPCs were found in the neointima. The neointimal area and the neointimal/medial area ratio were significantly lower in the transplanted group than in the control group （P 〈0.05）. von Willebrand factor （vWF） immunohistostaining showed more VWF-positive cells in the transplanted animals than in the controls （8.75±2.92 vs. 4.50±1.77, P 〈0.05）. Compared with the control group, the transplanted group had lower expression of PCNA mRNA （0.67±0.11 vs. 1.25±0.40, P 〈0.01 ）and higher expression of TGF-β1 mRNA （1.10±0.21 vs. 0.82±0.07, P 〈0.05）. Conclusions EPCs derived from human umbilical cord blood were successfully transplanted into injured vessels. The transplanted EPCs inhibited neointimal hyperplasia and promoted vascular re-endothelialization.