Quality-adjusted time without symptoms or toxicity analysis of haploidentical-related donor vs.identical sibling donor hematopoietic stem cell transplantation in acute myeloid leukemia

Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.

The Impact of Blood Transfusion on the Efficiency of Stem Cell Transplants

Background: While blood product transfusion is essential for managing hematologic deficits in Allogenic Hematopoietic stem cell transplant (AHSCT) recipients, it has risks including infectious disease transmission, alloimmunization, and transfusion reactions. These risks have sparked an ongoing debate regarding the overall impact of transfusions on patient outcomes. Thus, this study aimed to evaluate the impact of Red Blood Cells (RBCs) and/or platelet transfusion on the infection incidence and overall survival in AHSCT patients. Methods: We performed a retrospective analysis of clinical and laboratory data of sixty adult patients with primary malignant hematological disorder who had undergone AHSCT. Participants’ data were categorized into two groups;Group 1 (low transfusion group) consisted of patients receiving 10 units. Quantitative data were expressed as mean ± SD. The t-test of significance and Chi-square (χ2) test were used, with p ≤ 0.05 considered significant. Result: A total of 60 patients’ data was included. In Group 1, out of 30 patients, 13 (43.33%) developed infections. In contrast, Group 2 had 21 (70%) out of 30 patients develop infections. Group 1 had a higher survival rate (57.8%) than Group 2 (transfusion > 10 units) (46.2%) with a chi-square value = 23.56, and p-value Conclusion: The volume of blood product transfusions has a considerable impact on patient outcomes, particularly infection and survival rates. Additional long-term prospective studies and larger randomized controlled trials are needed to strengthen the evidence for determining transfusion protocols for these patients.

Development of Non-ABO Red Blood Cell Alloantibodies in Patient Undergoing Allogeneic Haematopoietic Stem Cell Transplant

Alloantibodies that are non ABO Alloimmunization to protein antigens happens only after exposure, in contrast to ABO isohaemagglutinins, which are present naturally, even in the absence of prior exposure. It is recognized that while non-ABO RBC antibodies are less common than ABO antibodies, they generate essentially the same issues that lead to unfavorable clinical results. If non-ABO alloantibodies are identified early on, these issues related complications may be avoided This call for an in-depth understanding of the recipient and donor’s ABO-Rh grouping, antibody screening, and the phenotype of certain antigens. Equally important, the temporal association time between transplantation and hemolysis can help identify the underlying mechanism of hemolysis and direct appropriate management. Therefore, for that, it is crucial to identify the etiology of post-HSCT anemia for prevention and therapy, in addition to a thorough grasp of the mechanism of anemia in non-ABO-incompatible HSCT and the temporal link between HSCT and anemia. Finding the cause of post-HSCT anemia is essential for prevention and therapy, in addition to a thorough grasp of the mechanism of anemia in non-ABO-incompatible HSCT and the temporal link between HSCT and anemia. Therefore, for that, it is crucial to identify the etiology of post-HSCT anemia. In this case report review, we would like to highlight the vital role of transfusion medicine services and stem cell clinical teams in paying particular attention to the clinical significance of non-ABO alloantibodies involved to avoid causing overt hemolysis of incompatible donor RBCs or delayed erythropoiesis. Considering the fact that some of the Haematopoietic stem cell transplant centers do not give an attention to the other non-ABO RBC antigens.

TSR:A User-friendly R Shiny Application for Assessment of Optimal Blood Product Selection in ABO-incompatible Hematopoietic Stem Cell Transplantation

Objective:Patients undergoing hematopoietic stem cell transplant(HSCT)need frequent transfusions,until their red blood cells(RBCs)and platelets start to recover.The safe transfusion for patients who receive ABO-incompatible HSCT is essential to the transplant process.To date,there is no user-friendly tool to choose the right blood product for transfusion treatment,despite the number of guidelines and expert advice on the subject.Methods:R/shiny is a powerful programming language for clinical data analysis and visualization.It can create interactive web applications that work in real-time.The web application named TSR was built using R programming,simplifying blood transfusion practice for ABO-incompatible HSCT witha one-click solution.Results:The TSR is divided into four main tabs.The home tab provides an overview of the application,while RBC,plasma and platelet transfusion tabs offer tailored suggestions for blood product selection in each category.Unlike traditional methods that rely on treatment guidelines and specialist consensus,TSR leverages the power of the R/Shiny interface to extract critical content based on user-specified parameters,providing an innovative approach to improve transfusion support.Conclusion:The present study highlights that the TSR enables real-time analysis,and promotes transfusion practice byoffering a unique and efficient one-key output for blood product selection to ABO-incompatible HSCT.TSR has the potential to become a widely-utilized tool for transfusion services,providing a reliable and user-friendly solution that enhances transfusion safety in clinical practice.

Haploidentical hematopoietic stem cell transplantation as promising therapy in the improved survival of pediatric patients with leukemias and myelodysplasias

BACKGROUND Haploidentical hematopoietic stem cell transplantation(Haplo-HSCT)is often performed in children with hematologic malignancies.Faced with the gap in the literature regarding the approach to experiences related to Haplo-HSCT with pediatric patients with leukemias and myelodysplasias aged up to 18 years,there was an interest in exploring the clinical outcomes of patients undergoing this treatment.AIM To identify and summarize the scientific contributions available on Haplo-HSCT performed in the last 10 years in children and adolescents with myeloid and lymphoid leukemias and myelodysplasias,aged up to 18 years.METHODS This is a descriptive systematic review.We extracted data including characteristics of participants,health condition,characteristics of the donation,conditioning regimen,recurrent clinical complications and clinical outcomes.The Virtual Health Library Brazil,PubMed,EMBASE,and SciELO platforms were used,finding a total of 1052 studies.After the eligibility criteria and complete reading of the texts,18 articles were included for analysis.RESULTS The total sample of all study cohorts was 1825 patients,mostly male,the highest reported median age was 15.0 years and the lowest was 1.2 years.Acute graftversus-host disease and chronic graft-versus-host disease were observed in almost all studies.Relapse,graft rejection and delayed immune recovery were identified as major clinical challenges.Pre-transplant minimal positive residual disease was identified in 288 patients.Infections are also among the main clinical complications,viral,bacterial and fungal infections being reported.It is observed that in the 5-year interval,the lowest rates of EFS and overall survival(OS)were 29.5%and 68.0%,respectively.While,the highest rates of EFS and OS,in the same interval,were 80.1%and 81.0%.CONCLUSION Haplo-HSCT represents a promising therapy,considering the potential number of possible donors and the conditioning and treatment platforms that can be offered.The results obtained show that this type of transplant has a strong antileukemic effect,with generally favorable OS rates.Overcoming relapse as the first cause of transplant failure is the great clinical challenge.

Stem cell transplantation for treatment of cerebral ischemia in rats Effects of human umbilical cord blood stem cells and human neural stem cells

BACKGROUND： Exogenous neural stem cell transplantation promotes neural regeneration. However, various types of stem cells transplantation outcomes remain controversial. OBJECTIVE： To explore distribution, proliferation and differentiation of human neural stem cells （hNSCs） and human umbilical cord blood stem cells （hUCBSCs） following transplantation in ischemic brain tissue of rats, and to compare therapeutic outcomes between hNSCs and hUCBSCs. DESIGN, TIME AND SETTING： Randomized controlled animal studies were performed at the Experimental Animal Center of Nanjing Medical University and Central Laboratory of Second Affiliated Hospital of Nanjing Medical University of China from September 2008 to April 2009. MATERIALS： hNSCs were harvested from brain tissue of 10 13 week old fetuses following spontaneous abortion, and hUCBSCs were collected from umbilical cord blood of full-term newborns at the Second Affiliated Hospital of Nanjing Medical University of China. hNSCs and hUCBSCs were labeled by 5-bromodeoxyuridine （BrdU） prior to transplantation. METHODS： Rat models of cerebral ischemia were established by the suture method. A total of 60 healthy male Sprague Dawley rats aged 7-9 weeks were randomly assigned to hNSC transplantation, hUCBSC transplantation and control groups. The rat models in the hNSC transplantation, hUCBSC transplantation and control groups were infused with hNSC suspension, hUCBSC suspension and saline via the caudal vein, respectively. MAIN OUTCOME MEASURES： The distribution, proliferation and differentiation of hNSCs and hUCBSCs in ischemic brain tissue were observed using immunohistochemical methods. Neurological function in rats was assessed using the neurological severity score. RESULTS： The number of BrdU-positive cells was significantly greater in the hNSC transplantation group compared with hUCBSC transplantation group at 14 days following transplantation （P 〈 0.05） The number of BrdU-positive cells reached a peak at 28 days following transplantation. Nestin-positive, glial fibrillary acidic protein-positive, cyclic nucleotide 3＇ phosphohydrolase-positive and neuron specific enolase-positive cells were visible following transplantation. No significant difference was determined in the constituent ratio of various cells between hNSC and hUCBSC transplantation groups （P 〉 0.05）. The neurological severity score was significantly decreased in rats at 21 days following transplantation （P 〈 0.05）. No significant difference was detected in neurological severity score between hNSC and hUCBSC transplantation groups at various time points （P 〉 0.05）. CONCLUSION： The transplanted hNSCs and hUCBSCs can migrate into ischemic brain tissue, proliferate and differentiate into neuron-like, astrocyte-like and oligodendrocyte-like cells, and improve neurological function in rats with cerebral ischemia.

Human umbilical cord blood stem cell transplantation for the treatment of chronic spinal cord injury Electrophysiological changes and long-term efficacy

Stem cell transplantation can promote functional restoration following acute spinal cord injury （injury time 〈 3 months）, but the safety and long-term efficacy of this treatment need further exploration. In this study, 25 patients with traumatic spinal cord injury （injury time 〉 6 months） were treated with human umbilical cord blood stem cells via intravenous and intrathecal injection. The follow-up period was 12 months after transplantation. Results found that autonomic nerve functions were restored and the latent period of somatosensory evoked potentials was reduced. There were no severe adverse reactions in patients following stem cell transplantation. These experimental findings suggest that the transplantation of human umbilical cord blood stem cells is a safe and effective treatment for patients with traumatic spinal cord injury

Allogeneic Peripheral Blood Hematopoietic Stem Cell Transplantation for Patients with Hematologic Malignancies

To investigate the therapeutic effects and associated complications of allogeneic peripheral blood stem cell transplantation （allo-PBSCT）, 40 patients with various malignant hematopoietic diseases received allo-PBSCT. The preparative regimens were based on BUCY2 or modified BUCY2, The acute graft-versus host disease （aGVHD） was prevented by cyclosporin A and shortterm MTX regimen in all patients. Two patients from donors with one fully mismatched HLA on DRB1 locus and 4 from unrelated donor also administered Zenapox （CD25 MAb） at dosage of 1 rag/ kg every day on the day before transplantation and day 4 after transplantation. These 6 patients were also treated with mycophenolate mofetil （MMF）. Transfusion of the donor cells： The median of the transfused nucleated cells was 5.38×10^8/kg and that of the CD34^＋ cells was 7.8×10^6/kg respectively. All the patients gained hematopoietic reconstruction except one who died of infection before engraftment. Seven patients got Ⅱ°-Ⅳ° aGVHD and the incidence was 17.5 %. Fourteen patients got cGVHD and the incidence was 53.8 % in the patients who survived over 6 months. Twenty-eight patients had fever or other characteristics of infection. The median follow-up time was 13.8 months. The incidence of transplantation related mortality （TRM） was 17.5 %and 2 patients relapsed （5.0 %）. It was concluded that allo-PBSCT can reconstruct hematopoiesis quickly and is a favorable therapeutic method for leukemia.

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.

Day 100 Absolute Monocyte/Lymphocyte Prognostic Score and Survival Post Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation in Diffuse Large B-Cell Lymphoma

Day 100 prognostic factors post-autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) to predict clinical outcomes in diffuse large B-cell lymphoma (DLBCL) patients have not been studied. Thus, we retrospectively examined if day 100 absolute monocyte/lymphocyte prognostic score (AMLPS-100) affects clinical outcomes by landmark analysis from day 100 post-APBHSCT in DLBCL. Only DLBCL patients in complete remission at day 100 post-APBHSCT were evaluated. From 2000 to 2007, 134 consecutive DLBCL patients are qualified for the study. Patients with a day 100 absolute monocyte count (AMC-100) ≥ 630 cells/μL and day 100 absolute lymphocyte count (ALC-100) ≤ 1000 cells/μL experienced inferior overall survival (OS) and progression free survival (PFS). On multivariate analysis, the AMC-100 and ALC-100 remained independent predictors of OS and PFS. Combining both values into the AMLPS-100, the 5-year OS rates for low, intermediate, and high AMLPS-100 risk groups were 94% (95% CI, 83.0% - 98.1%), 70% (95% CI, 58.6% - 80.1%), and 13% (95% CI, 3.4% - 40.5%), respectively;and the 5-year PFS rates were 87% (95% CI, 74.0% - 94.1%), 68% (95% CI, 56.0% - 77.8%), and 13% (95% CI, 3.4% - 40.5%), respectively. The AMLPS-100 is a simple biomarker score that can stratify clinical outcomes from day 100 post-APBHSCT in DLBCL patients.

A Multi-Center International Survey Related to the Nutritional Support after Hematopoietic Stem Cell Transplantation Endorsed by the ASIA Pacific Blood and Marrow Transplantation (APBMT)

Background: The nutritional support after hematopoietic stem cell transplantation (HSCT) has not been well established due to the scarcity of clinical trials. To conduct international clinical trials in Asia, we performed the questionnaire survey to investigate the current standard of nutritional support after HSCT. Method: We sent the questionnaire to the physicians nominated by the Asia Pacific Blood and Marrow Transplantation (APBMT) members of each country/ region. Result: We received 15 responses from 7 different countries/regions. The target calorie amount is 1.0 - 1.3 × basal energy expenditure (BEE) in 11 institutes when partial parenteral nutrition is used. When total parenteral nutrition (TPN) is used, the target calorie amount is 1.0 - 1.3 × BEE in 9 institutes and 1.3 - 1.5 × BEE in 4 institutes. Lipid emulsion is routinely used in 12 institutes. Multivitamins and trace elements are routinely added to TPN used in most institutes. It is still uncommon to use the immunonutrition. Blood glucose levels are routinely monitored in all institutes, but the target range varies (<110 in 2 institutes, <150 in 4 institutes, and <200 in 8 institutes). Conclusions: Basic nutritional support is similar in participating institutes. However, the target glucose level varies and the use of immunonutrition is rather rare. These points can be the theme of future clinical trials.

Clinical Utility of Molecular Diagnosis of Blood Stream Infections in Allogeneic Hematopoietic Stem Cell Transplantation Recipients with Hematologic Malignancies

Blood stream infections (BSIs) are a serious problem in patients with hematologic malignancies receiving allogeneic hematopoietic stem cell transplantation (ASCT). We evaluated the clinical utility of molecular diagnosis for the management of BSIs in such patients. We prospectively performed a polymerase chain reaction (PCR) analysis of microbial DNA in blood samples from 10 consecutive patients with hematological malignancies at least once a week for one month after ASCT. In total, 51 and 54 samples were analyzed by bacterial and fungal PCR assays, respectively. Bacteria were detected in 24 samples from 8 patients by PCR, but in only 2 samples from one patient by blood culture. Notably, the bacteria detected in at least half of the 24 samples were considered to have originated from the oral cavity. Fungi were detected in 5 samples from 3 patients by PCR, but not by blood culture. Most cases with positive PCR results were manageable with empirical antimicrobial therapy without disclosure of DNA data. Our DNA analyses did not directly contribute to management of BSIs, but did provide valuable microbiological evidence for the patients. Additionally, oral management appears to require a critical re-evaluation to reduce the occurrence of BSIs in ASCT recipients.

Efficacy of peripheral blood stem cell transplantation versus conventional chemotherapy on anaplastic large-cell lymphoma:a retrospective study of 64 patients from a single center

Anaplastic large-cell lymphoma(ALCL) is characterized by frequently presenting adverse factors at diagnosis.Many groups believed aggressive treatment strategies such as autologous stem cell transplantation brought survival benefit for ALCL patients.However,few compared these approaches with conventional chemotherapy to validate their superiority.Here,we report a study comparing the efficacy of peripheral blood stem cell transplantation(PBSCT) and conventional chemotherapy on ALCL.A total of 64 patients with primary systemic ALCL were studied retrospectively.The median follow-up period was 51 months(range,1-167 months).For 48 patients undergoing conventional chemotherapy only,the 4-year event-free survival(EFS) and overall survival(OS) rates were 70.7% and 88.3%,respectively.Altogether,16 patients underwent PBSCT,including 11 at first remission(CR1/PR1),3 at second remission,and 2 with disease progression during first-line chemotherapy.The 4-year EFS and OS rates for patients underwent PBSCT at first remission were 81.8% and 90.9%,respectively.Compared with conventional chemotherapy,PBSCT did not show superiority either in EFS(P = 0.240) or in OS(P = 0.580) when applied at first remission.Univariate analysis showed that patients with B symptoms(P = 0.001),stage III/IV disease(P = 0.008),bulky disease(P = 0.075),negative anaplastic lymphoma kinase(ALK) expression(P = 0.059),and age ≤ 60 years(P = 0.054) had lower EFS.Furthermore,PBSCT significantly improved EFS in patients with B symptoms(100% vs.50.8%,P = 0.027) or bulky disease(100% vs.52.8%,P = 0.045) when applied as an up-front strategy.Based on these results,we conclude that,for patients with specific adverse factors such as B symptoms and bulky disease,PBSCT was superior to conventional chemotherapy in terms of EFS.

CYTOMEGALOVIRUS INTERSTITIAL PNEUMONITIS FOLLOWING ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION

Objective： To explore the risk factors and prophylaxis and treatment of cytomegalovirus interstitial pneumonitis （CMV-IP） after allogeneic peripheral blood stem cell transplantation （allo-PBSCT）. Methods： 43 patients who received allo-PBSCT were allocated to either a Gancyclovir（GCV）-prophylaxis group （n=19） or a non-GCV prophylaxis group （n=24）. A comparison was made of the incidence of CMV-IP in patients given or not given prophylactic gancyclovir. Results： 9 patients in non-GCV prophylaxis group developed late CMV-IP （P〈0.05）. Graft-versus-host-disease （GVHD） may be associated with a high risk of CMV-IP. 5 cases of CMV-IP were successfully treated with GCV, but 3 cases died of CMV-IP. The most common adverse event of GCV was neutropenia, but was reversible. Conclusion： CMV infection was a major cause of interstitial pneumonitis after allo-PBSCT, which correlated strongly with the severity of GVHD. Gancyclovir was shown to be effective in both prophylaxis and treatment of CMV-IP.

How old is too old? In vivo engraftment of human peripheral blood stem cells cryopreserved for up to 18 years-implications for clinical transplantation and stability programs

BACKGROUND Peripheral blood stem cells(PBSC)are commonly cryopreserved awaiting clinical use for hematopoietic stem cell transplant.Long term cryopreservation is commonly defined as five years or longer,and limited data exists regarding how long PBSC can be cryopreserved and retain the ability to successfully engraft.Clinical programs,stem cell banks,and regulatory and accrediting agencies interested in product stability would benefit from such data.Thus,we assessed recovery and colony forming ability of PBSC following long-term cryopreservation as well as their ability to engraft in NOD/SCID/IL-2 Rγnull(NSG)mice.AIM To investigate the in vivo engraftment potential of long-term cryopreserved PBSC units.METHODS PBSC units which were collected and frozen using validated clinical protocols were obtained for research use from the Cellular Therapy Laboratory at Indiana University Health.These units were thawed in the Cellular Therapy Laboratory using clinical standards of practice,and the pre-freeze and post-thaw characteristics of the units were compared.Progenitor function was assessed using standard colony-forming assays.CD34-selected cells were transplanted into immunodeficient mice to assess stem cell function.RESULTS Ten PBSC units with mean of 17 years in cryopreservation(range 13.6-18.3 years)demonstrated a mean total cell recovery of 88%±12%(range 68%-110%)and post-thaw viability of 69%±17%(range 34%-86%).BFU-E growth was shown in 9 of 10 units and CFU-GM growth in 7 of 10 units post-thaw.Immunodeficient mice were transplanted with CD34-selected cells from four randomly chosen PBSC units.All mice demonstrated long-term engraftment at 12 wk with mean34%±24%human CD45+cells,and differentiation with presence of human CD19+,CD3+and CD33+cells.Harvested bone marrow from all mice demonstrated growth of erythroid and myeloid colonies.CONCLUSION We demonstrated engraftment of clinically-collected and thawed PBSC following cryopreservation up to 18 years in NSG mice,signifying likely successful clinical transplantation of PBSC following long-term cryopreservation.

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.

Hematopoiesis reconstitution and anti-tumor effectiveness of Pai-Neng-Da capsule in acute leukemia patients with haploidentical hematopoietic stem cell transplantation

BACKGROUND With the rapid development of haploidentical hematopoietic stem cell transplantation(haplo-HSCT),primary poor graft function(PGF)has become a lifethreatening complication.Effective therapies for PGF are inconclusive.New Chinese patent medicine Pai-Neng-Da(PND)Capsule exerts dual effect in promoting hematopoiesis recovery and regulating immunity.Still,the application of PND capsule in hematopoietic stem cell transplantation,especially in the haplo-HSCT setting,has not yet been reported.AIM To evaluate the role of PND capsule in acute leukemia patients with haplo-HSCT.METHODS We retrospectively collected data of acute leukemia patients who underwent haplo-HSCT at the Affiliated People’s Hospital of Ningbo University between April 1,2015 and June 30,2020.Twenty-nine consecutive patients received oral PND capsule from the sixth day to the first month after haplo-HSCT were included in the PND group.In addition,31 patients who did not receive PND capsule during haplo-HSCT were included in the non-PND group.Subsequently,we compared the therapeutic efficacy according to the western medical evaluation indexes and Chinese medical symptom scores,and the survival between the PND group and the non-PND group,using the chi-square test,Fisher’s exact test,and the Kaplan-Meier method.RESULTS The duration of platelet engraftment was shorter in the PND group than in the non-PND group(P=0.039).The PND group received a lower frequency of red blood cells and platelet transfusions than the non-PND group(P=0.033 and P=0.035,respectively).In addition,PND capsule marginally reduced the rate of PGF(P=0.027)and relapse(P=0.043).After 33(range,4-106)months of follow-up,the 3-year relapse-free survival(P=0.046)and progression-free survival(P=0.049)were improved in the PND group than in the non-PND group.Also,the therapeutic efficacy of the PND group according to Chinese medical symptom scores was significantly better than that of the non-PND group(P=0.022).Moreover,the adverse events caused by PND capsule were mild.Nevertheless,there were no significant differences in the duration of neutrophil engraftment,the risk of infection within 100 days after haplo-HSCT,the acute graft-versus-host disease,or the 3-year overall survival between the two groups.CONCLUSION PND capsule could promote hematopoiesis reconstitution,improve the therapeutic efficacy of Chinese medical symptom scores,present anti-tumor effectiveness,and prolong the survival of acute leukemia patients with haplo-HSCT.

Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation for Thymoma-associated Severe Aplastic Anemia: a Case Report

THYMOMA, a relatively rare epithelial neoplasm with unique clinical and pathologic features, is the most usual diagnosis for a mass located in the mediastinum. It is often associated withautoimmune disorders. The myastnema gravls ano pure red cell aplasia are the most common disorders, with the incidences of 40% and 5%, respectively, while the incidence of aplastic anemia is only about 0-1.4%. 1 Thymectomy is hard to perform on patients with severe aplastic anemia（SAA） due to severe pancytopenia.

Haploidentical stem cell transplantation used in treating primary plasma cell leukemia: a case report

Here we report a successful protocol in treatment of a patient with primary plasma cell leukemia (PPCL) using haploidentical stem cell transplantation (hi-HSCT). During first complete remission after routine chemotherapy, the patient received autologous blood stem cell transplantation, but he had relapse later. He gained a second CR after chemotherapy and underwent hi-HSCT from his daughter, who had HLA mismatched at three loci. Recovery of hemopoiesis was found at day 14 and complete donor chimerism was confirmed by PCR-STR on day 34, 95 and 238. The patients have survived disease-free for 56 months since hi-HSCT, without serious graft-versus-host-disease.

The safety of autologous peripheral blood stem cell transplantation by intracoronory infusionin in patients with acute myocardial infarction

Objective Bone-marrow stem-cell transplantation has been shown to improve cardiac function in patients with AMI, but the safety of intracoronory infusion of autologous peripheral blood stem-cell(PBSCs) in patients with AMI is unknown. For this reason, we observe the feasibility and safety of PBSCs transplantation by intracoronory infusion in such patients.Method Fourty one patients with AMI were allocated to receive Granulocyte Colony-Stimulating Factor (G-CSF:Filgrastim,300 μg) with the dose of 300 μg-600 μg/day to mobilize the stem cell, and the duration of applying G-CSF was 5 days . On the sixth day, PBSCs were separated by Baxter CS 3000 blood cell separator into suspend liquid 57 ml. Then the suspend liquid was infused into the infarct related artery (IRA)by occluding the over the wire balloon and infusing artery through balloon center lumen. In the process of the intracoronary infusion of PBSCs, the complications should be observed, which were arrhythmias including of bradycardia, sinus arrest or atrial ventricular block, premature ventricular beats ,ventricular tachycardia, ventricular fibrillation; and hypotention, etc. Results There were total 10 cases with complications during the intracoronary infusion of PBSCs. The incidence of complications was 24.4%(10/41), including bradycardia is 2.4 %(1/41), sinus arrest or atrial ventricular block is 4.9%(2/41), ventricular fibrillation is 2.4 %( 1/41), hypotention is14.6 % (6 /41).Conclusions In patients with AMI, intracoronary infusion of PBSCs is feasible and safe.