scholarly journals Feasibility of reduced-dose posttransplant cyclophosphamide and cotransplantation of peripheral blood stem cells and umbilical cord-derived mesenchymal stem cells for SAA

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yingling Zu ◽  
Jian Zhou ◽  
Yuewen Fu ◽  
Baijun Fang ◽  
Xinjian Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Peripheral Blood ◽  
Control Cohort ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Reduced Dose ◽  
Blood Stem Cells ◽  
The Times

AbstractPosttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis is an effective strategie for patients receiving matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) and haploidentical HSCT (haplo-HSCT). We evaluated the effectiveness and safety of reduced-dose cyclophosphamide, 20 mg/kg for 13 patients in MSD-HSCT cohort and 25 mg/kg for 22 patients in haplo-HSCT cohort, on days + 3, + 4 combined with cotransplantation of peripheral blood stem cells (PBSCs) and human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for severe aplastic anemia (SAA). In MSD-PTCy cohort, the times to neutrophil and platelet engraftment were significantly shorter than those in the MSD-control cohort (P < 0.05). The cumulative incidence of acute GVHD (aGVHD) at day + 100 (15.4%) was lower than that in the MSD-control cohort (P = 0.050). No patient developed chronic GVHD (cGVHD). The 1-year overall survival (OS) and event-free survival (EFS) rates were 100% and 92.3%. In haplo-PTCy cohort, the times to neutrophil and platelet engraftment were significantly shorter than those in the haplo-control cohort (P < 0.05). The cumulative incidences of aGVHD at day + 100 and 1-year cGVHD were 31.8% and 18.2%, and the 1-year OS and EFS rates were 81.8% and 66.9%. Reduced-dose PTCy and cotransplantation of PBSCs and UC-MSCs is an acceptable alternative to patients with SAA.

Reduced-dose of Posttransplant Cyclophosphamide and Cotransplantation of Peripheral Blood Stem Cells and Human Umbilical Cord-derived Mesenchymal Stem Cells in Severe Aplastic Anemia

2020 ◽  
Author(s):  
Yingling Zu ◽  
Jian Zhou ◽  
Yuewen Fu ◽  
Baijun Fang ◽  
Xinjian Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Aplastic Anemia ◽  
Peripheral Blood ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Peripheral Blood Stem Cells ◽  
Reduced Dose ◽  
Blood Stem Cells ◽  
The Times

Abstract Background Posttransplant cyclophosphamide (PTCY) as graft-versus-host disease (GVHD) prophylaxis is an effective strategie for patients receiving matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) and haploidentical HSCT (haplo-HSCT). Methods We evaluated the effectiveness and safety of reduced-dose cyclophosphamide, 20 mg/kg for 13 patients in the MSD-HSCT group and 25 mg/kg for 22 patients in the haplo-HSCT group, on days +3 and +4 combined with cotransplantation of peripheral blood stem cells (PBSCs) and human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for patients with severe aplastic anemia (SAA) retrospectively. Results In the MSD-PTCY group, the times to neutrophil and platelet engraftment were significantly shorter than those in the MSD-control group (P<0.05), 11 (range 10 to 14) days and 12 (range 9 to 15) days. The cumulative incidence of acute GVHD (aGVHD) at day +100 (15.4%) was lower in the MSD-PTCY group than in the MSD-control group(P=0.050). No patient developed chronic GVHD (cGVHD). The 1-year overall survival (OS) and event-free survival (EFS) rates in the MSD-PTCY group were 100% and 92.3%. In the haplo-PTCY group, the times to neutrophil and platelet engraftment were significantly shorter than those in the haplo-control group (P<0.05), 12 (range 9 to 15) days and 11.5 (range 9 to 17) days. The cumulative incidences of aGVHD at day +100 and 1-year cGVHD in the haplo-PTCY group were 31.8% and 18.2%. The 1-year OS and EFS rates in the haplo-PTCY group were 81.8% and 66.9%. Conclusions Reduced-dose PTCY and cotransplantation of PBSCs and UC-MSCs is feasible for patients with SAA, especially for overcoming the high incidences of aGVHD and cGVHD due to PBSCs.

scholarly journals Co-transplantation of umbilical cord mesenchymal stem cells and peripheral blood stem cells in children and adolescents with refractory severe aplastic anemia

2021 ◽  
Author(s):  
fangfang Yuan ◽  
MingYue Zhao ◽  
Nan Ma ◽  
Shanggang Zong ◽  
Gangping Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Aplastic Anemia ◽  
Children And Adolescents ◽  
Umbilical Cord ◽  
Peripheral Blood ◽  
Severe Aplastic Anemia ◽  
Donor Group ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells

Objectives: The purpose of our study was to analyze the co-transplantation efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) and peripheral blood stem cells (PBSCs), which is considered as a novel approach for refractory severe aplastic anemia (RSAA) in children and adolescents. Methods: Thirty-two children and adolescents with RSAA were retrospectively reviewed. According to the source of PBSCs, all patients were divided into two groups (matched sibling donor group and matched unrelated donor group). Engraftment, graft-versus-host disease (GVHD) and overall survival (OS) were analyzed. Results: No adverse events related to UC-MSCs infusion occurred in all patients. The median time for neutrophil engraftment was 13 (10~23) days and 15 (11~28) days for platelet. Grade Ⅰ ~ Ⅱ acute GVHD and moderate chronic GVHD were observed in 21.88% and 12.50% of the cases. No statistically significance was observed between the MSD and MUD group on engraftment, GVHD and complications including infection and hemorrhagic cystitis. The median follow-up time was 38.60 (1.37~140.83) months. To the date of October 31th 2021, 5 died and 27 (84.38%) survived. The 5-year OS rate was not statistically significant between the MSD and MUD group (84.8% ± 10.0% vs 82.4% ± 9.2%, P = 0.674). Conclusions: The application of UC-MSCs in the treatment of RSAA in PBSC transplantation is reliable and safe, which can significantly reduce the incidence of GVHD and severe transplantation-related complications and effectively improve patients’ life quality. Therefore, the method can be used as an active treatment option for patients with RSAA.

scholarly journals Timing of Peripheral Blood Stem Cell Yield: Comparison of Alternative Methods with the Classic Method for CD34+Cell Determination

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
I. Fatorova ◽  
M. Blaha ◽  
M. Lanska ◽  
D. Vokurkova ◽  
V. Rezacova ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Reference Method ◽  
Roc Curves ◽  
Alternative Methods ◽  
Optimal Timing ◽  
Hematopoietic Tissue ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Blood Stem Cells

Hematopoietic stem cells (HSCs), still represent a certain mystery in biology, have a unique property of dividing into equal cells and repopulating the hematopoietic tissue. This potential enables their use in transplantation treatments. The quality of the HSC grafts for transplantation is evaluated by flow cytometric determination of the CD34+cells, which enables optimal timing of the first apheresis and the acquisition of maximal yield of the peripheral blood stem cells (PBSCs). To identify a more efficient method for evaluating CD34+cells, we compared the following alternative methods with the reference method: hematopoietic progenitor cells (HPC) enumeration (using the Sysmex XE-2100 analyser), detection of CD133+cells, and quantification of aldehyde dehydrogenase activity in the PBSCs. 266 aphereses (84 patients) were evaluated. In the preapheretic blood, the new methods produced data that were in agreement with the reference method. The ROC curves have shown that for the first-day apheresis target, the optimal predictive cut-off value was 0.032 cells/mL for the HPC method (sensitivity 73.4%, specificity 69.3%). HPC method exhibited a definite practical superiority as compared to other methods tested. HPC enumeration could serve as a supplementary method for the optimal timing of the first apheresis; it is simple, rapid, and cheap.

scholarly journals Isolation and storage of peripheral blood hematopoietic stem cells for autotransplantation into children with cancer

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1245-1251 ◽  
Author(s):  
Y Takaue ◽  
T Watanabe ◽  
Y Kawano ◽  
T Koyama ◽  
T Abe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Platelet Rich Plasma ◽  
Substantial Reduction ◽  
Separation Procedure ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Blood Stem Cells ◽  
Cellular Components ◽  
And Storage

Abstract Peripheral blood stem cells (PBSC) were collected for autotransplantation by a total of 46 continuous-flow leukaphereses in 17 children with various types of cancer in whom the stem-cell pool had been expanded by chemotherapy. As the cells collected by leukapheresis were contaminated with many visible cell clumps, platelets, and erythrocytes, they were separated from the platelet-rich plasma (PRP) by slow-speed centrifugation and fractionated on a discontinuous gradient of Percoll. All the hematopoietic progenitors (CFU-GM, CFU- GEMM) in the starting samples were recovered at the interface of 40% and 60% Percoll solutions largely free of other cellular components and with a substantial reduction in volume. The separation and freezing procedures could be completed within three hours after obtaining cells by leukapheresis. After their fractionation and storage, these PBSC were shown to be able to reconstitute normal hematopoiesis in ten children with poor prognosis leukemia or neuroblastoma for whom no HLA- compatible marrow donors were available and who had been subjected to marrow-ablative therapy. This separation procedure is simple, efficient, and readily available and can be used for children as a routine procedure for PBSC autotransplantation.

Efficient and Durable Gene Marking of Hematopoietic Progenitor Cells in Nonhuman Primates After Nonablative Conditioning

Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2271-2286 ◽  
Author(s):  
M. Rosenzweig ◽  
T.J. MacVittie ◽  
D. Harper ◽  
D. Hempel ◽  
R.L. Glickman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Nonhuman Primates ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Blood Stem Cells ◽  
High Level

Optimization of mobilization, harvest, and transduction of hematopoietic stem cells is critical to successful stem cell gene therapy. We evaluated the utility of a novel protocol involving Flt3-ligand (Flt3-L) and granulocyte colony-stimulating factor (G-CSF) mobilization of peripheral blood stem cells and retrovirus transduction using hematopoietic growth factors to introduce a reporter gene, murine CD24 (mCD24), into hematopoietic stem cells in nonhuman primates. Rhesus macaques were treated with Flt3-L (200 μg/kg) and G-CSF (20 μg/kg) for 7 days and autologous CD34+ peripheral blood stem cells harvested by leukapheresis. CD34+ cells were transduced with an MFGS-based retrovirus vector encoding mCD24 using 4 daily transductions with centrifugations in the presence of Flt3-L (100 ng/mL), human stem cell factor (50 ng/mL), and PIXY321 (50 ng/mL) in serum-free medium. An important and novel feature of this study is that enhanced in vivo engraftment of transduced stem cells was achieved by conditioning the animals with a low-morbidity regimen of sublethal irradiation (320 to 400 cGy) on the day of transplantation. Engraftment was monitored sequentially in the bone marrow and blood using both multiparameter flow cytometry and semi-quantitative DNA polymerase chain reaction (PCR). Our data show successful and persistent engraftment of transduced primitive progenitors capable of giving rise to marked cells of multiple hematopoietic lineages, including granulocytes, monocytes, and B and T lymphocytes. At 4 to 6 weeks posttransplantation, 47% ± 32% (n = 4) of granulocytes expressed mCD24 antigen at the cell surface. Peak in vivo levels of genetically modified peripheral blood lymphocytes approached 35% ± 22% (n = 4) as assessed both by flow cytometry and PCR 6 to 10 weeks posttransplantation. In addition, naı̈ve (CD45RA+and CD62L+) CD4+ and CD8+cells were the predominant phenotype of the marked CD3+ T cells detected at early time points. A high level of marking persisted at between 10% and 15% of peripheral blood leukocytes for 4 months and at lower levels past 6 months in some animals. A cytotoxic T-lymphocyte response against mCD24 was detected in only 1 animal. This degree of persistent long-lived, high-level gene marking of multiple hematopoietic lineages, including naı̈ve T cells, using a nonablative marrow conditioning regimen represents an important step toward the ultimate goal of high-level permanent transduced gene expression in stem cells.

Haplo-Identical Allogeneic Stem Cell Transplantation Using GCSF-Mobilized Marrow Plus Blood Stem Cells from Parent Donors for Children with High-Risk Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5084-5084
Author(s):  
Quanyi Lu ◽  
Xiaoqing Niu ◽  
Peng Zhang ◽  
Delong Liu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Blood Stem Cells

Abstract Increasing number of patients in China have difficulty of finding sibling donors due to limited number of siblings. We therefore explored the feasibility using haploidentical parent donors for allogeneic hematopoietic stem cell transplantation. Eight leukemia patients were studied in our hospital. These included 2 CML-BC, 2 MDS-RAEB, 3 relapsed ALL and 1 relapsed AML. The median age was 12 (7–17). GCSF- mobilized bone marrow and peripheral blood stem cells were collected from parents (1 to 3 locus mismatched). The conditioning regimen consisted of fludarabine (30mg/m2/d x5), bulsulfan (4mg/kg/d x3) and cyclophosphamide (50mg/kg/d x2). Cyclosporin A, mycophenolate mofetil, methotrexate, and ATG were used for GVHD prophylaxis. The total number of CD34+ cell in the grafts ranged between 5–10 x 106/kg. The median follow- up was 13 months (6–24). One patient failed to engraft, the other 7 patients achieved full donor chimerism at day 28. The incidence of acute GVHD (grade II-IV) was 57.1% (4 of 7). The incidence of chronic GVHD of limited stage occurred in the same 4 patients. One patient died of lung complication at 17th month, another patient with CML-BC relapsed 10 months after transplantation. The rest 6 patients are alive without disease. These results suggested that parents could be considered as stem cell donors in the absence of alternative donors for young patients with high-risk diseases. GCSF-primed bone marrow plus peripheral blood stem cells might be beneficial to reduce the risk of GVHD for leukemia children in China. More patients are needed to further study this approach.

Collection of Peripheral Blood Stem Cells in 118 Small Children Weighing 20 Kg or less: Experience of a Single Centre

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3378-3378
Author(s):  
Jianyun Wen ◽  
Yuelin He ◽  
Libai Chen ◽  
Jing Du ◽  
Zhiyong Peng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Thalassemia Major ◽  
Median Number ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Small Children ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Background: Peripheral blood stem cells (PBSC) are increasingly used as a source of stem cells for either autologous or allogeneic hematopoietic transplantation in children.Although technically similar to adult procedures, PBSC harvest may be difficult in young children, especially in the very small children. Aim: In this study, we aimed to evaluatethe safety and efficacy of harvesting peripheral blood hematopoietic stem cells in very small children,and to provide a guideline. Methods: Between Jan 2013 to Mar 2016, we evaluated 118 children weighing 20 kg or less, with the smallest patient weighing 11 kg. The patients had a median age of 59 months and included 72 children with thalassemia major and 46 young donors. The granulocyte-colony stimulating factor (G-CSF) analogs were used at a dose of 10 mg/kg/day administered subcutaneously once a day and receiving oral calcium for five days before harvesting. Blood was withdrawn at a mean rate of 30-40 ml/min through a temporaryfemoral vein catheter (12 or 14 guage) to ensure adequate blood flow and returned through a larger catheter in a peripheral vein.Total nucleated cells(TNC) and CD34+ cells were estimated in the peripheral blood before collection of the apheresis product. Results: We collected sufficient products from all the children with one to three apheresis procedures. No serious complication was detected in all children and all aphereses were completed within 4 hours.The volume of blood per kilogram processed for each apheresis ranged from 55 to 160ml (median, 85ml). The median number of TNC and CD34+ cells collected were 12×108/kg and 15×106/kg per apheresis, respectively. Conclusions:We conclude that collection of PBSC is a safe and practical procedure in children, even in very small children. Disclosures No relevant conflicts of interest to declare.

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