a Feasibility Study of the Full Outpatient Conduction of Hematopoietic Transplants in Persons with Multiple Sclerosis Employing Autologous Non-Cryopreserved Peripheral Blood Stem Cells

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2262-2262
Author(s):  
Guillermo J. Ruiz-Arguelles ◽  
Andrés A. León-Peña ◽  
Mónica León-Gonzalez ◽  
Ana Karen Núñez-Cortés ◽  
Merari Starlight Torres-Priego ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Peripheral Blood ◽  
Outpatient Basis ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Minute Period ◽  
Cd34 Cells ◽  
Blood Stem Cells ◽  
Edss Score

Abstract Background: With the goal of immune system reset, autologous hematopoietic stem cell transplantations have been done in patients with multiple sclerosis (MS). Material and methods: 131 consecutive patients with MS were autografted in a single center using non-frozen peripheral blood stem cells (PBSC) on an outpatient basis and conditioning with cyclophosphamide (Cy) and rituximab. The protocol was registered in ClinicalTrials.gov identifier NCT02674217. The PBSC mobilization schedule was done with Cy and filgrastim (G-CSF). Intravenous Cy (50 mg/Kg) was delivered on days - 11 and - 10. Subcutaneous G-CSF (10 ug / Kg / bid) was delivered on days - 9 to - 1.. The apheresis procedure was performed on day - 2. The apheresis objective was to reach at least 1 x 106 viable CD34+ cells/Kg. As outpatients and after collecting the PBSC, intravenous Cy (50 mg / Kg) was delivered along a 120 minute period, on days - 2 and - 1 followed by MESNA (1000 mg/m2 along a 180-minute period). After the intravenous Cy, oral ondansetron), oral cotrimoxazole, oral fluconazole and oral acyclovir were used in all patients until granulocytes were greater than 0.5 x 109/L. After the recovery of the granulocytes, patients were given rituximab (375 mg/m2 along a 3 h period) and subsequently rituximab (100 mg) every two months along a 12-month period. The cumulative dose of Cy is 200 mg/Kg. Results: 80 females and 51 males were included; median age was 47 years. All procedures were started on an outpatient basis and two persons were admitted to the hospital during the procedure. In order to obtain at least 1 x106 / Kg viable CD34 cells, one to four apheresis were performed (median 1). Total number of viable CD34+ cells infused ranged between 1 and 9.6 x106 / Kg (median 2.2). Patients recovered above 0.5 x109/L absolute granulocytes on median day 9 (range 6 to 12). Two individuals needed red blood cells but none needed platelet transfusions. There were no transplant related deaths, the 120-month overall survival being 100%. In a subset of 25 persons followed for 5 months or more the EDSS was assessed three months after the graft and means diminished from 5.4 to 4.9. The EDSS score improved in 11 patients (44%), remained stable in 7 (28%) and worsened in 7 (28%). A tendency to diminish the EDSS score as a function of time after the autograft was observed in this subset of individuals. Conclusions: It is possible to conduct autotrasplants for patients with MS employing non-frozen peripheral blood stem cells and outpatient conduction. Additional information is needed to assess the efficacy of these procedures in the treatment of patients with MS. Disclosures No relevant conflicts of interest to declare.

Outpatient Hematopoietic Grafting in Patients with Multiple Sclerosis Employing Autologous Non-Cryopreserved Peripheral Blood Stem Cells: A Feasibility Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5489-5489
Author(s):  
Guillermo J. Ruiz-Arguelles ◽  
Andrés León-Peña ◽  
Emilio Medina-Ceballos ◽  
Alejandro Ruiz-Arguelles ◽  
Manuel A Ruiz-Delgado ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
High Dose ◽  
Outpatient Basis ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Background: Multiple sclerosis (MS) is a chronic, inflammatory, debilitating disease that causes destruction of central nervous system (CNS) myelin, with varying degrees of axonal damage. With the goalofd re-setting the immune system, autologous hematopoietic stem cell transplantations (HSCT) have been done in patients with MS since 1996 and more than 700 HSCTs have been performed around the world. The risk of transplant related mortality in HSCT for MS has declined over the past years. Material and methods: Consecutive patients with MS were autografted in a single center using: Hematopoietic stem cells (HSC) were mobilized with cyclophosphamide (Cy), 3 gr/m2 and G-CSF, the procedure was conducted on outpatient basis employing peripheral blood non-frozen HSC and conditioning with high-dose Cy (100 mg/Kg) and post-transplant G-CSF and rituximab. Antibiotics, antimycotics and antivirals were given orally. Results: Thirteen patients with MS were prospectively accrued in the study. There were 7 females and 6 males. Median age was 48 years, range 24 to 65. The expanded disability status scale (EDSS) score of these patients had a median of 5 points (range 1 to 6). All the autografts were started on an outpatient basis and two persons were admitted to the hospital during the procedure (persistent nausea/vomiting and neutropenic fever); they stayed in the hospital for 48 hours. In order to obtain a minimum of 1 x106 viable CD34+ cells/Kg, one to four apheresis were done (median 1). The total number of viable CD34+ cells infused to the patients ranged between 1 and 9.6x106 (median 3.1). Patients recovered above 0.5 x109/L absolute granulocytes on median day 9 (range 6 to 12). No individuals needed transfusions of red blood cells nor platelets transfusions. There were no transplant-related deaths and the 23-month overall survival of the autografted patients is 100%. Median cost of the procedure was 30 000 USD. In 8 persons the EDSS was assessed three months after the graft; it diminished from a median of 4.5 to a median of 2.5. In 5 patients, the three months re-assessment of the EDSS has not been possible as a result of the time elapsed after the autograft. Discussion: These data indicate that it is possible to conduct autotrasplants for patients with MS employing a simplification of the conventional procedures by means of non-frozen peripheral blood stem cells and outpatient conduction. Additional information is needed to asses the efficacy of these procedures in the treatment of patients with MS. Disclosures No relevant conflicts of interest to declare.

A Feasibility Study of the Full Outpatient Conduction of Hematopoietic Transplants in Persons with Multiple Sclerosis Employing Autologous Non-Cryopreserved Peripheral Blood Stem Cells

2017 ◽  
Vol 137 (4) ◽  
pp. 214-219 ◽  
Author(s):  
Guillermo J. Ruiz-Argüelles ◽  
Andrés A. León-Peña ◽  
Mónica León-González ◽  
Ana Karen Nuñez-Cortes ◽  
Juan Carlos Olivares-Gazca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Peripheral Blood ◽  
Outpatient Basis ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Additional Information ◽  
Cd34 Cells ◽  
Relapsing Remitting ◽  
Blood Stem Cells

Background: With the goal of achieving immune system reset, autologous hematopoietic stem cell transplantations have been performed in patients with multiple sclerosis (MS). Material and Methods: Two hundred and eighty-six consecutive patients with MS were autografted in a single center using non-frozen peripheral blood stem cells (PBSCs), on an outpatient basis and conditioning with cyclophosphamide and rituximab. The protocol was registered in ClinicalTrials.gov identifier NCT02674217. Results: One hundred and ninety-four females and 92 males were included; the median age was 47. All procedures were started on an outpatient basis and only 8 persons needed to be admitted to the hospital during the procedure. In order to obtain at least 1 × 106/kg viable CD34 cells, 1-4 aphereses were performed (median 1). The total number of viable CD34+ cells infused ranged between 1 and 19.2 × 106/kg (median 4.6). Patients recovered above 0.5 × 109/L absolute granulocytes on median day 8 (range 0-12). Two individuals needed red blood cells but none needed platelet transfusions. There were no transplant-related deaths and the 128-month overall survival of the patients is 100%. In 82 persons followed up for 3 or more months, the Expanded Disability Status Scale diminished from a mean of 5.2-4.9, the best results being obtained in relapsing-remitting and primary progressive MS. Conclusions: It is possible to conduct autotransplants for patients with MS employing non-frozen PBSCs and outpatient conduction. Additional information is needed to assess the efficacy of these procedures in the treatment of patients with MS.

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.

scholarly journals Transplantation of allogeneic CD34+ peripheral blood stem cells in patients with advanced hematologic malignancy

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4132-4138 ◽  
Author(s):  
WI Bensinger ◽  
CD Buckner ◽  
K Shannon-Dorcy ◽  
S Rowley ◽  
FR Appelbaum ◽  
...  
Keyword(s):  
Stem Cells ◽  
Body Weight ◽  
Peripheral Blood ◽  
Hematologic Malignancy ◽  
Chronic Gvhd ◽  
Allogeneic Transplantation ◽  
Hematologic Malignancies ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Sixteen patients with advanced hematologic malignancies were transplanted with HLA-identical allogeneic peripheral blood stem cells (PBSCs) that were selected for CD34+ cells by an avidin-biotin immunoadsorption technique. The median age of patients was 48 years (range, 37 to 67). Patients received 12.0 or 13.2 Gy of total body irradiation followed by 120 mg/kg of cyclophosphamide. Normal donors received 16 mg/kg of granulocyte-colony stimulating factor on days 1 to 6 followed by PBSC harvests on days 4 to 7. PBSC harvests were processed each day on a single avidin-blotin column containing an antibody to the CD34 antigen and processed cells were infused without cryopreservation daily for 4 consecutive days. Prophylaxis against graft-versus-host disease (GVHD) consisted of cyclosporine alone for 5 patients and CSA plus methotrexate for 11 patients. A median of 18.64 (6.74 to 34.97) x 10(8) CD34+ cells/kg patient body weight were collected from each donor. A median of 8.96 (2.62 to 17.34) x 10(8) CD34+ cells/kg patient body weight were recovered after avidin-biotin adsorption which represented a median CD34+ cell yield of 53% (18% to 77%) with a median purity of 62% (34% to 82%). There was a reduction in CD3+ cells from a median of 557.26 (227.73 to 677.77) x 106/kg to 0.73 x 10(4)/kg (0.40 to 3.65), in CD4+ cells from 351.72 (194.47 to 520.11) x 10(6)/kg to 0.40 (0.15 to 1.03) x 10(4)/kg and in CD8+ cells from 169.74 (53.34 to 325.83) x 10(6)/ kg to 0.32 (0.12 to 2.71) x 10(4)/kg representing a median 2.8 (2.19 to 3.14) log reduction in T cells. One patient died of infection on day 3 posttransplant and was unevaluable for recovery of neutrophils. The median day to recovery of 500 neutrophils/mL was 15 (8 to 26) in the remaining 15 patients. Six of 16 patients falled to achieve a platelet count of 20,000/mL before death on days 3 to 97 of transplant-related complications. The median day to achieving platelets of 20,000 mL in the remaining 10 patients was 11 (7 to 31). Eight of 16 patients (50%) died between 3 and 97 days posttransplant, 7 of transplant-related causes, and 1 of progressive disease. Grade 2–4 acute GVHD occurred in 12 out of 14 (86%) and grades 3–4 in 6 out of 14 (43%) evaluable patients. Six of 8 evaluable patients developed clinical chronic GVHD and 1 developed subclinical chronic GVHD. Bone marrow and/or peripheral blood chimerism studies in 12 evaluable patients showed 97% to 100% donor type in 11 patients with 1 patient in relapse showing 40% donor cells 60 to 90 days posttransplant. Four of 16 patients (25%) are alive and disease-free 312 to 576 days after transplant. There were no episodes of graft failure or rejection. This study shows that allogeneic transplantation using CD34+ selected PBSC results in prompt and sustained engraftment. CD34+ selection, as employed in this preliminary study, however, resulted in an apparently higher rate of acute and chronic GVHD. However, The sample size is quite small and precludes a more definitive conclusion regarding GVHD.

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.

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