CD34+ Selection before Autologous Peripheral Blood Stem Cell Transplantation: Comparison of the Nexell Isolex 300i® and Miltenyi Biotec CliniMACS® Systems.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1070-1070
Author(s):  
Simon Mantha ◽  
David G. Savage ◽  
Gwen L. Nichols ◽  
Donna Skerrett ◽  
Charles S. Hesdorffer
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Plasma Cell Dyscrasia ◽  
P Value ◽  
Student’S T ◽  
Cd34 Selection ◽  
Number Of Cells ◽  
Student’S T Test

Abstract Autologous stem cell transplant has been used with variable success rates in the treatment of different malignancies. One of the potential causes of relapse is contamination of the stem cell collection by neoplastic cells. Purging the stem cells by CD34+ selection has been used to reduce such contamination. In this study two different devices were compared in their efficiency to achieve CD34+ selection of peripheral blood stem cells collected in individuals undergoing autologous transplant for breast cancer, neuroblastoma, plasma cell dyscrasia, lymphoma (both Hodgkin and non Hodgkin), rhabdomyosarcoma and amyloidosis. A total of 28 patients were randomized to CD34 selection on the Nexell Isolex 300i® system (NIS) or the Miltenyi Biotec CliniMACS® (MCMS) system. The prevalence of plasma cell dyscrasia was higher in the MCMS group (57%) than in the NIS group (22%). On the other hand, there were 2 cases of Hodgkin lymphoma and 2 cases of breast cancer in the NIS group, in comparison to none in the MCMS group. Average values for parameters of selection efficacy for the 19 patients transplanted are shown in table 1 (recovery = number of cells post / number of cells pre-selection X 100, viability measured with the trypan blue exclusion test). Transplant was done as per local protocols according to the type of malignancy. CD34+ cell dose was determined by institutional guidelines. Average values for engraftment are shown in table 2 (two patients who died before engraftment in the MCMS group were excluded from calculation of the mean values). One patient died of graft failure in the MCMS group in contrast to none in the NIS group. Although the numbers of patients are relatively low, this is the first randomized study in which the selection efficiency of the NIS and MCMS devices have been compared in patients receiving CD34-selected autografts. CFU-GM recovery and cell viability were lower, while neutrophil engraftment was slower in the MCMS group, but these differences were not statistically significant. Our data do not show any clinically significant advantage for either the NIS or MCMS selection device. Table 1 Device CD34+ recovery (%,range) CFU-GEMM recovery (%,range) CFU-GM recovery (%,range) Viability pre (%,range) Viability post (%,range) P-value calculated with Student’s t-Test. NIS 52 (16–76) 5 (1–14) 9 (0–42) 95 (91–99) 95 (90–99) MCMS 66 (48–75) 4 (1–5) 5 (0–9) 94 (80–99) 88 (60–100) P 0.17 0.71 0.57 0.69 0.16 Table 2 Device CD34+ infused (X 106/kg, range) Time to ANC ≥500 (days, range) Time to plt ≥20 (days, range) # Units plt P-value calculated with Student’s t-Test. NIS 3.6 (2.0–5.2) 12.2 (9–20) 15.9 (11–38) 19.4 (0–30) MCMS 3.6 (1.5–5.1) 15.1 (11- ∞) 16.8 (9-∞) 40.2 (6–150) P - 0.22 0.79 0.23

Engraftment and molecular monitoring of CD34+ peripheral-blood stem-cell transplants for follicular lymphoma: a pilot study.

1997 ◽  
Vol 15 (6) ◽  
pp. 2288-2295 ◽  
Author(s):  
I G McQuaker ◽  
A P Haynes ◽  
S Anderson ◽  
C Stainer ◽  
R G Owen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pilot Study ◽  
Follicular Lymphoma ◽  
Peripheral Blood ◽  
Blood Stem Cell ◽  
High Dose ◽  
Nested Polymerase Chain Reaction ◽  
Cd34 Selection

PURPOSE A pilot study to validate the use of CD34+ selection (Ceprate SC) of blood stem-cell collection in patients with advanced follicular lymphoma receiving myeloablative chemoradiotherapy. PATIENTS AND METHODS Seventeen patients were entered onto the protocol. Thirteen of 17 patients have undergone transplantation; the median age is 42.5 years (range, 33 to 51), seven of 13 are stage IVB, two stage IVA, three stage IIIB, and one stage IIB. All except two patients were treated after first or subsequent relapses after receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy to achieve a good partial (six of 13) or complete (seven of 13) response before stem-cell mobilization with cyclophosphamide 3 g/m2 and filgrastim 300 microg once daily. RESULTS Eleven of 13 patients had a detectable t(14;18) by nested polymerase chain reaction (PCR). Median CD34+ count before selection was 2.9 x 10(6)/kg (range, 1.17 to 11.3) and after CD34+ selection was 1.54 x 10(6)/kg (range, 0.88 to 7.6) with a median CD34+ yield of 62.4% (range, 17% to 95%) and purity of 60% (range, 39.3% to 73%). Of the 11 patients known to have t(14;18), 10 had PCR-detectable contamination of stem-cell harvests that became PCR negative in six of the 10 after CD34+ selection. Engraftment was rapid with a median day to absolute neutrophil count (ANC) greater than 0.5 x 10(9)/L of 13 days (range, 11 to 21) and platelet count greater than 20 x 10(9)/L of 14 days (range, 10 to 44). With a median follow-up duration of 15 months, three patients have remained persistently PCR-positive, two of whom received PCR-positive stem cells. Two have relapsed. Of the seven patients who received PCR-negative stem cells, five have had no PCR-detectable disease in posttransplant bone marrow samples. CONCLUSION Longer follow-up duration is required to determine the significance of these findings, but we have confirmed the feasibility of CD34+ selected cells to deplete peripheral-blood stem cells of tumor cells from patients undergoing high-dose therapy for follicular lymphoma.

scholarly journals ID:3003 Increase in CD34 cells in peripheral blood following HLA randomized, ABO-matched cord blood transfusion in patients with advanced malignancy and anemia: Prognostic implications

2017 ◽  
Vol 4 (S) ◽  
pp. 13
Author(s):  
Niranjan Bhattacharya
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Blood Transfusion ◽  
Cord Blood ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
P Value ◽  
Advanced Cancer Patients ◽  
Advanced Malignancy ◽  
Cd34 Cells

Cord blood is a safe alternative of adult blood for transfusion given its content of fetal and adult haemoglobin,  platelet and WBC counts, and a plasma filled with inflammatory and non-inflammatory cytokines and growth factors. It also has a hypoantigenic nature and altered metabolic profile and is rich in haematopoietic stem cells (CD34) . It has potential for treatment of anemia in diseases of different aetiologies including malignancy.  ​ STUDY DESIGN: In the present study, 46 sex and HLA-randomized patients suffering from advanced malignancy  and anemia (Hb 8 Gm percent or less) were treated with   placental cord blood transfusion.  CD34 cells were collected from peripheral blood 72 hours after transfusion and variations were analyzed for prognostic implication. The study period was between 16 August 1999 and 16 May 2006. ​ RESULTS AND ANALYSIS: Among the forty-six cases included in this study , Case no  2 (breast sarcoma) received the lowest amount of card blood (6 units), while Case no 46 (breast cancer) received the largest amount (32 units). The youngest patient, suffering from non-Hodgkin's lymphoma (Case 3), was a 16-year-old boy who received eight units of cord blood to combat anemia. Other patients received amounts varying from 7-15 units: Case 14 received 15 units (metachronous lymph node metastatsis), Case 19 received 14 units (breast cancer), and Case 25 received seven units (lung cancer). ​ There was no transfusion-related visible immunological or nonimmunological reaction in any patient. Studies of CD34 levels after 72 hours of transfusion showed an initial rise followed by a fall in twenty-two cases, two cases registered very little effect on the CD34 level, i.e., no change from the baseline, and the rest of the cases demonstrated a sustained rise from the baseline, i.e, 56% to 99% of peripheral mononuclear cells and a sustained high CD34 level. ​ CONCLUSION: This preliminary study indicates that freshly collected cord blood transfusion may cause a transient transplant impact of transfused cord blood CD34 stem cells on the host without provoking clinical graft vs host disease perhaps due to a possible background structural or functional  immune suppression in advanced malignancy. From the cord blood transfusion impact we could clinically divide the enrolled advanced cancer patients to a relatively  good (Group A)  and bad prognostic(Group B) variety of  cancer. The survival rate of patients where we detected a persistant rise of CD34 in peripheral blood after 3 units or more of transfusion of HLA randomized ABO matched and screened cord blood  was over 3 years and the cases where there are no rise of peripheral blood CD34 level in spite of repeated transfusion of 5- 32 units of cord blood died within 3 months or earlier (p value less than .01)

High-activity samarium-153-EDTMP therapy followed by autologous peripheral blood stem cell support in unresectable osteosarcoma

2001 ◽  
Vol 40 (06) ◽  
pp. 215-220 ◽  
Author(s):  
S. Bielack ◽  
S. Flege ◽  
J. Eckardt ◽  
J. Sciuk ◽  
H. Jürgens ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
High Activity ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Blood Stem Cell ◽  
High Dose ◽  
External Radiotherapy ◽  
Primary Tumor Site ◽  
Hematopoietic Stem

Summary Purpose: Despite highly efficacious chemotherapy, patients with osteosarcomas still have a poor prognosis if adequate surgical control cannot be obtained. These patients may benefit from therapy with radiolabeled phosphonates. Patients and Methods: Six patients (three male, three female; seven to 41 years) with unresectable primary osteosarcoma (n = 3) or unresectable recurrent sites of osteosarcomas (n = 3) were treated with high-activity of Sm-153-EDTMP (150 MBq/kg BW). In all patients autologous peripheral blood stem cells had been collected before Sm-153-EDTMP therapy. Results: No immediate adverse reactions were observed in the patients. In one patient bone pain increased during the first 48 hrs after therapy. Three patients received pain relief. Autologous peripheral blood stem cell reinfusion was performed on day +12 to +27 in all patients to overcome potentially irreversible damage to the hematopoietic stem cells. In three patient external radiotherapy of the primary tumor site was performed after Sm-153-EDTMP therapy and in two of them polychemotherapy was continued. Thirty-six months later one of these patients is still free of progression. Two further patients are still alive. However, they have developed new metastases. The three patients who had no accompanying external radiotherapy, all died of disease progression five to 20 months after therapy. Conclusion: These preliminary results show that high-dose Sm-153-EDTMP therapy is feasible and warrants further evaluation of efficacy. The combination with external radiation and polychemotherapy seems to be most promising. Although osteosarcoma is believed to be relatively radioresistant, the total focal dose achieved may delay local progression or even achieve permanent local tumor control in patients with surgically inaccessible primary or relapsing tumors.

Efficient lentiviral gene transfer to canine repopulating cells using an overnight transduction protocol

Blood ◽  
2004 ◽  
Vol 103 (10) ◽  
pp. 3710-3716 ◽  
Author(s):  
Peter A. Horn ◽  
Kirsten A. Keyser ◽  
Laura J. Peterson ◽  
Tobias Neff ◽  
Bobbie M. Thomasson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Gene Transfer ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Lentiviral Vectors ◽  
Large Animal ◽  
Hematopoietic Stem ◽  
Lentiviral Transduction ◽  
Mobilized Peripheral Blood

Abstract The use of lentiviral vectors for the transduction of hematopoietic stem cells has evoked much interest owing to their ability to stably integrate into the genome of nondividing cells. However, published large animal studies have reported highly variable gene transfer rates of typically less than 1%. Here we report the use of lentiviral vectors for the transduction of canine CD34+ hematopoietic repopulating cells using a very short, 18-hour transduction protocol. We compared lentiviral transduction of hematopoietic repopulating cells from either stem cell factor (SCF)– and granulocyte-colony stimulating factor (G-CSF)–primed marrow or mobilized peripheral blood in a competitive repopulation assay in 3 dogs. All dogs engrafted rapidly within 9 days. Transgene expression was detected in all lineages (B cells, T cells, granulocytes, and red blood cells as well as platelets) indicating multilineage engraftment of transduced cells, with overall long-term marking levels of up to 12%. Gene transfer levels in mobilized peripheral blood cells were slightly higher than in primed marrow cells. In conclusion, we show efficient lentiviral transduction of canine repopulating cells using an overnight transduction protocol. These results have important implications for the design of stem cell gene therapy protocols, especially for those diseases in which the maintenance of stem cells in culture is a major limitation.

Abstract 239: Stem Cell Therapy Improves Critical Limb Ischemia

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Alaa Marzouk
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Embryonic Stem ◽  
Limb Ischemia ◽  
Control Group ◽  
Chronic Limb Ischemia

Introduction: The journey from single cell to complex being is attributable to stem cells role. Adult stem cells originate during ontogeny & persist in specialized niches within organs. Asymmetric division of each stem cell during differentiation produces : one daughter stem cell & one daughter transit amplifying/intermediate cell having migratory properties. Forced migration of hematopoietic stem/progenitor cells (HSPC) from bone marrow into peripheral blood is called mobilization. Accumulating evidence suggests that attenuation of the chemokine stromal derived factor-1(SDF-1)-CXCR4 axis that plays a pivotal role in retention of HSPC in bone marrow (BM) results in the release of these cells from the BM into peripheral blood. Recently, adult cells have been genetically reprogrammed to an embryonic stem cell like state. Induced pluripotent stem cells (IPSCs) were similar to human embryonic stem cells in morphology, proliferative capacity, expression of cell surface antigens, & gene expression. Treatment of ischemic vascular disease of lower limbs remains a significant challenge. Unfortunately, if medical & surgical salvage procedures fail, amputation is an unavoidable result for those patients. Aim of Work: (Hypothesis) To assess the application of implantation of autologous stem/progenitor cell in the treatment of chronic limb ischemia & to evaluate the safety, efficacy & feasibility of this novel therapeutic approach. Methods: A total of 24 patients with chronic limb ischemia not eligible for arterial reconstruction or endovascular procedures were enrolled & randomized (1:1) to either the implanted group or the control group. Control group: Conventional medical therapy in the form of anti platelet therapy & vasodilators. Implanted group: Subcutaneous injection of 300μ g/day of recombinant human granulocyte colony stimulating factor (G-CSF) for 5 days to mobilize stem/progenitor cells from BM. Total leucocytic count is measured daily to follow up successful mobilization of bone marrow mononuclear cells (BMMNCs). Stem cell Harvesting After 5 days peripheral blood mononuclear cells (PBMNCs) were harvested using a cell separator. Samples from apheresis products are subjected to TLC measurement & immunophenotypic characterization of CD34+ cells by flow cytometry. The collected PBMNCs were implanted by multiple intramuscular injections into ischemic limbs. Results: There was significant increase in pain free walking distance & ankle/brachial index (ABI) & significant decreased rest pain. Effectiveness was documented by : reduced number of amputation, increase ABI & improvement of the quality of life in therapeutic group compared to control group. Conclusion: The novel therapeutic approach of PBMNCs implantation in patients with chronic limb ischemia is safe, feasible & effective in decreasing co-morbidity & rate of amputation. Safety was manifested by absence of complications during G-CSF therapy or during harvesting & injection of the stem cells. Recommendations: 1- Future studies on larger number of patients & longer follow up. 2- Controlled studies using different methods & different cell population (PBMNCs, BMMNCs or MSCs) to compare the outcome of each. 3-Studing the role of endothelial progenitor cell dysfunction in different ischemic diseases to develop successful gene therapy.

scholarly journals Effect of ondansetron on spinal induced hypotension in caesarean deliveries

2020 ◽  
Vol 8 (4) ◽  
pp. 193-199
Author(s):  
Pujan Balla ◽  
Anil Shrestha ◽  
Ninadini Shrestha ◽  
Navindra Bista ◽  
Moda Nath Marhatta
Keyword(s):  
Spinal Anesthesia ◽  
Elective Caesarean Section ◽  
P Value ◽  
Chi Square ◽  
Induced Hypotension ◽  
Intergroup Comparison ◽  
Chi Square Test ◽  
The Mean ◽  
Student’S T ◽  
Student’S T Test

Background: Spinal anesthesia is the preferred technique of anesthesia employed for caesarean sections. However, it is very often complicated by hypotension. Different drugs and techniques have been used to prevent the hypotension induced by spinal anesthesia. In this study, the effect of ondansetron on the prevention of hypotension after spinal anesthesia was evaluated. Objectives: To determine the effect of prophylactic ondansetron on prevention of spinal induced hypotension in elective caesarean section. Methodology: Eighty-six parturients planned for elective caesarean deliveries were randomized into two groups of 43 each. Group O received Ondansetron 4 mg (4 ml) and Group S received Normal Saline (4 ml) intravenously 10 minutes prior to spinal anesthesia. Blood pressure, heart rate, phenylephrine requirements, occurrence of nausea and vomiting and APGAR scores of neonates were compared between the groups. Hemodynamic data was analyzed using Student’s t-test for intergroup comparison and ANOVA was used for intragroup comparison. Categorical data was analyzed using Pearson Chi-Square test. For all determinants, p-value <0.05 was considered significant. Results: Occurrence of hypotension in Group O (20.9 %) was significantly lower than in Group S (72.1%) (p < 0.05). The mean arterial pressure was significantly higher in Group O at 2, 6, 8, 12 and 14 minutes (p < 0.05). The use of phenylephrine (37.21 mcg vs. 146.51 mcg, p < 0.05) and occurrence of nausea (11.6%, vs. 41.9% p < 0.002) was significantly lower in ondansetron group. Conclusion: Ondansetron is effective in preventing spinal induced hypotension in elective caesarean sections.

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