Poor Mobilizers in an Autologous Hematopoietic Stem Cell Transplantation Setting: Matched Pair Analysis Profiling G-CSF and Plerixafor-Mobilized Stem Cells

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4413-4413
Author(s):  
Line Nederby ◽  
Lea Bjerre Hokland ◽  
Katrine Nielsen ◽  
Erik Kay Segel ◽  
Peter Hokland ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Matched Pair ◽  
Aldh Activity ◽  
Cd34 Cells ◽  
Poor Mobilizers

Abstract Abstract 4413 Granulocyte colony-stimulating factor (G-CSF; Neupogen) is by far the most commonly used agent for mobilization of stem cells for autologous peripheral blood stem cell transplantation (ASCT) of non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), and multiple myeloma (MM) patients. However, up to 30% of the patients will fail to mobilize the targeted amount of CD34+ cells. The addition of plerixafor has been shown to mobilize the stem cells when G-CSF fails to do so. However, no reports have hitherto addressed and compared the biology of the CD34+ stem cells obtained from an inadequate G-CSF mobilization and a subsequent plerixafor administration. Given these considerations, this study was aimed at assessing the proportion of stem cells by means of phenotype and colony-forming potential. Given that CD34 is at best only a surrogate marker for stemness, we here included the aldehyde dehydrogenase (ALDH) activity, an emerging crucial marker in stem cell biology, to evaluate the stem cell pool in paired samples obtained after G-CSF and plerixafor administration. Cryopreserved samples of peripheral blood mononuclear cells (PBMC) from patients diagnosed with NHL (n=3), MM (n=4), and HL (n=1,) were directly compared. All patients were heavily treated with at least 3 cytoreductive regimens prior to the decision to proceed with ASCT. Different mobilizing regimens were applied, but all received one dose of plerixafor (0.24mg/kg sc) as a result of failed G-CSF mobilization (12mg/kg sc twice daily for 3–5 days). The PBMCs were obtained from the morning CD34+ screening sample taken 1) during G-CSF mobilization, typically 1–2- days before it was substituted with plerixafor, and 2) the morning after the plerixafor injection. The percentages of CD34+CD38+ and CD34+CD38- cells and the percentage of ALDHbright CD34+ cells in the samples of the suboptimal G-CSF mobilization and the matched plerixafor/G-CSF mobilization were analyzed and calculated as percentage of PBMC. These samples were also subjected to semisolid culturing and colonies were quantified after 14 days, where CFU-GEMM, BFU-E, and CFU-GM were enumerated. We found no significant difference in the percentage of CD34+CD38+ and CD34+CD38- cells in the cell pools recovered from G-CSF (mean 0.68%, SD 0.281 and mean 0.183%, SD 0.095, respectively) and plerixafor mobilization (mean 1.123%, SD 1.143 and mean 0.361%, SD 0.316, respectively) (n=8, Wilcoxon matched-pairs signed rank test, p=0.46 and p=0.15, respectively). Importantly, when comparing the percentage of ALDHbright CD34+ cells (G-CSF: mean 0.071%, SD 0.048. Plerixafor: mean 0.261%, SD 0.298) in the same matching samples the difference between them was not significant (p=0.11). Finally, the numbers of CFU-GEMM (G-CSF: mean 12.13, SD 16.65. Plerixafor: mean 12.5, SD 14.23), BFU-E (G-CSF: mean 2.375, SD 3.926. Plerixafor: mean 4.125, SD 7.06), and CFU-C colonies (G-CSF: mean 9, SD 13.68. Plerixafor: mean 10.5, SD 11.45) originating from the matching G-CSF and plerixafor-mobilized cells were not significantly different (p=0.93, p=0.29, p=1, respectively). Collectively, these data reveal that in poor G-CSF mobilizers, the ratios of CD34+CD38+ and CD34+CD38- cells to PBMCs were equal in the matching samples recovered from G-CSF and plerixafor mobilization clearly suggesting that successful plerixafor mobilization is the consequence of increased cell release only in otherwise poor mobilizers. Notably, plerixafor and G-CSF caused the release of stem cells with equal degrees of stemness and commitment as measured by ALDH activity, percentages of CD34+ cells, and colony forming potential. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Beginning of a Journey of Autologous Stem Cell Transplantation in Combined Military Hospital, Dhaka, Bangladesh

2018 ◽  
Vol 8 (2) ◽  
pp. 177-180
Author(s):  
Mohammed Mosleh Uddin ◽  
Huque Mahfuz ◽  
Md Mostafil Karim
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Haematopoietic Stem Cell ◽  
Military Hospital

Haematopoietic stem cell transplantation (HSCT) involves the intravenous infusion of autologous or allogenic stem cells collected from bone marrow, peripheral blood or umbilical cord to re-establish haematopoietic function in patients whose bone marrow or immune system is damaged or defective. HSCT are mainly of two types –autologous stem cell transplantation (SCT) and allogenic SCT. Autologous SCT is mainly performed in multiple myeloma, Hodgkin lymphoma, non-Hodgkin lymphoma and less commonly in acute myeloid leukaemia. Haematopoietic stem cells are mobilized from bone marrow to the peripheral blood after the use of mobilizing agents, granulocyte colony stimulating factor (G-CSF) and plerixafor. Then the mobilized stem cells are collected from peripheral blood by apheresis and cryo-preserved. The patient is prepared by giving conditioning regimen (high dose melphelan). Stem cells, which are already collected, are re-infused into patient’s circulation by a blood transfusion set. Engraftment happens 7-14 days after auto SCT. Common side effects of this procedure include nausea, vomiting, diarrhoea, mucositis, infections etc. The first case of SCT performed in Combined Military Hospital, Dhaka, Bangladesh is presented here.Birdem Med J 2018; 8(2): 177-180

Subsets of CD34+ and Engraftment Kinetics in Allogeneic Peripheral Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2954-2954
Author(s):  
Domenico Pastore ◽  
Anna Mestice ◽  
Paola Carluccio ◽  
Tommasina Perrone ◽  
Manuela Leo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Conditioning Regimen ◽  
The Other ◽  
Peripheral Blood Stem Cells ◽  
Gvhd Prophylaxis ◽  
Cd34 Cells

Abstract Engraftment kinetics in allogeneic peripheral blood stem cell transplantation (alloPBSCT) depend on the number and efficiency of the stem cells in the graft, the conditioning regimen and GvHD prophylaxis. Currently, stem cell evaluation is performed by counting CD34+ cells; however, CD34+ cells are a heterogeneous population including the early uncommitted fraction as well as different subsets committed to one or the other lineage; hence, defining the CD34+ subset most predictive of engraftment and its threshold value would be of the utmost importance. This study aimed to identify which graft product subset of CD34+ cells might be the most predictive of early hematopoietic recovery following alloPBSCT. The relationships between the number of “mature” subsets of CD34+ cells (CD34+/CD33+, CD34+/CD38+, CD34+/DR+ and CD34+/CD133) and “immature” subsets of CD34+ cells (CD34+/CD33−, CD34+/CD38−, CD34+/DR− and CD34+/CD133+) and early neutrophil and platelet engraftment were studied in a homogeneous series (for disease, pre-transplant chemotherapy, conditioning regimen GvHD prophylaxis) of 30 acute myeloid leukemia (AML) patients after alloPBSCT from HLA-identical siblings. All patients received the BU-CY regimen consisting of busulfan 4 mg/kg/day for 4 consecutive days followed by cyclophosphamide 60 mg/kg/day for 2 consecutive days; GvHD prophylaxis included cyclosporin and methotrexate. The CD34+ dose infused ranged from 2.9 to 8.8 × 106/Kg (median 4.6); the percentage of immature CD34+ cells was 36% for CD34+/CD33−, 60% for CD34+/CD38−, 5% for CD34+/DR− and 70% for CD34+/CD133+; this translates into a median dose of 1.6 × 106/Kg (range 0.3–5) for CD34+/CD33−, 2.6 × 106/Kg (range 0.1–6.2) for CD34+/CD38−, 0.4 × 106/Kg (range 0.1–2.3) for CD34+/DR− and 0.95 ×106/Kg (range 0.6–2.3) × 106/Kg for CD34+/CD133+. Median time to achieve engraftment of neutrophils and platelets was 13 days (range 10–16) and 15 days (range 13–19), respectively. In our experience the total CD34+/CD133+ cell number was inversely correlated with the days required for recovery of 0.5 × 109/L neutrophils (r = −0.76, p<0.05) and 100 × 109/L platelets (r = −0.71, p<0.05); this correlation was better than the total CD34+ cells dose and neutrophil (r = −0.71, p<0.05) and platelets engraftment (r = −0.68, p = 0.06). No correlation was found between the other CD34+ subsets and neutrophil and platelets engraftment. With regard to the threshold dose for early neutrophil engraftment, all 14 patients who received more than 1 × 106/Kg of CD34+/CD133+ had a neutrophil count higher than 1.0 × 109/L at 12 days. We suggest that a high number of CD34+/CD133+ peripheral blood stem cells may be associated with faster neutrophils and platelets recovery; these findings may help to predict the repopulating capacity of PBSC in patients after allogeneic PBSCT, especially when a relatively low number of CD34+ cells is infused.

Abstract 32: Intravenous Mobilized Autologous Peripheral Blood CD34+ Stem Cell Transplantation for Angina

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Hadyanto Lim ◽  
Lindarto Dharma ◽  
Zein Umar ◽  
Hariaji Ilham
Keyword(s):  
Stem Cell ◽  
Angina Pectoris ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Exercise Tolerance ◽  
Exercise Stress ◽  
Peripheral Blood Cd34 ◽  
Cd34 Cells ◽  
Angina Frequency

Background: Intramyocardial CD34+ stem cell therapy for patients with refractory angina shows that this is safe and feasible. We aimed to determine whether intravenous transplantation of mobilized autologous peripheral blood CD34+ stem cells provides beneficial effects for patients with angina pectoris. Methods: We administered granulocyte colony stimulating factor (G-CSF, 5.0 μg/kg/day) subcutaneously once a day for 4 days to 15 patients (4 women and 11 men aged 50-78 years) with intractable angina pectoris (Canadian Cardiovascular Society functional class III-IV) for mobilization of CD34+ cells into the peripheral blood. Ischemia was assessed by exercise stress testing. Leukapheresis procedure was started on the day 4 of G-CSF using the Spectra Optia cell separator. Circulating and intravenous transplantation of autologous CD34+ cells after leukapheresis were measured by flow cytometry. The effects of G-CSF on blood were measured by hematology analyzer and semi-auto chemistry analyzer. Results: Intravenous peripheral blood CD34+ cells increased after leukapheresis (from 1.12±0.48 cells/μL to 107.42±23.83 cells/μL, p<0.001) and total white blood cells count (from 7.82 ± 2.63x10 3 /μl to 37.47±15.07 x10 3 /μl, p<0.001). Indices of hsCRP, platelets, hemoglobin, alanine aminotransferase, lactic dehydrogenase, and uric acid were not changed by treatment. At week 4, angina frequency was significantly lower after intravenous CD34+ cells (from 15.07±4.03 to 3.27±1.49, p<0.001). Similarly, improvement in exercise tolerance was significantly higher by stem cell transplantation (from 5.90±2.53 minutes to 8.41±2.49 minutes, p<0.001). Most patients reported mild myalgia which were easily managed with acetaminophen. Conclusions: Intravenous autologous CD34+ stem cell transplantation improved angina frequency and exercise tolerance. The cell mobilization and leukapheresis procedures were found safe and tolerable in patients with angina pectoris.

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.

Ex-Vivo Expanded Peripheral Blood Stem Cells (EVEC) Compared with Un Manipulated Peripheral Blood Stem Cells (PBSC) Autologous Transplantation for Multiple Myeloma: A Pair Match Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 502-502 ◽  
Author(s):  
Noel-Jean Milpied ◽  
Gerald Marit ◽  
Bernard Dazey ◽  
Jean-Michel Boiron ◽  
Zoran Ivanovic ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Abstract 502 Autologous stem cell transplantation with PBSC after high-dose chemotherapy remains standard therapy for patients with symptomatic Multiple Myeloma (MM). Strategies to minimize complications could significantly reduce the morbidity of that procedure. One possibility could be to shorten the duration of induced neutropenia through the injection of an ex-vivo expanded graft. Nineteen patients (pts) received EVEC after high-dose Melphalan (HDM) (200 mg/m2) as the only graft. The ex-vivo expanded procedure has been described elsewhere (Boiron et al. Transfusion 2006 and Ivanovic et al. Transfusion 2006). Briefly, thawed peripheral blood CD 34+ cells collected after G-CSF mobilisation and selected with immunomagnetic devices were incubated for 10 days in a serum free medium (Maco Biotech HP01) with Stem Cell Factor (Amgen), G-CSF (Amgen) and TPO (Amgen: 7 pts; Cellgenix:12 pts). The expanded cells were then thoroughly washed and injected 48h after the HDM injection. The ex-vivo expansion lead to a median fold of 5,4 for CD34+ cells (1,3-11,8); 118 for CD33+ (1-703880); 3386 for CD14+ (4-101075); 28,5 for CD13+ (10-703880) and 13 for CFUs (6-21). The median N° of CD34+ cells injected was 14×10e6/kg (5,3-48). The results of these transplants were compared to those achieved in 38 pts who received unmanipulated PBSC after HDM. Pts and controls were matched for age, sex, stage of the disease, first line chemotherapy ( VAD or VD) status of the disease at time of transplant, year of transplant, time between diagnosis and transplant, CD34+ mobilisation technique (HD cytoxan + G-CSF or G-CSF alone) and the median N° of total nucleated cells and of CD34+ collected. The results are summarized on the table: There was no secondary neutropenia in the patients who received EVEC. With a median FU of the entire cohort of 30 m, the median OS for pts who received their first transplant with EVEC and with PBSC is 69 m and not reached respectively (p=NS), the median PFS is 18 m and 27 m (p = NS) and the median time to progression is 14 m and 15 m (p=NS). Conclusion: EVEC is feasible, safe and reduce significantly the morbidity of autologous stem cell transplantation after HDM for multiple myeloma. Disclosures: Milpied: Amgen France: Honoraria.

Effectiveness and Potential Strategies to Improve Outcomes Following Chemomobilization with Etoposide + G-CSF in Patients Undergoing Autologous Stem Cell Transplantation for Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2083-2083
Author(s):  
William A Wood ◽  
Julia Whitley ◽  
Ravi K Goyal ◽  
Paul M Brown ◽  
Andrew Sharf ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Cost Effective ◽  
Phase Iii ◽  
Published Data ◽  
Peripheral Blood Cd34 ◽  
Poor Mobilizers

Abstract Abstract 2083 INTRODUCTION: The addition of chemotherapy to G-CSF for stem cell mobilization prior to autologous stem cell transplantation (ASCT) provides the potential for increased cell yield and improved mobilization outcomes relative to G-CSF alone. We have investigated the use of mid-dose VP-16 plus G-CSF in pts with lymphoma and examined whether plerixafor might be incorporated into this chemomobilization backbone in a cost-effective way for a population with inferior outcomes. METHODS: Between June 2004 and September 2010, 159 pts with lymphoma underwent ASCT following the use of VP-16 (375mg/m2 on D#1 and D#2) and G-CSF (5mcg/kg twice daily from D#3 through the final day of collection) for mobilization. 26 pts also received a dose of Rituximab (375mg/m2) on D#1. Stem cell collection was initiated when the peripheral blood CD34 cell count was more than 7 per ul. Data on costs for fixed and variable expenditures associated with mobilization and collection were calculated on an individual patient basis. Costs also included unexpected complications such as inpatient hospitalizations, antibiotic use and blood product transfusions. “Poor mobilizers” were defined as pts failing to collect 5 × 106 cells in one or two days. Univariable and multivariate logistic regression were performed to identify predictive models for poor mobilization and to identify hypothetical breakpoint scenarios for the cost-effective utilization of plerixafor. For the breakpoint scenarios, a median of 3 doses of plerixafor was assumed based on the published phase III data with plerixafor plus G-CSF. RESULTS: Of 159 pts with lymphoma, 90 (57%) were identified as “good mobilizers,” 43% were “poor mobilizers”, and 150 (94%) collected at least 2 × 10 6th/kg CD34 cells in total (83% within 4 apheresis sessions), comparing favorably to published data with G-CSF alone or G-CSF + plerixafor. 51 (32%) required PRBC or platelet transfusion, 10 (6%) were admitted to the hospital during the mobilization period, and 8(5%) required a second mobilization or bone marrow harvest. There was no increased incidence of secondary malignancies. Average costs were $14923 ($6121-$24546) for good mobilizers and $27044 ($12206-$51846) for poor mobilizers (p<0.05). The first peripheral blood CD34 count (obtained between D9-D15, with 82% of first counts obtained on D12), accurately predicted “good” vs “poor” mobilizers (c statistic 0.941, CD34 cutpoint 27/uL). Using our data, we estimated that it would not be cost effective to give plerixafor to all patients, even if 100% of patients subsequently became “good” mobilizers (net loss $15,817/pt). Instead, by reserving plerixafor for only predicted “poor” mobilizers (probability<0.5) at the time of first CD34 count, we estimated that 64% (n=49) of predicted “poor” mobilizers would need to become “good” mobilizers in order to achieve cost neutrality. CONCLUSION: VP-16 and G-CSF is a safe and effective mobilization regimen for pts with lymphoma and compares favorably to published data with G-CSF alone or G-CSF + plerixafor. Mobilization outcomes after chemomobilization might be further improved in a cost-effective way by adding plerixafor in patients predicted by the first peripheral blood CD34 count to be poor mobilizers. This will be investigated prospectively. Disclosures: Shea: Otsuka Pharmaceuticals: Research Funding.

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