Higher Efficacy of Peripheral Blood Stem Cell Collection in Children Mobilized with High-Dose G-CSF.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5274-5274
Author(s):  
Jan Styczynski ◽  
Robert Debski ◽  
Hanna Gornicka ◽  
Elzbieta Hulek ◽  
Pawel Wojtylak ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Count ◽  
Peripheral Blood ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Peripheral Blood Cd34 ◽  
Group I ◽  
Cd34 Cells ◽  
Stem Cell Collection ◽  
Number Of Cells

Abstract Objective: Analysis of efficacy of PBSC collection after mobilization by high-dose G-CSF in children and young adults, qualified for transplantation of autologous hematopoietic stem cells. Patients and Methods: Total number of 21 patients (23 collection cycles) were included into the study, divided into 2 groups: group I of 10 patients (aged 16m-23y, weight 8.5–61kg) with solid tumors were mobilized with G-CSF (Neupogen) at dose 2x5 μg/kg bw/day (12 collection cycles); group II of 11 patients (aged 3–27y, weight 12.5–68kg) with solid tumors (n=6) or hematological malignancies (n=5), who were mobilized with G-CSF (Neupogen) at dose 2x12 μg/kg bw/day. PBSC collections were performed by COBE Spectra from the day when CD34 cell count exceeded 20/μl. Efficacy of procedure was determined by collection of total 2x106 CD34 cells/kg (minimal required cell dose), or 5x106 CD34 cells/kg (optimal cell dose). Results: Group I: Peripheral blood CD34 cell count exceeded 20/μl in 7/12 (58%) patients at day 4 and 10/12 (83%) at day 6 of G-CSF administration. Total number of CD34 cells of 2x106 /kg kw and 5x106 /kg bw was obtained in 3/12 (25%) and 2/12 (17%) patients after first collection respectively; and in 8/12 (67%) and 4/12 (33%) after second collection, respectively. After 3 days of collection required number of cells was obtained in 9/12 (75%) and 6/12 (50%) patients, respectively. No patient reported side-effects related to G-CSF administration. Group II: Peripheral blood CD34 cell count exceeded 20/μl in 8/11 (73%) patients at day 4 and 11/11 at day 6 of G-CSF administration. Total number of CD34 cells of 2x106 /kg bw and 5x106 /kg bw was obtained in 9/11 (82%) and 3/11 (27%) patients after first collection respectively; and in 11/11 and 6/11 (55%) after second collection, respectively. After 3 days of collection, in all patients, but one, optimal number of cells was obtained. Two patients reported side-effects related to G-CSF administration (headache, bone pain). No differences were found between the rate of speed of PBSC mobilization in analyzed schemes of G-CSF administration, however group of patients mobilized with high-dose G-CSF, showed more efficient stem cell collection after 3 days of procedure (p=0.027; OR=14; 95%CI=1.1–402). Conclusion: Mobilization of PBSC with high-dose G-CSF is a safe and effective method of hematopoietic stem cell collection, enabling high efficacy of this procedure.

Phase I Study of Intravenous Plerixafor Added to a Mobilization Regimen of G-CSF In Lymphoma Patients Undergoing Autologous Stem Cell Collection

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 823-823 ◽  
Author(s):  
Amanda Cashen ◽  
Michael P. Rettig ◽  
Feng Gao ◽  
Camille N. Abboud ◽  
Keith E. Stockerl-Goldstein ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Surface ◽  
Phase I ◽  
Cell Count ◽  
Peripheral Blood ◽  
Peripheral Blood Cd34 ◽  
Human Cd34 ◽  
Cd34 Cells ◽  
Stem Cell Collection ◽  
Subset Distribution

Abstract Abstract 823 Background: Plerixafor, a reversible inhibitor of the interaction between stromal cell-derived factor 1 (SDF-1) and CXCR4, improves autologous stem cell collection in patients with non-Hodgkin lymphoma (NHL), multiple myeloma, and Hodgkin lymphoma (HL). In Phase II and III trials, plerixafor has been combined with the standard G-CSF regimen and administered as a subcutaneous (sc) injection of 0.24 mg/kg, given 9–11 hours before pheresis. Intravenous (IV) administration of plerixafor may result in a faster rise and higher peak in the peripheral CD34+ cell count, allowing administration of plerixafor the same day as pheresis and improving stem cell collection. Methods: The primary objectives of this Phase I/II study were to determine the maximum tolerated dose (MTD) of IV plerixafor, up to 0.40 mg/kg combined with G-CSF, and to determine the efficacy of IV plerixafor + G-CSF to mobilize ≥ 2 × 106 CD34+ cells/kg from patients with lymphoma. Patients were given an initial dose of plerixafor 0.24 mg/kg sc on day -5, to assess the mobilization of CD34+ cell subsets, and then started mobilization with G-CSF (10 ug/kg SC daily) on days -4 thru -1 and on each day of pheresis. IV plerixafor was given over 30 min. 4 hrs. before each pheresis, beginning day 0. Samples for CD34+ cell subsets were collected after treatment with plerixafor only on day -5, after 5 days of G-CSF on day 0 (G-CSF only), and 4 hrs after plerixafor administration on day 0 (G-CSF + plerixafor). Human CD34+ cells were purified by positive selection with a Magnetic Affinity Cell Selection CD34 isolation kit. Results: In the Phase I component of the study, 25 adult pts. (median age 49) with NHL (n=15) or HL (n=10) were treated with IV plerixafor at escalating doses (10 pts. at 0.16 mg/kg, 3 at 0.24 mg/kg, 6 at 0.32 mg/kg, and 6 at 0.40 mg/kg). One dose-limiting toxicity (grade 2 chest pain) was observed at 0.32 mg/kg, and no grade 3/4 toxicities occurred at 0.40 mg/kg. 24 of 25 pts. (96%) met the goal collection of ≥ 2.0 × 106 CD34+ cells/kg. 21 of 25 pts. (84%) collected ≥ 5.0 × 106 CD34+ cells/kg in a median 1 day of pheresis, including 6 of 6 pts. in the 400 ug/kg cohort. Peripheral blood CD34+ cell count increased median 27-fold (range, 4–174) after G-CSF + plerixafor IV and 2.1-fold (range, 0.8–7.0) 4 hours after the first dose of IV plerixafor. There was a positive correlation between peripheral blood CD34+ cell count 6 hr. after plerixafor SC on day -5 and both peripheral blood CD34+ cell count after G-CSF mobilization and first day stem cell collection. Human CD34+ hematopoietic stem and progenitor cells (HSPCs) were divided into four distinct subsets based on their cell surface expression of CD45RA and CD123 (IL-3Rα): (1) CD34+CD45RA-CD123+/− primitive HSPCs, (2) CD34+CD45RA+CD123+/− committed progenitors, (3) CD34dimCD45RA+CD123hi plasmacytoid dendritic cell (pDC) progenitors and (4) CD34+CD45RA-CD123hi cells of unknown function. Table 1 shows the CD34+ cell subset distribution following sequential mobilization with plerixafor, G-CSF, and plerixafor + G-CSF (PL+G). G-CSF mobilized grafts were enriched with CD45RA-CD123+/− primitive HSPCs while plerixafor preferentially mobilized the CD34dimCD45RA+CD123hi pDC precursors and CD34+CD45RA-CD123hi cells. We found no significant differences in the CD34+ subset distribution between HL and NHL pts. Flow cytometric analyses showed that the CD34+ subsets preferentially mobilized by plerixafor expressed high levels of cell surface CXCR4. Conclusion: Plerixafor IV, at doses up to 0.40 mg/kg, is well-tolerated and effective when added to G-CSF for the mobilization of stem cells from patients with lymphoma, with mobilization kinetics and stem cell collections that compare favorably with sc dosing. The Phase II study is proceeding at the 0.40 mg/kg dose. In addition, our data suggest that G-CSF and plerixafor mobilize distinct subsets of human CD34+ HSPCs. The impact of these cells on the engraftment and function of plerixafor mobilized grafts requires further study. Disclosures: Rettig: Genzyme Corp.: Consultancy, Honoraria. Vij:Genzyme: Honoraria, Speakers Bureau. Uy:Genzyme: Consultancy, Honoraria, Research Funding.

scholarly journals Factors affecting autologous peripheral blood hematopoietic stem cell collections by large-volume leukapheresis: a single center experience

2011 ◽  
Vol 9 (2) ◽  
pp. 196-200 ◽  
Author(s):  
Araci Massami Sakashita ◽  
Andrea Tiemi Kondo ◽  
Andreza Alice Feitosa Ribeiro ◽  
Andrea Neri Folchini Cipolletta ◽  
Monica Vilela Colesanti ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Count ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Cell Yield ◽  
Hematopoietic Stem ◽  
Factors Affecting ◽  
Peripheral Blood Cd34 ◽  
Stem Cell Collection

Objective: To evaluate factors affecting peripheral blood hematopoietic stem cell yield in patients undergoing large-volume leukapheresis for autologous peripheral blood stem cell collection. Methods: Data from 304 consecutive autologous peripheral blood stem cell donors mobilized with hematopoietic growth factor (usually G-CSF), associated or not with chemotherapy, at Hospital Israelita Albert Einstein between February 1999 and June 2010 were retrospectively analyzed. The objective was to obtain at least 2 × 106 CD34+ cells/kg of body weight. Pre-mobilization factors analyzed included patient's age, gender and diagnosis. Post mobilization parameters evaluated were pre-apheresis peripheral white blood cell count, immature circulating cell count, mononuclear cell count, peripheral blood CD34+ cell count, platelet count, and hemoglobin level. The effect of pre and post-mobilization factors on hematopoietic stem cell collection yield was investigated using logistic regression analysis (univariate and multivariate approaches). Results: Pre-mobilization factors correlating to poor CD34 + cell yield in univariate analysis were acute myeloid leukemia (p = 0.017) and other hematological diseases (p = 0.023). Significant post-mobilization factors included peripheral blood immature circulating cells (p = 0.001), granulocytes (p = 0.002), hemoglobin level (p = 0.016), and CD34+ cell concentration (p < 0.001) in the first harvesting day. However, according to multivariate analysis, peripheral blood CD34+ cell content (p < 0.001) was the only independent factor that significantly correlated to poor hematopoietic stem cell yield. Conclusion: In this study, peripheral blood CD34+ cell concentration was the only factor significantly correlated to yield in patients submitted to for autologous collection.

scholarly journals Lower Hematopoietic Progenitor Cell Counts and Yields at Subsequent Donations Is Influenced By a Shorter Inter-Donation Interval between the First and Subsequent Mobilizations

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1962-1962
Author(s):  
Sandhya R. Panch ◽  
Brent R. Logan ◽  
Jennifer A. Sees ◽  
Bipin N. Savani ◽  
Nirali N. Shah ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Peripheral Blood ◽  
Research Funding ◽  
Time Interval ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Peripheral Blood Cd34 ◽  
Cell Counts ◽  
Cd34 Cells

Introduction: Approximately 7% of unrelated hematopoietic stem cell (HSC) donors are asked to donate a subsequent time to the same or different recipient. In a recent large CIBMTR study of second time donors, Stroncek et al. incidentally found that second peripheral blood stem cell (PBSC) collections had lower total CD34+ cells, CD34+ cells per liter of whole blood processed, and CD34+ cells per kg donor weight. Based on smaller studies, the time between the two independent PBSC donations (inter-donation interval) as well as donor sex, race and baseline lymphocyte counts appear to influence CD34+ cell yields at subsequent donations. Our objective was to retrospectively evaluate factors contributory to CD34+ cell yields at subsequent PBSC donation amongst NMDP donors. Methods. The study population consisted of filgrastim (G-CSF) mobilized PBSC donors through the NMDP/CIBMTR between 2006 and 2017, with a subsequent donation of the same product. evaluated the impact of inter-donation interval, donor demographics (age, BMI, race, sex, G-CSF dose, year of procedure, need for central line) and changes in complete blood counts (CBC), on the CD34+ cell yields/liter (x106/L) of blood processed at second donation and pre-apheresis (Day 5) peripheral blood CD34+ cell counts/liter (x106/L) at second donation. Linear regression was used to model log cell yields as a function of donor and collection related variables, time between donations, and changes in baseline values from first to second donation. Stepwise model building, along with interactions among significant variables were assessed. The Pearson chi-square test or the Kruskal-Wallis test compared discrete variables or continuous variables, respectively. For multivariate analysis, a significance level of 0.01 was used due to the large number of variables considered. Results: Among 513 PBSC donors who subsequently donated a second PBSC product, clinically relevant decreases in values at the second donation were observed in pre-apheresis CD34+ cells (73.9 vs. 68.6; p=0.03), CD34+cells/L blood processed (32.2 vs. 30.1; p=0.06), and total final CD34+ cell count (x106) (608 vs. 556; p=0.02). Median time interval between first and second PBSC donations was 11.7 months (range: 0.3-128.1). Using the median pre-apheresis peripheral blood CD34+ cell counts from donation 1 as the cut-off for high versus low mobilizers, we found that individuals who were likely to be high or low mobilizers at first donation were also likely to be high or low mobilizers at second donation, respectively (Table 1). This was independent of the inter-donation interval. In multivariate analyses, those with an inter-donation interval of >12 months, demonstrated higher CD34+cells/L blood processed compared to donors donating within a year (mean ratio 1.15, p<0.0001). Change in donor BMI was also a predictor for PBSC yields. If donor BMI decreased at second donation, so did the CD34+cells/L blood processed (0.74, p <0.0001). An average G-CSF dose above 960mcg was also associated with an increase in CD34+cells/L blood processed compared to donors who received less than 960mcg (1.04, p=0.005). (Table 2A). Pre-apheresis peripheral blood CD34+ cells on Day 5 of second donation were also affected by the inter-donation interval, with higher cell counts associated with a longer time interval (>12 months) between donations (1.23, p<0.0001). Further, independent of the inter-donation interval, GCSF doses greater than 960mcg per day associated with higher pre-apheresis CD34+ cells at second donation (1.26, p<0.0001); as was a higher baseline WBC count (>6.9) (1.3, p<0.0001) (Table 2B). Conclusions: In this large retrospective study of second time unrelated PBSC donors, a longer inter-donation interval was confirmed to be associated with better PBSC mobilization and collection. Given hematopoietic stem cell cycling times of 9-12 months in humans, where possible, repeat donors may be chosen based on these intervals to optimize PBSC yields. Changes in BMI are also to be considered while recruiting repeat donors. Some of these parameters may be improved marginally by increasing G-CSF dose within permissible limits. In most instances, however, sub-optimal mobilizers at first donation appear to donate suboptimal numbers of HSC at their subsequent donation. Disclosures Pulsipher: CSL Behring: Membership on an entity's Board of Directors or advisory committees; Miltenyi: Research Funding; Bellicum: Consultancy; Amgen: Other: Lecture; Jazz: Other: Education for employees; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Medac: Honoraria. Shaw:Therakos: Other: Speaker Engagement.

Peripheral Blood Stem Cell Harvests Performed Beyond the Initial Two Days of Apheresis May Not Contribute to Accelerate Granulocyte and Platelet Engraftment After Autologous Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3226-3226
Author(s):  
Luciano Wannesson ◽  
Lisa Wang ◽  
John Kuruvilla ◽  
Tracy Nagy ◽  
Ronnie Saragosa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Peripheral Blood ◽  
High Dose ◽  
Platelet Recovery ◽  
Neutrophil Recovery ◽  
Cell Dose ◽  
Group I ◽  
Cd34 Cells

Abstract Abstract 3226 Poster Board III-163 Introduction Measurement of the number of CD34+ cells in the leukapheresis product is universally used as a surrogate measure of the capacity of peripheral blood stem cells (PBSC) to reconstitute hematopoiesis. Early studies demonstrated that engraftment times are shorter and predictable if at least 5 ×106 CD34+ cells/kg are administered following high-dose chemotherapy. However, satisfactory neutrophil and platelet recovery occurs after infusions of >2.0 ×106 CD34+ cells/kg. Previous analyses demonstrated the presence of different subsets of CD34+ cells in the peripheral blood at different times during mobilization, with pluripotent subsets arising and decreasing earlier after mobilization and more committed subsets peaking later [Stewart et al, Exp Hematol 1995; 23: 1619-27]. We hypothesized that for equivalent CD34+ cell dose, there could be a difference in engraftment kinetics according to the number of days of apheresis required to obtain an adequate PBSC graft. Patients and Methods Data from 270 consecutive autografts performed between July 1999 and April 2006 for non-Hodgkin and Hodgkin lymphoma (58% and 25%, respectively), breast cancer (8%), germ-cell tumors (2%) and acute myeloid leukemia (7%) were analyzed. Mobilization was performed using cyclophosphamide +/- etoposide + G-CSF 10μg/kg; patients received G-CSF after PBSC infusion from day 10 until neutrophil recovery >1500/μL. Patients were stratified in 3 groups according to the SC dose administered as follows: Low-dose (L) <2 ×106 CD34+ cells/kg, Intermediate-dose (I) 2 to 5 ×106 CD34+ cells/kg and High-dose (H) >5 ×106 CD34+ cells/kg and in 2 categories according to the number of days of apheresis performed (≤2 and 3+). The data analysis was divided in 3 steps. Step 1: we made a comparison of engraftment results for group L vs. I and I vs. H. Step 2: to explore potential engraftment differences within each cell dose stratum according to the number of days of apheresis required, that is, I(≤2) vs. I(3+) and H(≤2) vs. H(3+). Step 3: to test the influence of performing additional harvests beyond day 2 on engraftment kinetics we compared group I(≤2) vs. group H(3+), i.e. those who obtained the optimal number of CD34+ cells through additional collections during the same mobilization. Differences between groups were estimated by the Mann-Whitney test and by Cox regression model. Results The step 1 analysis confirmed that engraftment was faster for the H group (N=138, median 11 days for ANC>500/μl and N=132, median 11 days for unsupported platelet count >20000/μl) than for the I group (N=118, median 11 days and N=98, 12 days for neutrophils and platelets, respectively) and the L group (N=14, median 12 days and N=12, median 15 days for neutrophils and platelets, respectively). Two-sided p-values favored I in L vs. I (p=0.0185 for neutrophils and p=0.0013 for platelets) and favored H in I vs. H (p=0.0002 for neutrophils and p=0.019 for platelets). The step 2 analysis did not show any statistical difference in engraftment times within groups L, I and H, according to the number of apheresis (≤2 vs. 3+), but there was a trend for faster platelet engraftment for patients in the ≤2 group (p=0.08). There was no difference between the ≤2 and 3+ subgroups in terms of age and number of chemotherapy lines received before transplant; although, in the ≤2 group there were more patients with breast cancer (10.3% vs. 4.8%) and Hodgkin lymphoma (32.2% vs. 16.1%) and fewer pts with non-Hodgkin lymphoma (66.1% vs. 48%) compared to the 3+ group (p<0.001). Step 3 analysis showed no difference for neutrophil recovery between subgroups I≤2 and H3+ (N=28, median 11 days for I≤2 and N=20, median 10 days for H3+, p=0.08) and platelet engraftment (median 11 days for I≤2 and 12 days for H3+, p=0.54). Even dough, patients in the I≤2 cohort received significantly less CD34+ cells/kg (median 4.46, range 2.10-4.99) compared to those in the H3+ group (median 6.33, range 5.10-8.99, p<0.001) and were similar in terms of age and number of lines of prior therapy. Conclusions Provided more than 2 ×106 CD34+ cells/kg are obtained in two days of leukapheresis, optimal engraftment times can be achieved even if the threshold of 5 ×106 CD34+ cells/kg is not reached. Our results suggest that the addition of harvest days beyond 2 days to obtain ≥5 ×106 CD34+ cells/kg may not contribute to improved short-term engraftment kinetics. Disclosures No relevant conflicts of interest to declare.

High Dose Plerixafor Is Safe and Mobilizes Higher Numbers of CD34+ Cells Compared with Standard Dose Plerixafor

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 585-585
Author(s):  
Jeremy M Pantin ◽  
Xin Tian ◽  
Matthew M. Hsieh ◽  
Lisa Cook ◽  
Theresa Donohue ◽  
...  
Keyword(s):  
Stem Cell ◽  
Single Dose ◽  
Adverse Events ◽  
Dose Level ◽  
Peripheral Blood ◽  
Standard Dose ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Cell Numbers ◽  
Cd34 Cells

Abstract Abstract 585 Introduction Plerixafor is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 (SDF-1) to its cognate receptor CXCR4. This results in therapid release of CD34+ cells into circulation, which can then be collected by apheresis. Plerixafor is FDA approved at the 240 μg/kg dose to be used in conjunction with G-CSF to mobilize autografts for transplantation. Allogeneic grafts can also be mobilized using single agent plerixafor without G-CSF, and following transplantation, result in sustained donor derived hematopoiesis. However, when the 240 μg/kg dose is used, 1/3 of donors fail to mobilize minimally acceptable doses of CD34+ cells. Recently, we demonstrated the safety of administration of a single dose of 480 μg/kg of subcutaneous (sc) plerixafor in humans. We subsequently conducted a randomized cross-over trial comparing CD34+ mobilization in healthy subjects mobilized with a single dose of sc plerixafor given at either a high dose (480 μg/kg) or a conventional dose (240 μg/kg). Methods Twenty normal healthy volunteers were randomized and received either a 240 or 480 μg/kg dose of sc plerixafor followed by at least a 2 week wash out period then were administered the other dose of plerixafor. Circulating numbers of leukocytes and CD34+ cells/μlwere measured at multiple time points for 24 hours following each plerixafor injection and the CD34+ AUC over 24 hours was calculated for each subject at each dose level. Peripheral blood colony forming unit (CFU) assays were performed at baseline and 6 hours after plerixafor dosing. Adverse events were graded using CTCAE version 3.A sample size of 20 subjects was determined to have over 90% power to detect an absolute CD34+ count difference of 10/μl using this crossover design and a two-sidedpaired t-test at the 0.05 level. Results Twenty-three subjects were enrolled and 20 completed administration of both doses. Peak circulating CD34+ cell numbers (median 31.5 vs 25, p=0.0009), circulating CD34+ cell numbers at 24hrs (median 15.5 vs 9, p<0.0001), and the CD34+ AUC over 24 hours (median 543 vs 411, p<0.0001) were all significantly higher following the administration of the 480 μg/kg plerixafor dose compared to the 240 μg/kg dose. The time to peak CD34+ was also slightly longer after the 480 μg/kg dose (median 10 vs 8 hrs, p=0.011). These differences were not related to the order of administration of the 2 different plerixafor doses. Although GM-CFUs from the peripheral blood at 6hrs following plerixafor were significantly higher compared to baseline levels at both plerixafordoses, there was no dose-effect relationship observed between drug dose and fold increase in GM-CFUs. The incidence and severity of AE's did not differ between lower and higher doses of plerixafor and no grade 3 or greater adverse events occurred at either dose level. Conclusion These preliminary data suggest high dose plerixafor can be administered safely and may mobilize more CD34+ cells than standard dose plerixafor. Furthermore, these data suggest mobilization following a single dose of plerixafor and a single apheresis procedure would result in graft collections containing higher CD34+ cell numbers when allogeneic stem cell donors are mobilized with high-dose plerixafor compared to standard-dose. Disclosures: Off Label Use: Plerixafor, a hematopoietic stem cell mobilizer, is indicated in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM).

A Pilot Study of Peripheral Blood Hematopoietic Stem Cells Mobilization with the Combination of Bortezomib and G-CSF in Multiple Myeloma and Non-Hodgkin's Lymphoma Patients.

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1902-1902
Author(s):  
Divaya Bhutani ◽  
Vidya sri Kondadasula ◽  
Joseph P. Uberti ◽  
Voravit Ratanatharathorn ◽  
Lawrence G. Lum ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Median Number ◽  
Peripheral Blood Cd34 ◽  
Cd34 Cells ◽  
Group A ◽  
Cell Mobilization ◽  
Group B ◽  
Stem Cell Collection

Abstract Background: Bortezomib has become an integral part of front-line therapy of multiple myeloma in a large majority of patients. There are preliminary reports which show that addition of bortezomib can augment the peripheral blood CD34 count during stem cell mobilization. In this single center prospective trial we added bortezomib to G-CSF to evaluate the effects of bortezomib on peripheral CD34 counts and collection. Methods: Patients aged 18-70 years with diagnosis of multiple myeloma (MM) or non-hodgkin's lymphoma (NHL) who were eligible for autologous stem cell transplantation (ASCT) and had received no more than three prior chemotherapeutic regimens were eligible for the study. Patients were enrolled in two groups. Group A (N=3) received G-CSF 16mcg/kg for 5 days and proceeded to stem cell collection on D5 and then received bortezomib 1.3mg/m2 on D5 after stem cell collection and G-CSF 16mcg/kg on D6, 7, 8 and repeat stem cell collection on D6, 7, 8 till the goal was achieved. Group B (N=17) received G-CSF 16mg/kg on D1-5 and received bortezomib 1.3mg/m2 on D4 and proceeded to stem cell collection on D5. If the patient was not able to collect the predefined goal CD34, G-CSF was continued on D 6, 7, 8 and a second dose of bortezomib 1.3mg/m2 was given on D7. Mobilization procedure was stopped once the predefined goal CD34 collection (4 x 106/kg for MM and 2 x 106/kg for NHL) had been collected. Primary objectives of the study was to determine if addition of bortezomib to G-CSF will result in an increase in PBSCs by > 2-fold and to achieve median neutrophil engraftment 12 days post ASCT. Secondary objectiveswere to evaluate the collected product for co-mobilization of lymphoma or myeloma cells and to determine if the use of bortezomib increases the mobilization of immune-stimulatory Dendritic cell (DC) -1 subsets. Results: A total of 23 patients were enrolled and 20 were evaluable for the results. Only one patient with NHL was enrolled and rest had MM. Median age of pts was 57 years, M/F 8/12, median number of previous chemotherapy regimens was 1 (range 1-3). The median peripheral blood CD34 count pre and post bortezomib in all patients were 28.8 x 106/kg and 37 x 106/kg respectively. All three patients in group A had drop in peripheral blood CD34 counts on D6 post bortezomib as they had undergone stem cell collection on day 5. In part B (N=17), 15 patients had increase in peripheral blood CD 34+ve cell counts with 4 patients achieved doubling while 11 pts had less than doubling of peripheral blood CD34 count after receiving bortezomib. Two patients had minimal drop in the peripheral blood CD34 counts post bortezomib. Median number of CD34 cells collected in15 patients (part B) were 5.06 x 106 CD34 cells/kg (range 4-15.1). 18 patients proceeded to ASCT and median time to neutrophil engraftment (ANC ≥500/cumm) post transplant was 12 days (range 11-16) and platelet engraftment (Plt count ≥ 20,000/cumm) was 18 days (range 15-27). There was no significant change in DC1/DC2 ratio in both groups following treatment with bortezomib and G-CSF (Figure 1). In group A all three patients collected goal CD34 count on day 5 and 2/3 patients collected >4 x106 CD34 cells/kg on D6 post bortezomib and1/3 patients collected 2.6 x 106 on D6 post bortezomib. In group B (n=17), 2 patients were unable to collect because of low CD34 counts on D4 and D5, 11 pts collected the goal in one day (D 5) and 4 pts required two days of apheresis (D 5 and 6). None of the patients received D7 bortezomib. Conclusion: Use of bortezomib during autologous stem cell collection was safe and well tolerated. Majority of patients had increase in peripheral blood CD34 counts post bortezomib administration on D4. Future trials should explore bortezomib as an alternate strategy to chemo-mobilization in combination with growth factors. Figure 1. DC1/DC2 ratio in group A and group B at various time points. Figure 1. DC1/DC2 ratio in group A and group B at various time points. Figure 2. Figure 2. Disclosures Off Label Use: Bortezomib for stem cell mobilization. Lum:Karyopharm Therapeutics Inc: Equity Ownership; Transtarget.Inc: Equity Ownership. Deol:Bristol meyer squibb: Research Funding. Abidi:celgene: Speakers Bureau; Millenium: Research Funding.

scholarly journals Absolute numbers of peripheral blood CD34+ hematopoietic stem cells prior to a leukapheresis procedure as a parameter predicting the efficiency of stem cell collection

2017 ◽  
Vol 89 (7) ◽  
pp. 18-24 ◽  
Author(s):  
I V Galtseva ◽  
Yu O Davydova ◽  
T V Gaponova ◽  
N M Kapranov ◽  
L A Kuzmina ◽  
...  
Keyword(s):  
Stem Cells ◽  
Body Weight ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Close Correlation ◽  
Blood Leukocytes ◽  
Hematopoietic Stem ◽  
Peripheral Blood Cd34 ◽  
Cd34 Cells ◽  
Stem Cell Collection

Aim. To identify a parameter predicting a collection of at least 2·106 CD34+ hematopoietic stem cells (HSC)/kg body weight per leukapheresis (LA) procedure. Subjects and methods. The investigation included 189 patients with hematological malignancies and 3 HSC donors, who underwent mobilization of stem cells with their subsequent collection by LA. Absolute numbers of peripheral blood leukocytes and CD34+ cells before a LA procedure, as well as a number of CD34+ cells/kg body weight (BW) in the LA product stored on the same day were determined in each patient (donor). Results. There was no correlation between the number of leukocytes and that of stored CD34+ cells/kg BW. There was a close correlation between the count of peripheral blood CD34+ cells prior to LA and that of collected CD34+ cells calculated with reference to kg BW. Conclusion. The optimal absolute blood CD34+ cell count was estimated to 20 per µl, at which a LA procedure makes it possible to collect 2·106 or more CD34+ cells/kg BW.

scholarly journals G-CSF Plus Preemptive Plerixafor Versus Cyclophosphamide Plus G-CSF for Autologous Stem Cell Mobilization in Multiple Myeloma: Effectiveness, Safety and Cost Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5823-5823
Author(s):  
Ahmad Antar ◽  
Zaher Otrock ◽  
Mohamed Kharfan-Dabaja ◽  
Hussein Abou Ghaddara ◽  
Nabila Kreidieh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Stem Cell Mobilization ◽  
Cell Yield ◽  
Fixed Dose ◽  
High Dose ◽  
Peripheral Blood Cd34 ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Introduction: The optimal stem cell mobilization regimen for patients with multiple myeloma (MM) remains undefined. Most transplant centers use either a chemo-mobilization strategy using cyclophosphamide (CY) and granulocyte-colony stimulating factor (G-CSF) or a steady state strategy using G-CSF alone or with plerixafor in case of mobilization failure. However, very few studies compared efficacy, toxicity and cost-effectiveness of stem cell mobilization with cyclophosphamide (CY) and G-CSF versus G-CSF with preemptive plerixafor. In this study, we retrospectively compared our single center experience at the American University of Beirut in 89 MM patients using fractionated high-dose CY and G-CSF as our past preferred chemo-mobilization strategy in MM patients with our new mobilization strategy using G-CSF plus preemptive plerixafor. The change in practice was implemented when plerixafor became available, in order to avoid CY associated toxicity. Patients and methods: Patients in the CY group (n=62) (Table 1) received either fractionated high-dose CY (n=56) (5g/m2 divided in 5 doses of 1g/m2 every 3 hours) or CY at 50mg/kg/day for 2 doses (n=6). G-CSF was started on day +6 of chemotherapy at a fixed dose of 300 µg subcutaneously every 12 hours. All patients in the plerixafor group (n=27) (Table 1) received G-CSF at a fixed dose of 300 µg subcutaneously every 12 hours daily for 4 days. On day 5, if peripheral blood CD34+ was ≥ 20/µl, apheresis was started immediately. Plerixafor (240 µg/kg) was given 7-11 hours before the first apheresis if CD34+ cell count on peripheral blood on day 5 was <20/µl and before the second apheresis if CD34+ cells on the first collect were <3х106/kg. The median number of prior therapies was 1 (range: 1-3) in both groups. Results: Compared with plerixafor, CY use was associated with higher median peak peripheral blood CD34+ counts (35 vs 111 cells/µl, P= 0.000003), and total CD34+ cell yield (7.5 х 106 vs 15.9 х 106 cells/kg, P= 0.003). All patients in both groups collected ≥4x106 CD34+ cells/Kg. Moreover, 60 (96.7%) and 46 (74.2%) patients in the CY group vs 24 (88.8%) and 6 (22%) patients in the plerixafor group collected >6х106 and >10x106 CD34+ cells/kg, respectively (P=0.16; P<0.00001). Only 4 (6.4%) patients required two apheresis sessions in the CY group compared to 11 (40%) in the plerixafor group (P=0.0001). Conversely, CY use was associated with higher frequency of febrile neutropenia (60% vs 0%; P<0.00001), blood transfusions (27% vs 0%; P<0.00001), platelets transfusion (25% vs 0%; P<0.00001) and hospitalizations (64% vs 0%; P<0.00001). No one required intensive level of care and all recovered. Autografting was successfully performed in all patients using high-dose melphalan with a median time from mobilization to the first transplant of 31 days (range: 16-156) in the CY group compared to 13 days (range: 8-40) in the plerixafor group (P=0.027); and median infused CD34+ cells were 7х106/kg (range: 3.1-15.3) versus 5.27 (2.6-7.45), respectively (P=0.002). The average total cost of mobilization using the adjusted costs based on National Social Security Fund (NSSF) prices in Lebanon in the plerixafor group was slightly higher compared with the CY group ($7964 vs $7536; P=0.16). Conclusions: Our data indicate robust stem cell mobilization in MM patients with either fractionated high-dose CY and G-CSF or G-CSF alone with preemptive plerixafor. The chemo-mobilization approach was associated with two-fold stem cell yield, slightly lower cost (including cost of hospitalization) but significantly increased toxicity. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Ex vivo expansion and maturation of peripheral blood CD34+ cells into the myeloid lineage

Blood ◽  
1992 ◽  
Vol 80 (6) ◽  
pp. 1405-1412 ◽  
Author(s):  
DN Haylock ◽  
LB To ◽  
TL Dowse ◽  
CA Juttner ◽  
PJ Simmons
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Fold Increase ◽  
Hematopoietic Stem ◽  
Cell Production ◽  
Peripheral Blood Cd34 ◽  
Cd34 Cells

Abstract Hematopoietic reconstitution (HR) after peripheral blood stem cell transplantation is characterized by a delay of 8 and 12 days for recovery to safe levels of neutrophils and platelets even in patients with the most rapid engraftment. We postulate that a further enhancement in the rate of HR may be achieved by transplanting with an expanded postprogenitor cell population that can provide mature functional cells within days of infusion. In this study we investigated the ability of combinations of hematopoietic growth factors (HGF) to generate nascent granulocyte-macrophage colony-forming units (CFU-GM) in a 7-day suspension culture of peripheral blood CD34+ cells. A combination of 6 HGF, ie, interleukin-1 beta (IL-1), IL-3, IL-6, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage- CSF (GM-CSF), and stem cell factor (SCF), was identified as the most potent combination of those tested. Subsequently, large volume suspension cultures of CD34+ cells from the same patients using the same 6-factor combination were established and monitored for 21 days. An exponential rate of nucleated cell production (mean 1,324-fold increase) occurred during culture. CFU-GM production paralleled nucleated cell production until day 10, peaked at day 14 (mean 66-fold increase), and was then maintained until day 21. Cells produced in culture were predominantly neutrophil precursors and developed normally as assessed by morphology, immunophenotype, and superoxide generation. This stroma-free, cytokine-driven culture system can achieve a degree of amplification, which suggests the feasibility of ex vivo culture of hematopoietic progenitor cells as an adjunct to hematopoietic stem cell transplantation.

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