Analysis of Donor Demographic and Laboratory Parameters Affecting CD34+ Cell Mobilization In Healthy Allogeneic Pediatric Peripheral Blood Stem Cell (PBSC) Donors

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2259-2259 ◽  
Author(s):  
Cedar J Fowler ◽  
Yu Ying Yau ◽  
Charles D. Bolan ◽  
Susan Leitman
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Total Dose ◽  
Mononuclear Cell ◽  
Peripheral Blood ◽  
Donor Age ◽  
Cell Counts ◽  
Younger Age ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 2259 Background: In healthy adult donors undergoing blood stem cell mobilization, we previously showed that the single strongest factor related to peak pre-apheresis circulating CD34+ cell counts was the total dose of granulocyte colony-stimulating factor (G-CSF) administered to the donor. Donor weight and gender were also highly correlated with peak CD34+ cell mobilization, to the degree that they contributed to the total dose of G-CSF administered. To determine if this relationship applied to younger donors, we analyzed the factors affecting PBSC mobilization in healthy allogeneic pediatric subjects. Methods: A retrospective analysis of 44 consecutive allogeneic PBSC collections performed between 1998 and 2009 in healthy pediatric donors in a single institution was done. Pediatric subjects were defined as less than 18 years old and less than 60 kg. Mobilization was with G-CSF (filgrastim) alone, given subcutaneously as 10 mcg/kg once daily (n=42), or 8 mcg/kg BID (n=2), for 5 consecutive days. Leukapheresis was initiated on day 5, at least 2 hours after the final G-CSF dose, using either the CS3000 (Fenwal) or Spectra (Gambro) cell separator. Central venous access was necessary in 29 of 44 subjects (66%). Donor demographics, self-reported ethnic backgrounds, and peripheral blood and component CD34+ cell counts were assessed at each procedure. All subjects were healthy siblings of patients undergoing hematopoietic transplantation for hematologic malignances, marrow failure syndromes, solid tumors, and congenital immune deficiencies. Donors gave assent/consent for participation in IRB-approved institutional protocols. Results: Donor age ranged from 3.8 to 17.8 years (mean 11.5 years), with 10 subjects (23%) under the age of 6 years, 15 (34%) between 7 and 12 years, and 19 (43%) between 12 and 17 years. Donor weight ranged from 16.1 to 59.1 kg (mean 38.6 kg). The cohort self-reported their ethnicity as 18 (41%) individuals being Hispanic, 16 (36%) Caucasian, 6 (13%) Black, and 3 (7%) Asian; 28 of 44 (63%) were female. G-CSF dose ranged from 7.6 to 16.7 mcg/kg, with 37 (84%) of the subjects receiving 9 to 13 mcg/kg (mean 10.2), and 6 (14%) receiving greater than 14 mcg/kg. Peak CD34+ count, assayed on a sample collected immediately prior to starting apheresis, was 75 ± 36 per mL (range 25 to 205/mL). A mean of 29.6 × 106 CD34+ cells (range 8.7 to 71.0) were harvested per liter processed, with 13.0 ± 5.4 liters processed per procedure (range 6.0 to 25.5 liters). In this manner, a total of 358 × 106 CD34+ cells (range 120–952 × 106) were collected per procedure, yielding a mean of 9.5 ×106 cells/kg recipient weight (range 3.17 to 20.8 ×106 cells/kg). Average procedural CD34+ collection efficiency was 57%. In univariate regression analysis, peak peripheral blood CD34+ counts on day 5 of G-CSF and CD34+ cell yields per liter processed during apheresis were significantly and negatively correlated with donor age (p=0.019), donor weight (p=0.011), and total CD34 dose (p=0.015). In contrast, peak circulating CD34+ counts were significantly higher in donors with higher baseline platelet (p=0.004) and mononuclear cell (p=0.027) counts. There was no significant relationship between donor gender or race and peak CD34+ mobilization response. In multivariate analysis, younger age was the single strongest factor associated with a favorable mobilization response (p=0.024); once age was in the model, donor weight and G-CSF dose no longer made significant contributions. In multivariate analysis, baseline platelet and mononuclear cell count (p=0.036 for both) continued to be strongly associated with a favorable mobilization response. Conclusions: In a healthy allogeneic pediatric population with an age range of 3 to 17 years, younger age is the driving factor determining the peak CD34+ mobilization response to G-CSF. Younger donors were smaller (lower weight) and thus received lower total doses of filgrastim, resulting in an inverse relationship between G-CSF dose and mobilization response, an opposite finding to that seen in adult PBSC donors. Higher baseline platelets and mononuclear cell counts were also predictors of more robust mobilization responses. Our data suggest that mobilizable cell reserves are greater in very young subjects, and that higher G-CSF dose or larger apheresis volumes are not necessary to achieve targeted cell yields in this population. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Platelet Decrease and Efficacy of Platelet-Rich Plasma Return for Peripheral Blood Stem Cell Apheresis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Takahiro Shima ◽  
Teppei Sakoda ◽  
Tomoko Henzan ◽  
Yuya Kunisaki ◽  
Takahiro Maeda ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Platelet Count ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Platelet Rich Plasma ◽  
Blood Stem Cell ◽  
Platelet Recovery ◽  
Platelet Counts ◽  
Cd34 Cells

Peripheral blood stem cell (PBSC) transplantation is a key treatment option for hematological diseases and widely performed in clinical practice. Platelet loss is the major complication of PBSC apheresis, and platelet-rich plasma (PRP) return is recommended in case of severe platelet decrease following apheresis; however, little is known about the frequency and severity of platelet loss nor the efficacy of PRP return post-apheresis. To address these questions, we assessed changes in platelet counts following PBSC-related apheresis in 270 allogeneic (allo)- and 105 autologous (auto)-PBSC settings. We also evaluated efficacy of PRP transfusion on platelet recovery post-apheresis. Platelet counts reduced up to 70% post-apheresis in both allo- and auto-PBSC settings, while severe platelet count decrease (< 50 x 109/L) was only observed in auto-PBSC patients (Figure 1). We next analyzed the relationship between severe platelet (< 50 x 109/L) after apheresis and several clinical factors by using univariate and multivariate analysis for auto-PBSC patients. As shown in Table 1, in univariate analysis, severe platelet counts following auto-PBSC apheresis was found more frequently in patients with lower platelet count, lower percentage of CD34+ cells in PB at pre-apheresis, repeated round of apheresis, and smaller number of collected CD34+ cells. On the other hand, in multivariate analysis, the white blood cell (WBC) counts pre-apheresis was the only significant risk factor of severe platelet count following apheresis (p = 0.038). We finally analyzed the transitions of platelet counts in the setting of apheresis. The median platelet counts at pre-apheresis, post-apheresis, and post-PRP return were 187.0 x 109/L, 132.0 x 109/L, and 154.0 x 109/L for allo-PBSC apheresis, and 147.0 x 109/L, 111.0 x 109/L, and 127.0 x 109/L for auto-PBSC apheresis (p < 0.0001 for all, allo-PBSC donors and auto-PBSC patients, respectively) (Figure 2), indicating that PRP return post-apheresis facilitated a rapid platelet recovery in both allo- and auto-settings. Collectively, our data suggest that WBC counts pre-apheresis is a useful predictor for severe platelet decrease following auto-PBSC apheresis and that PRP return is an effective mean to facilitate platelet recovery post-apheresis. Disclosures No relevant conflicts of interest to declare.

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.

Randomized comparison of progenitor-cell mobilization using chemotherapy, stem-cell factor, and filgrastim or chemotherapy plus filgrastim alone in patients with ovarian cancer.

1998 ◽  
Vol 16 (8) ◽  
pp. 2601-2612 ◽  
Author(s):  
A Weaver ◽  
J Chang ◽  
E Wrigley ◽  
E de Wynter ◽  
P J Woll ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Stem Cell Factor ◽  
Progenitor Cell ◽  
Randomized Study ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
High Yields ◽  
Higher Doses

PURPOSE This was the first randomized study to investigate the efficacy of peripheral-blood progenitor cell (PBPC) mobilization using stem-cell factor (SCF) in combination with filgrastim (G-CSF) following chemotherapy compared with filgrastim alone following chemotherapy. PATIENTS AND METHODS Forty-eight patients with ovarian cancer were treated with cyclophosphamide and randomized to receive filgrastim 5 microg/kg alone or filgrastim 5 microg/kg plus SCF. The dose of SCF was cohort-dependent (5, 10, 15, and 20 microg/kg), with 12 patients in each cohort, nine of whom received SCF plus filgrastim and the remaining three patients who received filgrastim alone. On recovery from the WBC nadir, patients underwent a single apheresis. RESULTS SCF in combination with filgrastim following chemotherapy enhanced the mobilization of progenitor cells compared with that produced by filgrastim alone following chemotherapy. This enhancement was dose-dependent for colony-forming unit-granulocyte-macrophage (CFU-GM), burst-forming unit-erythrocyte (BFU-E), and CD34+ cells in both the peripheral blood and apheresis product. In the apheresis product, threefold to fivefold increases in median CD34+ and progenitor cell yields were obtained in patients treated with SCF 20 microg/kg plus filgrastim compared with yields obtained in patients treated with filgrastim alone. Peripheral blood values of CFU-GM, BFU-E, and CD34+ cells per milliliter remained above defined threshold levels longer with higher doses of SCF. The higher doses of SCF offer a greater window of opportunity in which to perform the apheresis to achieve high yields. CONCLUSION SCF (15 or 20 microg/kg) in combination with filgrastim following chemotherapy is an effective way of increasing progenitor cell yields compared with filgrastim alone following chemotherapy.

When to harvest peripheral-blood stem cells after mobilization therapy: prediction of CD34-positive cell yield by preceding day CD34-positive concentration in peripheral blood.

1996 ◽  
Vol 14 (3) ◽  
pp. 970-973 ◽  
Author(s):  
C Elliott ◽  
D M Samson ◽  
S Armitage ◽  
M P Lyttelton ◽  
D McGuigan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Cell Number ◽  
Cell Yield ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells ◽  
Cell Mobilization ◽  
Wbc Count ◽  
Therapy Prediction

PURPOSE To evaluate whether the CD34+ yield from a single peripheral-blood stem-cell (PBSC) harvest could be predicted by measurement of the patient's circulating WBC and CD34+ cell concentrations on the day before harvest. PATIENTS AND METHODS Thirty-nine patients with hematologic or nonhematologic malignancy underwent 41 stem-cell mobilization episodes with cytotoxic chemotherapy and/or granulocyte colony-stimulating factor (G-CSF), and a total of 63 leukapheresis procedures were performed. Peripheral-blood samples were analyzed for WBC and CD34+ cell concentration both on the day before and the day of leukapheresis. RESULTS The median WBC and CD34+ concentrations on the day preceding leukapheresis were 10.0 x 10(9)/L (range, 0.4 to 44.4) and 24.9 x 10(6)/L (range, 0.1 to 349.4), respectively. On the day of harvest, the corresponding figures were 15.1 x 10(9)/L (range, 1.5 to 52.6) and 29.3 x 10(6)/L (range, 0.1 to 543.1), respectively. The median CD34+ cell number collected in a single leukapheresis was 2.6 x 10(6)/kg body weight (range, 0.1 to 26.1). Both the preceding day (r = .84, P < .001) and harvest day (r = .95, P < .001) CD34+ circulating concentrations correlated significantly with the number of CD34+ cells per kilogram collected at leukapheresis. The correlation between CD34+ cells per kilogram collected and harvest day WBC count was also significant (r = .43, P <.001), but with the preceding day WBC count was nonsignificant. CONCLUSION The number of CD34+ cells harvested in a single leukapheresis can be predicted by measurement of the preceding day peripheral-blood circulating CD34+ concentration, and on the basis of these data a table of probable CD34+ cell yield has been constructed. This correlation may facilitate the efficient organization of leukapheresis procedures.

The Role of Stem Cell Mobilization Regimen on Lymphocyte Collection Yield and Survival after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1174-1174 ◽  
Author(s):  
Luis F. Porrata ◽  
Suzanne R. Hayman ◽  
Morie A. Gertz ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Conditioning Regimen ◽  
Stem Cell Mobilization ◽  
Cell Labeling ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Cell Mobilization

Abstract We previously have reported that autograft absolute lymphocyte count (A-ALC) is a possible prognostic factor for survival after autologous peripheral blood stem cell transplant (ASCT) for myeloma (MM). Factors affecting A-ALC in MM are unknown. We hypothesize that method of stem cell mobilization, hematopoietic growth factor (HGF) vs. HGF+Cytoxan chemotherapy (C+HGF), directly affects A-ALC collection. 191 consecutive MM patients between 1994 and 2004 were analyzed retrospectively. Patients generally were mobilized with C+HGF prior to 2003. Thereafter, C+HGF was reserved largely for those with ≥4% circulating peripheral blood plasma cells (PC), a negative prognostic indicator. No patients were transplanted in disease relapse or refractory disease. Patients also were matched for age, sex, β2-microglobulin, conventional cytogenetics, LDH, c-reactive protein, number of prior therapies, plasma cell labeling index (PCLI), pre-mobilization ALC, and % bone marrow (BM) PC. The groups HGF (n=80) and C+HGF (n=111) differed with respect to the conditioning regimen (p &lt; 0.0001), and presence of (≥4%) circulating peripheral blood PC (p&lt;0.005). The primary end-point of the study was to assess the correlation between HGF vs C+HGF, and A-ALC. The secondary endpoint was to determine if HGF vs C+HGF affected survival post-ASCT. Patients mobilized with HGF had a higher A-ALC compared to those mobilized with C+HGF [0.764 x 109 lymphocytes/kg (range: 0.146–1.803) vs. 0.212 (range: 0.016–1.26), p&lt;0.0001]. No association was identified between A-ALC and conditioning regimens (p = 0.19) and PC (p = 0.31). Median overall survival (OS) and progression-free survival (PFS) were longer in those mobilized with HGF vs. C+HGF (not reached vs. 48 months, p&lt;0.0150; not reached vs. 21 months, p&lt;0.007, respectively). Multivariate analysis demonstrated that age ≥50 vs age ≤50 (p&lt;0.05) and A-ALC ≥0.5 vs &lt;0.5x109 lymphocytes/kg (p&lt;0.0397) were independent predictors of OS. Factors influencing PFS in the multivariate analysis included circulating PC ≥4% vs &lt;4% (p&lt;0.0157), PCLI ≥ 1% vs PCLI ≤ 1% (p&lt;0.0107), and A-ALC ≥0.5 vs &lt;0.5x109 lymphocytes/kg (p&lt;0.0042). On multivariate analysis, the method of stem cell mobilization and the conditioning regimen did not have a statistically significant effect on either OS or PFS. We hypothesize that the differences in PFS and OS seen between the HGF vs C+HGF mobilization groups are mediated through the A-ALC. These data suggest that mobilization regimens should not only collect CD34+ stem cells, but also be optimized to collect an A-ALC target which may impact on PFS and OS post-ASCT.

Long-Term Cryopreservation of Autologous Stem Cell Grafts: Impact of Patient Age, Initial Collection, and Stem Cell Mobilization Regimen.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1178-1178
Author(s):  
Hien Duong ◽  
Carol Dumont ◽  
Paul Elson ◽  
Edward A. Copelan ◽  
Brian J. Bolwell ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Mobilization ◽  
Cell Recovery ◽  
Storage Duration ◽  
Patient Age ◽  
Cell Counts ◽  
Patient Âgé ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 1178 Background: Effectively cryopreserving hematopietic peripheral blood progenitor cells (HPC(A)) until time of transplant is critical for successful autologous stem cell transplant. It is important to demonstrate long-term HPC(A) viability and recovery and also to identify patient characteristics that may influence this. We evaluated HPC(A) products cryopreserved over 16 year period. We analyzed potential correlations between total nucleated cell (TNC) and CD34+ recovery and viability and patient age, initial collection, and impact of stem cell mobilization regimen. Method: Samples were obtained from expired patients, chosen based on storage duration but randomly selected in regard to patient and product characteristics; 23 samples were obtained from 18 patients. Five patients had 2 samples each; for duplicate samples, data were averaged (collection dates and thaw dates were similar). All HPC(A) products were frozen in autologous plasma and 10% DMSO, then stored in liquid phase or vapor phase nitrogen. Products were uniformly thawed and washed to remove DMSO. Analysis included 7-Amino-actinomycin D viability, TNC and CD34+ cell counts and recovery. Some samples had post-thaw CD34+ cell counts that exceeded pre-thaw count; for these, the recovery was set to 100%. Spearman rank correlations were used to analyze association between the different parameters. Wilcoxon rank sum test and analysis of covariance were used to compare patient groups. Result: Median patient age at time of stem cell collection was 54 (range 2–75) years. A majority of patients had lymphoma (61%) or multiple myeloma (22%). Most (56%) were mobilized using G-CSF+VP16, 33% with G-CSF alone, and 11% other. Samples were cryopreserved for a median of 8 years (range 1–16). Median (range) for total CD34+ × 106 collected was 547 (43-5845). Median (range) for CD34+/kg × 106 was 8 (1-59). Median (range) count/bag for TNC × 108 was 144 (37-285) and for CD34+ × 106 was 105 (8-805). Median (range) recovery and viability were 85% (32-213%), and 70% (46-85%) respectively for TNC; and 97% (16-359%) and 80% (61-98%), respectively for CD34+ cells. Pre- and post- thaw TNC and CD34+ counts were both highly correlated (r=0.95, p<.0001 in both cases – figures 1a and b). There was no significant association between TNC recovery and viability (r=-0.07, p=.79) or between CD34+ cell recovery and viability (r=-0.21, p=.41). Storage duration did not impact CD34+ recovery or viability (r=-0.01, p=.98 and -0.18, p=.47, respectively); or TNC viability (r=-0.13, p=.62). There was, however a significant positive correlation between the storage duration and TNC recovery (r=0.81, p<.0001). Age did not significantly impact TNC or CD34+ recovery (r=-0.05, p=0.86, and r=-0.26, p=0.29, respectively); however there was suggestion of negative impact on viability (r=-0.45, p=0.06 and r=-0.42, p=0.08, respectively, figures 1a and 1b). Overall, there did not appear to be a correlation between the initial TNC count/bag or total CD34+ cell dose on recovery or viability (r=0.29, r=-0.22, r=0.18, r=-0.38, respectively; all p>0.12). However, when patients were stratified according to total collection >25×106 CD34+ cells/kg or ≤25 × 106 CD34+ cells/kg, there was better %CD34+ cell count recovery between groups (p = 0.07, median recovery 81% for 13 patients with ≤25 × 106 CD34+ cells/kg and 100% for 5 patients with >25×106 CD34+ cells/kg). For mobilization regimen, there was no significant difference in TNC recovery or viability (p = 0.19 and p=0.76, respectively) or CD34+ viability (p = 0.53), however there was suggestion that CD34+ recovery was greater with G-CSF+VP16 (p=0.06, see figure 2), independent of storage time. Conclusion: Products cryopreserved for 16 years retain acceptable recovery and viability. Unexpectedly, storage duration positively correlated with TNC recovery, and CD34+ cell recovery of >100% was noted in several samples. Reasons for this are unclear, but are likely related to changes in enumeration method or use of methods validated for counting fresh cells. Patient age was suggested to negatively impact post-thaw HPC(A) viability. Our data also suggested that the mobilization regimen or the CD34+ cell collection yield may affect the CD34+ cell recovery, possibly reflecting differences in graft characteristics. The number of patients included is relatively small and these findings warrant further studies for validation. Disclosures: No relevant conflicts of interest to declare.

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 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.

No Influence of Previous Thalidomide Administration on Peripheral Blood Stem Cell Collection in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4902-4902
Author(s):  
Iris Breitkreutz ◽  
Axel Benner ◽  
Friedrich W. Cremer ◽  
Doris Herrmann ◽  
Anthony D. Ho ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Total Dose ◽  
Induction Therapy ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Blood Stem Cell ◽  
Cd34 Cells ◽  
To Receive ◽  
Stem Cell Collection

Abstract OBJECTIVES: In a joint study of the GMMG and HOVON groups, induction therapy with Thalidomide (Thal), doxorubicin and dexamethasone (TAD) is currently investigated in comparison with vincristin, doxorubicin and dexamethasone (VAD) followed by mobilisation therapy with cyclophosphamide, doxorubicin and dexamethasone (CAD) and peripheral blood stem cell collection (PBSC). Munshi et al. (Blood 1999, Abstract #2577) described a dampening of PBSC-mobilisation by Thal treatment. We therefore investigated a possible influence of PBSC after previous Thal administration. METHODS: Altogether, data on 112 patients were analyzed in terms of PBSC-mobilisation. 56 patients were randomized up-front to receive 3 cycles of TAD (Thal 400mg/d orally; doxorubicin 9mg/m2/d, 4 30-min. infusions, day 1–4; dexamethasone 480mg total dose orally). 56 patients received VAD (vincristin 0,4mg/d and doxorubicin 9mg/m2/d, 4 30-min. infusions, day 1–4.; dexamethasone 480mg total dose orally) followed by mobilisation with CAD (cyclophosphamide 1g/m2/d, 1h infusion, day 1; doxorubicin 15mg/m2/d, 4 short infusions, day 1–4; dexamethasone 160mg total dose orally) and G-CSF (Neupogen 600mg/d s.c. or Granocyte 526mg/d s.c., day 5 after the end of chemotherapy until PBSC). Thal was stopped two weeks before CAD. Low dose heparine was administered to prevent deep venous thromboses in the TAD group. RESULTS: The median time was 14 days after the first day of CAD until PBSC in patients in both the TAD (range 12–18 days) and VAD group (range 10–19 days). In the first leukapheresis, a median total PBSC yield of 8,1x106/kg CD34+ cells in the TAD/CAD (range 0,3–34x106 CD34+ cells) and 8,7x106/kg CD34+ cells in the VAD/CAD (range 0,5–30x106 CD34+ cells) group could be harvested (p=0.31). In the best leukapheresis, a median total PBSC yield of 8,1x106/kg CD34+ cells in the TAD/CAD (range 0,7–34x106 CD34+ cells) and 8,9x106/kg CD34+ cells in the VAD/CAD (range 2–30x106 CD34+ cells) group could be reached (p=0.24). CONCLUSIONS: No difference was found in stem cell collection and yield after TAD versus VAD. Thalidomide as a part of induction therapy does not seem to have an influence of the peripheral blood stem cell collection of patients with multiple myeloma.

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