Comparison of CXCR-4 and Adhesion Molecule Expression in Healthy Bone Marrow with Expression in Bone Marrow and Peripheral Blood of Patients Receiving G-CSF Plus AMD3100.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1974-1974
Author(s):  
Uta Oelschlaegel ◽  
Martin Bornhaeuser ◽  
Frank Kroschinsky ◽  
Gerhard Ehninger ◽  
Uwe Platzbecker
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Adhesion Molecules ◽  
Peripheral Blood ◽  
Surface Expression ◽  
Stem Cell Mobilization ◽  
Qualitative And Quantitative ◽  
Healthy Donors ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract It is known that the crosstalk between adhesion molecules, bone marrow microenvironment, and cytokines facilitates the multi step process of stem cell mobilization from bone marrow to peripheral blood. A combination of G-CSF plus AMD3100 - a CXCR-4 antagonist - has been shown to be safe and efficient in stem cell mobilization of healthy donors and cancer patients. Nevertheless, data predicting the efficacy of this approach are still missing. The present study investigated the correlation of the expression of CXCR-4 (CD184) and adhesion molecules with the kinetics and efficacy of stem cell mobilization in nine patients with Multiple Myeloma (MM) or NHL, respectively. Steady-state mobilization was performed using a combination of G-CSF (Filgrastim, 10μg/kg/d, 8 am) for 4 days followed by AMD3100 (240μg/kg) on day 4 at 10pm. Autologous aphereses were started on day 5. Bone marrow and peripheral blood (PB) before AMD3100 application (day 4) and PB on day 5 were investigated with a 4-color flow cytometric procedure. Bone marrow aspirates of healthy donors (n=20) served as control. The qualitative (%) and quantitative (mean fluorescence intensity, [MFI]) antigen expression of CXCR-4 in relation to CD34 was assessed as well as the expression of certain adhesion molecules including LFA-1, PECAM-1, VLA-1, L-selectin and CD44. First, the median percentage of CXCR-4 surface expression in healthy bone marrow was significantly higher (92%; range: 52 – 99%) than in patients bone marrow (70%; 30 – 88%; p=0.002), PB before AMD3100 (87%; 35 – 97%; p=0.050) and on day 5 (17%; 2 – 74%; p<0.001), whereas cytoplasmic expression was comparable (91%; 53 – 95%) in all cell compartments. The median quantitative CXCR-4 surface expression was significantly decreased in PB on day 5 compared to pre AMD3100 (14 vs. 95; p=0.003). Furthermore, the qualitative expression of LFA-1 and the quantitative expression of LFA-1, PECAM-1, VLA-1, and CD44 were also downregulated in response to AMD3100 (p<0.010). Second, a median of 63/μl (range: 15 – 132/μl) CD34+ cells was measured in the PB on day 5. Thus, a high absolute count of CD34+ cells in the PB on day 5 significantly correlated with lower qualitative and quantitative CXCR-4 expression in the same material (r=0.833; p=0.015). Evaluating CXCR-4 expression in bone marrow, PB before AMD3100 and on day 5 no significant correlation to CD34+ counts could be detected. However, there was one very poor mobilizing patient (15/μl CD34+ cells on day 5) in whom the quantitative CXCR-4 expression in the bone marrow was significantly higher than the median of all patients (MFI 95 vs. 26). Furthermore, some of the adhesion molecules (L-selectin, VLA-4, and CD44) showed a rather positive correlation with CD34 count. In summary, these preliminary data suggest that the amount of CD34+ cells in the peripheral blood after G-CSF plus AMD3100 application seems to be negatively correlated with CXCR-4 expression. A higher quantitative CXCR-4 expression in the bone marrow pre AMD3100 might predict a lower mobilization efficacy.

scholarly journals Dose-Adjusted Granulocyte Colony-Stimulating Factor Plus Dexamethasone Achieves More CD34+ Cell Mobilization and Earlier Engraftment in Haploidentical Hematopoietic Stem Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1966-1966
Author(s):  
Chenglong Li ◽  
Xi Yang ◽  
Jingying Dai ◽  
Ningning Tang ◽  
Hong Zheng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Hematopoietic Stem ◽  
Healthy Donors ◽  
Cd34 Cells ◽  
Significant Difference ◽  
Cell Mobilization

Introduction: Previous studies have showed that higher doses of CD34+ cell were associated with more rapid neutrophil and platelet engraftment, lower probabilities of graft rejection, as well as reduced transplant-related mortality. The aim of this study was to investigate the effects of G-CSF (Filgrastim) plus dexamethasone in CD34+ cell mobilization and engraftment in T-cell replete haploidentical hematopoietic stem cell transplantation(HHSCT) which was based on G-CSF-primed bone marrow and peripheral blood graft. Methods: A total of 79 healthy donors, who underwent bone marrow (BM) harvest and peripheral blood Stem Cells (PBSCs) collection between January 2015 and June 2019, were investigated. In G-CSF group, G-CSF was administered subcutaneously at a dose of 5μg/kg once a day from 1st to 5th day, while BM and PBSC were harvested on the 4th day and 5th day, respectively. In Dose-Adjusted G-CSF+Dex group, G-CSF was administered subcutaneously at a dose of 5μg/kg once a day on the 1st and 2nd day, then twice a day from the 3rd to 5th day; 5mg dexamethasone was injected intravenously before BM collection on the 4th day and before PBSC apheresis on the 5th day, respectively. All 79 recipients with hematological malignancies underwent HHSCT based on modification of BU/CY (busulfan/cyclophosphamide) and Anti-human T Lymphocyte Rabbit Immunoglobulin (ATG-F). All recipients received cyclosporine A, mycophenolate mofetil, and short-term cyclophosphamide as GVHD prophylaxis. Results: There were no significantly statistical differences between these two groups on characteristics of both recipients and donors. In Dose-Adjusted-G-CSF+Dex group, more mono nuclear cells (MNCs) were collected from BM and PB in comparison to the cells collected in the G-CSF group (p<0.001). There was a significant difference between the two groups on CD34+ cell counts from PB (p=0.002), which led to a significant difference on CD34+ cells in mixture allografts (p=0.04). In DA-G-CSF + Dex group, more CD34+ cells achieved earlier neutrophil (p=0.001) and platelet (p<0.001) engraftment compared with G-CSF group. Conclusion: Compared to G-CSF alone, dose-adjusted G-CSF plus dexamethasone on healthy donors can lead to more collection of MNCs and CD34+ cells in mixture allografts, which achieves earlier neutrophil and platelet engraftment. Disclosures Zheng: Pfizer: Research Funding.

Differences in the Expression of Adhesion Molecules and Mobilization Efficacy in Healthy Stem Cell Donors and Patients with Hematologic Malignancies.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2879-2879
Author(s):  
Uta Oelschlaegel ◽  
Kirsten Poppe-Thiede ◽  
Kristina Hoelig ◽  
Martin Bornhaeuser ◽  
Gerhard Ehninger ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Adhesion Molecules ◽  
Chemokine Receptor ◽  
Antigen Expression ◽  
Hematologic Malignancies ◽  
The Other ◽  
Stem Cell Mobilization ◽  
Healthy Donors ◽  
Cell Mobilization

Abstract Stem cell mobilization is achieved by short term administration of G-CSF in healthy donors and G-CSF +/− chemotherapy in patients with malignant diseases. It is known that the crosstalk between adhesion molecules, bone marrow microenvironment, and cytokines facilitates the multi step process of stem cell mobilization from bone marrow to peripheral blood. But still, the biological basis of the large variability in mobilization efficacy remains unclear. The aim of the present study was to evaluate if poor and good mobilizers - healthy donors as well as patients with hematologic malignancies - show differences in the expression of adhesion molecules (VLA-4, L-selectin, LFA-1, PECAM-1, CD44), the chemokine receptor CXCR4 and the G-CSF receptor measured by flow cytometry on CD34 positive cells. Therefore, we investigated 200 aphereses from 132 healthy PBSC donors and 68 patients with a 4-color staining: CD34/CD45 combined with two different adhesion molecules in each sample. The quantitative (mean fluorescence intensity) and qualitative (%) antigen expression was assessed. Donors/patients were divided into three groups according to the peripheral CD34-positive cell count at the day of apheresis: ≤ 30/μl (poor mobilizer; 36 donors, 30 pts.), 31–100/μl (standard mobilizer; 56 donors, 23 pts.), > 100/μl (good mobilizer; 40 donors, 15 pts.). The quantitative antigen expression was significantly higher for LFA-1 in poor vs. good mobilizing donors (GeoMean: 22 vs. 17; p=0.007) and patients (26 vs. 18; p<0.033) and for PECAM-1 (419 vs. 240; p<0.019; only in patients). In contrast, L-selectin showed a significantly lower expression in poor vs. good mobilizing donors (55 vs. 101; p=0.006). Considering the percentage of antigen positivity, LFA-1 was expressed in a significantly higher proportion of CD34 positive cells in poor mobilizing donors (66% vs. 53%; p=0.002) as well as patients (82% vs. 51%; p<0.011). In contrast, CXCR4 and L-selectin expression was significantly lower in samples of poor mobilizing patients (48 % vs. 62%, p<0.001; 90% vs. 95%, p=0.025). VLA-4, PECAM-1, and CD44 were expressed in 100% of CD34 positive cells independent of mobilization capacity. Comparing healthy donors and patients, the qualitative and quantitative adhesion molecule expression is much lower in donors vs. patients for almost all tested antigens and independent of mobilization efficiency. In contrast, the chemokine receptor CXCR4 has a significantly higher expression in CD34+ cells of healthy donors on the one hand, suggesting its downregulation during recovery from myeloablative chemotherapy in patients on the other hand. In summary, our analyses suggest that a higher LFA-1 expression is correlated with a reduced mobilization efficacy in healthy donors as well as patients with hematologic malignancies. The expression of the other tested antigen seems to be regulated differently in donors and patients.

Correlation of Cytokines Levels and Adhesion Molecules Expression with Stem Cell Mobilization Efficacy in Healthy Donors

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3466-3466
Author(s):  
Daniel Lysák ◽  
Alexandra Jungová ◽  
Jindra Vrzalová ◽  
Luboš Holubec ◽  
Vladimir Koza
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adhesion Molecules ◽  
Peripheral Blood ◽  
Odds Ratio ◽  
Healthy Donors ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Poor Mobilizers ◽  
Pbsc Mobilization

Abstract Peripheral blood stem cells (PBSC) are standard source of hematopoietic stem cells for allogeneic transplantations. Mobilization of PBSC in healthy donors is induced by a short term administration of G-CSF. The biological basis of the mobilization procedure in not completely discovered. Several factors were identified influencing the mobilization efficacy however their predictive potential for detection of poor mobilizers is limited. We performed a prospective study to evaluate differences in cytokines levels and adhesion molecules expression between good and poor mobilizers. The aim was to find out whether some of these factors can predict mobilization efficacy. Sixty healthy donors (25 related, 35 unrelated) were included in the study. The median age was 39 years (26–67). All donors were treated with G-CSF 10 μg/kg/day (filgrastim, Neupogen) for 5 days. Aphereses were started on day+5. Blood levels of certain cytokines (SDF-1, ICAM, VCAM, MMP-9, IL-6, IL-8, fractalkine, TNFα, VEGF, E-selectin) were tested before G-CSF application (day+0) and at first apheresis (day+5). Adhesion molecules expression (CD11a, CXCR4, CD44, CD117, CD26, CD49d) on CD34+ cells was measured at day +5. Cytokines were assayed by multiplex xMAP or ELISA technology. CD34 positive cells and adhesion molecules were evaluated with the flow cytometry using standard protocols. In response to the G-CSF stimulation the following cytokines significantly increased: ICAM (p<0.0001), VCAM (p<0.0001), MMP-9 (p=0.0039) IL-6 (p=0.0133), TNFα (p<0.0001) and E-selectine (p<0.0001). SDF-1 (p=0.0001), IL-8 (p=0.0013) decreased and fractalkine and VEGF remained unchanged. There was a positive correlation of day+5 SDF-1 (p=0.0011) and VCAM (p<0.0001) levels with CD34+ count at day+5. As for IL-6 borderline negative correlation (p=0.0861) between day+0 cytokine level and day+5 CD34+ count was found. Afterwards the donors were divided into two groups according to the CD34+ count at day +5. The cut-off of 40.0 CD34+ cells/μl was used for distinguishing of poor mobilizers. Twenty two percent (13 donors) mobilized below and 78 % (47 donors) above the cut-off. Between good and poor mobilizers there were significant differences of ICAM levels at day+0 (p=0.0369) and day+5 (p=0.0023), VCAM at day+5 (p=0.117) and IL-8 at day+5 (p=0.0473). Using logistic regression ICAM and IL-6 measured at day+0 (before stimulation) were tested as predictors of mobilization efficacy. The ICAM level below cut-off of 100 ng/mL implies approx. 5× higher risk of poor mobilization (odds ratio 4.8, p=0.0206). Conversely the IL-6 level above cut-off of 32 pg/mL means approx. 16× higher risk of poor mobilization (odds ratio 15.6, p=0.0112). Immunophenotyping of CD34+ cells suggested an inverse relationship of CD34+ counts with two adhesion molecules expression: CD11a (p=0.0002), CXCR4 (p=0.0075). However the expression of all tested antigens was similar in both donors groups. G-CSF stimulated PBSC mobilization results in increased plasma levels of some cytokines mostly evident for ICAM, VCAM, TNFα and decreased levels of SDF-1 and IL-8. In cases of ICAM and IL-6 the kinetics of these changes correlates with the quality of PBSC mobilization in peripheral blood. Their levels measured before G-CSF mobilization might serve as predictive factor for mobilization efficacy and graft quality. Contribution of adhesion molecules to stem cell mobilization is less clear and their practical utilization for mobilization course management is low.

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.

Bortezomib Given in Sequence with Anthracycline and Thalidomide-Containing Regimens Does Not Adversely Affect Stem Cell Mobilization and Engraftment in Patients with Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 541-541
Author(s):  
Geoffrey L. Uy ◽  
Nicholas M. Fisher ◽  
Steven M. Devine ◽  
Hanna J. Khoury ◽  
Douglas R. Adkins ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
High Dose Melphalan

Abstract Bortezomib (VELCADE®) is a selective inhibitor of the 26S proteasome proven to be safe and effective in the treatment of relapsed or refractory multiple myeloma (MM). While high-dose chemotherapy with autologous hematopoietic stem cell transplant (AHSCT) remains the standard of care, there is considerable interest in incorporating bortezomib into the initial treatment of MM. However, the role of bortezomib in frontline therapy for MM will depend in part on its effects on subsequent stem cell mobilization and engraftment. We conducted a pilot study of bortezomib administered pretransplant followed by high-dose melphalan with AHSCT. Two cycles of bortezomib 1.3 mg/m2 were administered on days 1, 4, 8, and 11 of a 21-day treatment cycle. One week after the last dose of bortezomib, stem cell mobilization was initiated by administering filgrastim 10 mcg/kg/day subcutaneously on consecutive days until stem cell harvest was completed. Stem cell collection began on day 5 of filgrastim via large volume apheresis (20 L/day) performed daily until a minimum of 2.5 x 106 CD34+ cells/kg were collected. Patients were subsequently admitted to the hospital for high-dose melphalan 100 mg/m2/day x 2 days followed by reinfusion of peripheral blood stem cells 48 hours later. Sargramostim 250 mcg/m2/day subcutaneously was administered starting day +1 post-transplant and continued until the absolute neutrophil count (ANC) ≥ 1,500/mm3 for 2 consecutive days. To date, 23 of a planned 40 patients have been enrolled in this study with 19 patients having completed their initial therapy with bortezomib followed by AHSCT. Patient population consists of 16 male and 7 female patients with the median age at diagnosis of 58 years (range 38–68). Myeloma characteristics at diagnosis were as follows (number of patients): IgG (16), IgA (7) with stage II (9) or stage III (14) disease. Prior to receiving bortezomib, 11 patients were treated with VAD (vincristine, Adriamycin and dexamethasone) or DVd (Doxil, vincristine and dexamethasone), 5 patients with thalidomide and 5 patients with both. Two patients did not receive any prior chemotherapy. All patients successfully achieved the target of 2.5 x 106 CD34+ cells/kg in either one (15/19 patients) or two (4/19 patients) collections with the first apheresis product containing a mean of 5.79 x 106 CD34+ cells/kg. Analysis of peripheral blood by flow cytometry demonstrated no significant differences in lymphocyte subsets before and after treatment with bortezomib. Following AHSCT, all patients successfully engrafted with a median time to neutrophil engraftment (ANC ≥ 500/mm3) of 11 days (range 9–14 days). Platelet engraftment (time to platelet count ≥ 20,000/mm3 sustained for 7 days without transfusion) occurred at a median of 12 days (range 9–30 days). Eleven patients were evaluable for response at 100 days post-transplant. Compared to pre-bortezomib paraprotein levels, 3 patients achieved a CR or near CR, 7 maintained a PR while 1 patient developed PD. We conclude that pretransplant treatment with 2 cycles of bortezomib does not adversely affect stem cell yield or time to engraftment in patients with MM undergoing AHSCT. Updated results and detailed analysis will be available at the time of presentation.

A Retrospective Evaluation of the Impact of Pre-Emptive Plerixafor Administration on Collection Efficiency in Patients with Myeloma Undergoing Stem Cell Mobilization

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5740-5740 ◽  
Author(s):  
Leslie A. Andritsos ◽  
Ying Huang ◽  
Tao Fan ◽  
Keith Huff ◽  
Ed Drea ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Research Funding ◽  
Collection Efficiency ◽  
Treatment Algorithm ◽  
Stem Cell Mobilization ◽  
Cell Dose ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
The Impact

Abstract Background: High dose melphalan with autologous stem cell support (aSCT) remains one of the most beneficial therapies for myeloma. However, this therapy may be limited by the ability to collect a minimum CD34+ cell dose of 2.0 × 106/kg. Failure to collect an adequate CD34+ cell dose leads to significantly increased costs and treatment delays. Plerixafor (PL) is a mobilization agent which reversibly inhibits binding of SDF-1 to the chemokine receptor CXCR4, resulting in mobilization of hematopoietic progenitor cells. Phase 3 studies demonstrate that administration of PL significantly improves the likelihood of successful CD34+ cell collection compared to G-CSF alone (Dipersio, Blood 2009) in patients with myeloma and NHL. In order to improve collection efficiency, our center began a policy of PL administration to all myeloma patients undergoing collection pre-emptively on the evening prior to Day 1 of collection. Herein we evaluate the outcomes of that policy change when compared to patients who received PL on Day 1 (D1) of collection according to a treatment algorithm which evaluated peripheral blood (PB) CD34+ cell number as well as D1 CD34+ cell dose collection. Methods: Patients with myeloma undergoing mobilization who received PL during their treatment course were eligible. Patients were categorized according to timing of administration to either pre-emptive (P-PL) or standard (S-PL), which was given according to a treatment algorithm on day 1 of collection based on CD34+ cell dose. Patients were evaluated for total CD34+ dose procured, number of apheresis procedures, risk factors for poor mobilization and collection (age, prior therapies, and DM), and pre-emptive vs. standard PL. A multivariable logistic regression model was built to predict the ability to achieve minimum collection goal. Results: From 2009 to 2014, 299 patients received PL during stem cell mobilization and were available for evaluation. Of these, 241 received P-PL and 58 received S-PL. There were no significant differences between patient groups with respect to sex, age, race, KPS, ISS score, CMI, # of prior therapies, prior lenalidomide, DM-2, or disease status at the time of transplant. As expected, patients who received P-PL had significantly better collection. Patients who received P-PL had a median CD34+ peripheral blood cell count (absolute) on the day before collection of 21 (range 0-162) vs. 8 for S-PL (range 3-90, p<0.0001). Median total CD34+ cell dose collected on D1 of collection was 6.75 in the P-PL group vs 1.96 in the S-PL group (p<0.0001). There was no significant difference in collection efficiency for days 2 and 3 of collection between the groups. There was no difference between the numbers of doses of PL received, with both groups receiving a median of 1 dose (range 1-3 for both). The majority of P-PL patients completed collection in 1-2 collections (99%) vs. 64% for S-PL (p<0.0001). With respect to engraftment, there were no differences between the groups for platelet engraftment to 20,000/mcl, however patients in the P-PL group had a significantly longer ANC engraftment time (11 vs. 10 days, p<0.0001), possibly explained by a change in post-transplant filgrastim administration to day +7 which occurred during that time; these patients also had a longer hospital stay, possibly for the same reason. On univariable analysis, pre-emptive PL was the only factor significantly associated with likelihood of collection of at least 2.0 x 106 CD34+ cells/kg on first collection (p<0.0001). On multivariable analysis, factors significantly associated with collection of at least 2.0 x 106 CD34+ cells/kg on D1 included P-PL (p<0.0001), CR or PR at the time of collection (p=0.03), and DM-2 (p=0.05). Two patients in the P-PL group failed to collect 2.0 x 106 CD34+ cells/kg by day 4 of collection despite this up-front strategy; the cell doses collected were 1.91 x 106 and 1.99 x 106. Conclusions: Up-front administration of PL significantly enhances collection efficiency, with the majority of patients (77%) completing collection in one day. Disclosures Andritsos: Hairy Cell Leukemia Foundation: Research Funding. Fan:Sanofi: Employment. Drea:Sanofi: Employment. McBride:Sanofi: Research Funding.

scholarly journals Bortezomib in Combination with Cyclophosphamide and G-CSF for Hematopoietic Stem Cell Mobilization in Patients with Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2067-2067 ◽  
Author(s):  
Bhausaheb Bagal ◽  
Anant Gokarn ◽  
Avinash Bonda ◽  
Swapnil Chavan ◽  
Sachin Punatar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Cell Yield ◽  
Hematopoietic Stem ◽  
Peripheral Blood Cd34 ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Cell Harvest

Abstract Background: Proteasome inhibitors (PI) have become integral part of front-line treatment of multiple myeloma. Murine model experiments have shown mobilization of hematopoietic stem cells from bone marrow to peripheral blood after PI administration via down regulation of very late antigen 4 (VLA-4) which mediate adherence of hematopoietic stem cells to the bone marrow microenvironment via interaction with vascular cell adhesion molecule (VCAM-1). Human studies with bortezomib in combination with G-CSF for mobilization have yielded encouraging results with no additional toxicity and no malignant plasma cell mobilization was observed. Cyclophosphamide based chemo-mobilization offers advantage in term of higher stem cell yield and is able to overcome adverse impact of prior lenalidomide therapy on stem cell harvest. In the current study we added bortezomib to cyclophosphamide-GCSF (B-Cy-GCSF) chemo-mobilization regimen to study the effect of bortezomib on stem cell harvest and compared this with our earlier protocol of only cyclophosphamide-GCSF (Cy-GCSF) mobilization. Methods: Patients of multiple myeloma aged between 18 to 70 years were eligible for the study in the period between March 2016- June 2018. Patients after induction therapy achieving at least partial response and having no more than grade 1 peripheral neuropathy were enrolled. Patients received bortezomib at a dose of 1.3 mg/m2 on day 1, 4, 8 and 11 and cyclophosphamide (Cy) was administered at a dose of 1 g/m2 on day 8 and 9 followed by G-CSF 10µg/kg in two divided doses from day 11 onwards till target stem cell collection of at least 5 X 106/Kg. The peripheral blood CD34 (PB CD34) counts were monitored from day 14 and harvest was initiated when it reached above 20 cells/µL. The peak PB CD34 count achieved, the number of days of harvest required, the CD34 dose yield and the engraftment kinetics were recorded and compared with earlier patients who had undergone Cy-GCSF chemo-mobilization. These patients had received Cy 1 g/m2 on d1 and d2, G-CSF 10 mcg/kg from d4 onwards and PBCD34 monitored from d7 onwards. Result: A total of 37 patients were enrolled between March 2016 and June 2018. Median age of study cohort was 46 years (range 27-63) and 27 (73 %) were males. Median lines of therapy received were 1 (range 1 to 2) and 8 (21.6 %) had received lenalidomide prior to stem cell harvest. The median peak peripheral blood CD34 cell counts 71.3 cells /µL (range 27.5 -306). Median CD34 cells collected were 9.21 X 106 /Kg (range 4.95-17.1). Target CD34 cell collection was achieved after a median of one day harvest (range 1-2). Median time to neutrophil and platelet engraftment was 11.5 and 13.5 days respectively. These results were compared with 88 patients who had undergone Cy-GCSF chemo-mobilization earlier at our center from May 2008 till February 2016 as seen in Table1 . In Cy- G-CSF cohort, median number of harvest required for target CD34 was 2 (range 1-4) and median CD34 cell yield was 8.2 X 106/Kg (0.4-24.2). Target CD34 cells yield of 5 X 106/Kg was achieved with single apheresis in 58.6% of patients after B-Cy-GCSF mobilization as compared to 44.3% in Cy-G-CSF group, although this was not statistically significant (p=0.1). While 3(3.4 %) had failed chemo-mobilization after Cy-GCSF, none of patients in bortezomib group had mobilization failure. Conclusion: Patients undergoing B-Cy-GCSF mobilization have higher stem cell yield and required less days of harvest. This strategy should be explored in a larger cohort of patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Plerixafor for Autologous Peripheral Blood Stem Cell Mobilization in Patients Previously Treated with Fludarabine or Lenalidomide

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1932-1932
Author(s):  
Florent Malard ◽  
Nicolaus Kröger ◽  
Ian H Gabriel ◽  
Kai Hübel ◽  
Jane F. Apperley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Peripheral Blood ◽  
Median Number ◽  
Stem Cell Mobilization ◽  
Non Hodgkin Lymphoma ◽  
Cd34 Cells ◽  
Previously Treated ◽  
Cell Mobilization ◽  
Autologous Hsct

Abstract Abstract 1932 High dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) is an effective treatment for patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). At present, G-CSF-mobilized peripheral blood stem cells (PBSCs) are the preferred stem cell source for autologous HSCT. Fludarabine and lenalidomide are essential drugs in the front line treatment of NHL and MM respectively. Data suggests that fludarabine and lenalidomide therapy may have a deleterious effect on stem cell mobilization. Prior to the drug approval in Europe, a plerixafor compassionate use program (CUP) was available from July 2008 to August 2010 to provide access to the drug for patients with MM or lymphoma who had previously failed a mobilization attempt, and who were not eligible for another specific plerixafor trial. In the European CUP, 48 patients (median age 57 years; range, 36–69), previously treated with fludarabine (median 5 cycles; range, 1–7 cycles) were given plerixafor plus G-CSF for remobilization following a primary mobilisation attempt. All 48 patients had a diagnosis of NHL. The overall median number of CD34+ cells collected was 2.3×106 /Kg (range, 0.3–13.4). The minimum required number of CD34+ cells (≥2.0×106 per kg) was collected from 58% of patients, while only 3 patients (6%) collected ≥5.0×106 CD34+ cells. The collection target of 2.0×106/Kg was reached in a median of 2 apheresis sessions (range, 1–3). Thirty-five patients (median age 57 years; range, 34–66), previously treated with lenalidomide (median 5 cycles; range, 1–10 cycles) were given plerixafor plus G-CSF for remobilization. All patients the 35 patients had MM. The overall median number of CD34+ cells collected was 3.4×106/Kg (range, 1.1–14.8). The minimum required number of CD34+ cells (≥2.0×106 per kg) was collected from 69% of patients, including 12 patients (34%) who were able to collect ≥5.0×106 cells/Kg. In the Len group, 7 patients (20%) had received a prior autologous HSCT before salvage mobilization with plerixafor. Both targets were reached with a median of 2 apheresis sessions (range, 1–4). In conclusion, salvage mobilization with plerixafor plus G-CSF is successful in the majority of patients with MM previously treated with lenalidomide. In fludarabine-exposed patients, only 58% of patients will achieve successful salvage mobilization with plerixafor plus G-CSF, suggesting the need for large prospective studies evaluating the efficacy of plerixafor for frontline mobilization in this subgroup of patients.Table 1.Study population characteristicsCharacteristic (%)Fludarabine (N=48)Lenalidomide (N=35)Patient age, median (range)57 (36–69)57 (34–66)Patient gender    Male26 (54)18 (51)    Female22 (46)17 (42)Fludarabine or Lenalidomide cycles, median (range)5 (1–7)5 (1–10)Diagnosis and disease statusIndolent NHL48 (100)0 (0)Multiple myeloma0 (0)35 (100)Previous chemotherapy: number of lines, median (range)3 (1–6)4 (1–9)Previous autograft    Yes07 (20)    No43 (90)20 (57)    Data missing5 (10)8 (23)Radiotherapy    Yes5 (10)3 (9)    No36 (75)24 (68)    Data missing7 (15)8 (23)Mobilization strategy with plerixafor    Steady-state GCSF mobilization38 (79)27 (77)    Chemotherapy+GCSF mobilization10 (21)8 (23)No. of patients collected44 (92)34 (97)CD34+ cells collected per Kg, median (range)2.3 (0.3–13.4)3.4 (1.1–14.8)No. of patients who reached ≥ 2.106 CD34+28 (58)24 (69)No. of apheresis days to reach ≥ 2.106 CD34+2 (1–3)2 (1–4)No. of patients who reached ≥ 5.106 CD34+3 (6)12 (34)No. of apheresis days to reach ≥ 5.106 CD34+2 (1–3)2 (1–3)NHL, non-Hodgkin lymphoma Disclosures: Mohty: Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Allogeneic Stem Cell Transplantation with Peripheral Blood Stem Cells Mobilized by Pegylated-G-CSF.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1970-1970
Author(s):  
Geoff Hill ◽  
Edward S. Morris ◽  
Maddona Fuery ◽  
Cheryl Hutchins ◽  
Jason Butler ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Cell Function ◽  
Ideal Body Weight ◽  
Stem Cell Mobilization ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
12Mg Dose

Abstract The mobilization of stem cells with pegylated-G-CSF (peg-G-CSF) modulates regulatory T cell and NKT cell function, separating graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects in animal models. We have initiated a phase I/II study to analyse the feasibility of mobilizing stem cells from sibling donors with peg-G-CSF and their ability to restore hematopoiesis in HLA matched transplant recipients who have received myeloablative conditioning. Results were compared to a cohort of donors mobilized with standard G-CSF at 10ug/kg/day (n=19). The administration of 6mg of peg-G-CSF (n=6) resulted in suboptimal stem cell mobilization with a peak peripheral blood CD34+ count of 29 ± 4/uL. Apheresis 4 days after peg-G-CSF administration yielded 2.7 ± 0.3 x106 CD34+ cells/kg recipient ideal body weight and all patients required a second collection on day 5 to yield a total of 4.0 ± 0.5 x106 CD34+ cells/kg recipient weight. Following escalation of the dose to 12mg (n=9), the peak CD34+ count was 109 ± 13/uL and all donors collected sufficient stem cells for transplantation in a single apheresis (9.8 ± 1.7 x106 CD34+ cells/kg recipient weight). The 6mg dose of peg-G-CSF was significantly inferior to standard G-CSF for stem cell mobilization (P<0.01) while the 12mg dose was at least equivalent (P=0.07). Bone pain was similar between the 6mg and 12mg cohorts and to that seen with standard G-CSF. However, in addition to the expected rises in serum ALP and LDH, transient rises in hepatic transaminases were noted 5 to 12 days after peg-G-CSF administration in 7 of 9 donors receiving the 12mg dose. One donor developed NCI grade 3 hepatic toxicity and splenomegaly. After allogeneic transplantation of peg-G-CSF mobilized grafts (Cy/TBI conditioning in 13 of 14 recipients), median neutrophil and platelet engraftment occurred on days 18 and 14 respectively and was identical to that seen with grafts mobilized by standard G-CSF. With a median follow up of 165 days (range 55–532), the incidence of grade II-IV and grade III/IV acute GVHD is 50% and 21% respectively. No patients have relapsed to date and overall survival is 86%. The mobilization of stem cells with peg-G-CSF in normal donors is feasible and 12mg appears the optimal dose. Further data are required to more closely analyse the effect of peg-G-CSF on donor liver function and the ability of stem cell grafts to separate GVHD and GVL effects. Figure Figure

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