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.

Timing of Daratumumab Administered Pre-Mobilization in Multiple Myeloma Impacts Pre-Harvest Peripheral Blood CD34+ Cell Counts and Plerixafor Use

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-16
Author(s):  
Danny Luan ◽  
Paul J Christos ◽  
Michael Ancharski ◽  
Danielle Guarneri ◽  
Roger Pearse ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Peripheral Blood ◽  
Research Funding ◽  
Stem Cell Mobilization ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Peripheral Blood Cd34 ◽  
Hematopoietic Recovery ◽  
Cell Mobilization

Background: Daratumumab (DARA) is a monoclonal antibody which targets CD38 on plasma cells and B cell progenitors. DARA has been effectively combined with other therapies in newly diagnosed and relapsed/refractory multiple myeloma (RRMM), while DARA-based induction regimens in transplant-eligible patients (pts) are increasingly being used in clinical practice. Given that hematopoietic stem cells also express CD38, DARA may potentially affect stem cell mobilization and hematopoietic reconstitution following autologous stem cell transplant (ASCT). Although no clinically significant impact of DARA on stem cell mobilization or hematopoietic recovery was described in large phase 3 trials of triplet induction regimens +/- DARA in newly diagnosed MM, stem cell yields were lower and plerixafor more commonly used in the DARA-containing arms [Moreau et al, Lancet 2019; Voorhees et al, Blood 2020]. Significantly longer time to neutrophil (PMN) engraftment was also reported in pts receiving DARA-based induction who underwent upfront ASCT [Al Saleh et al, Am J Hematol 2020]. In this study, we examine the impact of timing of DARA administration pre-mobilization on day 4 pre-harvest peripheral blood CD34 cell count, stem cell apheresis yield, and post-ASCT engraftment. Methods: Between 1/1/2016 and 12/31/2019, newly diagnosed and RRMM pts receiving DARA-based induction regimens with ≥1 dose of DARA administered within 1 month prior to stem cell mobilization were identified retrospectively and compared to matched controls receiving similar induction regimens without DARA. Granulocyte colony-stimulating factor (G-CSF) was administered per institutional standards and plerixafor added based on day 4 pre-harvest peripheral blood CD34 counts. PMN and platelet engraftment post-ASCT was defined as the first of 3 consecutive days with sustained PMN count &gt;500 x 106/L and independence from platelet transfusion in the preceding 7 days with a count &gt;20 x 109/L, respectively. Pre-harvest peripheral blood CD34 counts and stem cell apheresis yields were obtained from the Cellular Therapy Laboratory at NewYork-Presbyterian Hospital. The study was approved by the Weill Cornell Medicine IRB. Results: We identified 16 pts who received DARA-based induction with ≥1 dose of DARA administered within 1 month of apheresis (DARA group) and 16 non-DARA-containing regimen-matched controls (non-DARA group). Demographics of the DARA and non-DARA groups were well matched (Table 1). DARA pts received their last dose of DARA a mean of 17.3 days prior to the first day of apheresis, with 8 pts receiving their last dose within 2 weeks and the remaining 8 pts between 2 weeks and 1 month prior. Overall, mobilization outcomes were inferior in the DARA group (Table 2). DARA pts had significantly lower day 4 pre-harvest peripheral blood CD34 counts compared to non-DARA pts (17.2 vs 35.4 cells/µL; P=0.0146). Institutional algorithm required plerixafor to be given for day 4 CD34 count ≤40 cells/µL. Fifteen of the 16 DARA pts received plerixafor vs. 11 non-DARA pts (P=0.07). Additionally, DARA pts required significantly more apheresis days (2.4 vs 1.6 days; P=0.0279). Differences in stem cell yield were not significant (8 vs 10 x106cells/kg; P=0.1391). Hematopoietic recovery post-ASCT was not affected by DARA administered in the month preceding mobilization. Conclusions: In summary, we report lower day 4 pre-harvest peripheral blood CD34 count, increased requirement for plerixafor, and longer apheresis duration in newly diagnosed and RRMM pts receiving DARA within 1 month ofstem cell mobilization. These limitations are largely overcome by plerixafor usage which, combined with G-CSF, resulted in successful stem cell collection in all patients. Limitations in our study include small sample sizes, retrospective control selection, and fewer pts in the DARA group achieving ≥VGPR prior to mobilization. Nevertheless, our findings are consistent with inferior mobilization outcomes reported in the DARA-containing arms of phase 3 trials of triplet induction +/- DARA and highlight the nearly universal requirement for plerixafor usage when DARA is administered within a month prior to apheresis. Prospective study of day 4 pre-harvest peripheral blood CD34 counts and other predictors of stem cell yield should be incorporated into future clinical trials of CD38 monoclonal antibody-based induction regimens for transplant-eligible MM pts. Disclosures Rossi: Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Niesvizky:GSK: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Rosenbaum:Amgen: Research Funding; GlaxoSmithKline: Research Funding; Akcea: Honoraria; Celgene: Honoraria; Janssen: Research Funding.

Plerixafor and G-CSF For Autologous Stem Cell Mobilization In AL Amyloidosis: A Single Center Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4516-4516
Author(s):  
Esha Kaul ◽  
Gunjan L Shah ◽  
Chakra P Chaulagain ◽  
Raymond L. Comenzo
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Median Number ◽  
Initial Therapy ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Cd34 Cells ◽  
Cell Mobilization

Background Risk-adapted melphalan and stem cell transplant (SCT) is standard initial therapy for a minority of patients with systemic AL amyloidosis (Blood 2013;121: 5124; Blood 2011;118: 4298). Stem cell mobilization is often accomplished with high dose G-CSF (16μg/kg/d) (Blood 2011;118:4346). In the current era with effective new agents such as bortezomib, many AL patients are receiving initial therapy and achieving profound rapid cytoreduction with organ improvement (Blood 2012;119:4391; Blood 2011;118:86). But not all patients respond and in some cases the duration of response is limited. In addition, the use of SCT for consolidation after an initial response, although reasonable, has not been systematically evaluated. Whether SCT is employed as consolidation or as a second- or third-line option, the efficacy and tolerance of mobilization become important issues. Because AL patients have organ involvement limiting chemotherapy-based mobilization options, we decided to explore the option of Plerixafor and G-CSF for stem cell mobilization, based on the phase III experience in MM (Blood 2009;113:5720). We now report the first experience with this mobilization approach in AL. Patients and Methods Patients were evaluated and diagnosed by standard criteria including, in all cases, tissue biopsies showing amyloidosis. They were mobilized and collected between 4/16/12 and 6/19/13 with G-CSF 10μg/kg/d subcutaneously (SC) for 5 days (continued through collection process) and Plerixafor adjusted for renal function starting on day 4 and continuing until collection was completed. Results We report on 10 patients whose median age at mobilization was 58 years (range 46-72), 60% of whom were men. Median number of organs involved was 2 (range 1-3). Heart and kidneys were the most frequently involved organs (7 patients in each group). Median time from diagnosis to mobilization was 9 months (range 2-123). Eight patients had received prior bortezomib-based therapy. The median number of cycles was 3 (range 0-6). One had received a prior MEL 140 transplant 10 years prior and had relapsed, and 2 were treatment naïve, one of whom was 1 year status post orthotopic heart transplant. At the time of mobilization, 3 patients had non-responsive hematologic disease, 3 had achieved PR, 1 VGPR and 1 had achieved CR. Five patients had a creatinine ≥ 1.5 mg/dL including 2 patients on hemodialysis. The target cell dose was 10x106CD34/kg for all but one patient (with previous history of transplantation). The median number of collections was 2 (range 2-3). On day one, the median number of CD34+ cells collected per kg was 3.6 x106 (0.4-6x106) and on day two 6.4 x106 (2.7-19x106). The median total CD34+ cells collected per kg was 12.5x106 (5-18x106). Two patients had grade 1 bleeding from the catheter site during apheresis and one patient had dyspnea with suspected fluid overload which responded to a single dose of intravenous furosemide. There were no significant toxicities observed with Plerixafor in mobilization. All patients went on to receive high dose chemotherapy with melphalan followed by autologous stem cell transplant. The median length of hospital stay was 25 days (18-32). The median stem cell dose infused was 7.6x106CD34/kg and median days to ANC > 500 was 11 (10-22), to platelets > 20K untransfused 22 (15-44) and to lymphocytes > 500/μl 14.5 (11-25). One patient who had VOD and persistent thrombocytopenia was given the remainder of his stem cells on day +31 with full recovery and normalization of the blood counts by day +65. Conclusions In the era of more effective initial therapies, an era in which AL patients are living longer, many with moderate organ damage, mobilization with Plerixafor and G-CSF was well tolerated and made it possible to collect ample numbers of CD34+ cells with limited leukaphereses in previously treated patients and in those with advanced renal failure. This approach not only allowed the collection of sufficient CD34+ cells for optimal immediate stem cell dosing but also permitted the cryopreservation of aliquots for post-SCT boost and potentially for future cell-based therapies. Disclosures: Comenzo: Millenium: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Prothena: Research Funding; Teva: Research Funding.

Non Interventional Prospective Clinical Study on Peripheral Blood Stem Cell Mobilization in Patients with Relapsed Lymphomas

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3852-3852
Author(s):  
Gwendolyn van Gorkom ◽  
Herve Finel ◽  
Sebastian Giebel ◽  
David Pohlreich ◽  
Avichai Shimoni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Clinical Study ◽  
Research Funding ◽  
Median Number ◽  
Stem Cell Mobilization ◽  
Prospective Clinical Study ◽  
Cd34 Cells ◽  
Relapsed Lymphoma ◽  
Cell Mobilization

Abstract Introduction: Autologous stem cell transplantation (ASCT) is the standard of care for many patients with relapsed chemosensitive lymphoma. Peripheral blood stem cells have become the main source for the ASCT worldwide, because of its advantages over bone marrow. Several risk factors have been identified for poor stem cell mobilization, and diagnosis of lymphoma is one of the most important ones, with an inadequate stem cell harvest reported in 4 to 25% of the cases. Even though stem cell mobilization in relapsed lymphoma patients can be relatively difficult, mobilization strategies have not been standardized and there is a significant variation amongst centers. The aim of this non-interventional prospective clinical study was to review the mobilization strategies used by EBMT centers in relapsed lymphoma and to evaluate the failure rates. Methods: All EBMT centers were invited to participate in this non-interventional prospective clinical study that was started in 2010 and ended in 2014. Centers were requested to collect data on all consecutive patients with relapsed lymphoma considered to be candidates for an ASCT and were 18 years of age or older. Data collected included age, sex, diagnosis, number of prior chemotherapy regimens, mobilization regimen, collected CD34+ cells and marrow harvests. Results: In total, 275 patients with relapsed lymphoma from 30 EBMT centers were registered for this study. There were 158 males and 117 females with a median age of 51 (range 18 – 77) years; 181 patients (66%) with non-Hodgkin’s lymphoma (NHL) (DLBCL 28%, FL 17%, MCL 6%, PTL, 3%, other 12%) and 94 patients (34%) with Hodgkin’s lymphoma (HL). The median number of chemotherapy lines received before this relapse was one (range 1 – 8). 263 patients (96%) were mobilized with chemotherapy + G-CSF being DHAP (43%) and ESHAP (11%) the most frequent protocols, and 12 patients (4%) were mobilized with G-CSF alone. Thirteen patients (5%) who were mobilized with chemotherapy + G-CSF, received additional PLX in the first mobilization. These were all patients that were mobilized with chemotherapy as part of the mobilization regimen. Thirty patients (11%) failed to mobilize adequate stem cells (<2 x 10⁶ CD34+ cells/kg) during first mobilization despite the use of PLX in four patients. The median number of stem cells collected at first mobilization was 5.6 x 10⁶ CD34+ cells/kg (range: 0 – 82). In 255 patients (92.7%) only one mobilization course was given, 18 patients (6.5%) had two mobilization courses, 2 patients (0.7%) underwent three mobilization courses. Three patients had a mobilization failure after only G-CSF; they all were successfully harvested in a second attempt after chemotherapy + G-CSF. Five of the patients failing the first mobilization with chemotherapy + G-CSF received PLX at second mobilization, but only three succeeded. One patient failed both first and second mobilization and received PLX at third mobilization without success. 22 patients (8%) still had an inadequate amount of stem cells in the end. Of those, only 4 patients (1.5%) underwent bone marrow harvest. Conclusion: In the EBMT centers participating in this study, a primary mobilization strategy based on the combination of salvage chemotherapy plus G-CSF was used for virtually all patients with relapsed lymphoma. PLX was used in only 5% of the mobilization procedures during the time period analyzed. With 11% after the first mobilization attempt and 8% after several attempts, the failure rate was relatively low. Disclosures van Gorkom: Sanofi: Research Funding. Sureda:Takeda Pharmaceuticals International Co.: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics, Inc.: 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.

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.

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.

Peripheral Blood Stem Cell Collection In Patients Undergoing Induction Therapy with Lenalidomide Based Regimens: Failure Rates and Salvage Approaches

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2253-2253
Author(s):  
Shirshendu Sinha ◽  
Morie Gertz ◽  
Martha Lacy ◽  
Angela Dispenzieri ◽  
Suzanne Hayman ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Peripheral Blood ◽  
Research Funding ◽  
Colony Stimulating Factor ◽  
Advisory Committees ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Stimulating Factor ◽  
Stem Cell Collection

Abstract Abstract 2253 Background: Lenalidomide based combinations are among the most common initial therapies for myeloma. Previous studies have suggested that lenalidomide therapy can result in suboptimal stem cell collection in patients eligible to undergo autologous stem cell transplantation, especially older patients after prolonged exposure to the drug. Many salvage approaches are used when attempting repeat stem cell collection in this patient group. Patients and Methods: Two hundred twenty four patients who underwent stem cell collection following lenalidomide-dexamethasone induction from July 2004 and December 2009 were included in the current analysis. Data pertaining to the duration of lenalidomide therapy, stem cell mobilization regimen, and the collection yields were collected from the medical records. Results: The median age at mobilization was 60.6 years (range; 29, 76) and 136 (60%) were male. There were a total of 245 collection attempts from among 224 patients, 21 (9.8%) patients attempting to remobilize after failing to collect the desired numbers of stem cells at the first attempt. We first analyzed the results of the initial collection attempt. The median duration of lenalidomide therapy prior to stem cell collection was 4 months (range; 1, 26). The mobilization strategies were GCSF (Granulocyte Colony Stimulating Factor) alone in 151 (67%) patients, cyclophosphamide (CTX) followed by GCSF in 29 (13%) patients, and GCSF plus AMD3100 in 44 (20%) patients. Among those receiving AMD3100, it was added either due to peripheral blood CD34 cell count not reaching the threshold for initiation of harvest or for poor first day CD34 cells collection in 34 patients and given in a planned fashion in 10 patients. Overall 15 patients (7%) failed to reach the peripheral CD34 cell counts required to initiate apheresis, and among those starting apheresis 6 patients failed to collect at least 2 million CD34 cells/kg; a cumulative failure rate of 9%. Another 18 (8%) patients failed to collect at least 4 million CD34 cells /kg. The CD34 cells yield on day 1, the total yield, number of collections, the average daily yield and the percentage of the targeted cells collected for each mobilization strategy including failure rates are detailed in the table. Twenty-one patients reattempted stem cell mobilization; including 14 that failed a first attempt and 7 did who not achieve the intended goal even though they collected more than 2 million CD34 cells/kg. The mobilization regimens were GCSF alone, CTX + GCSF, GCSF + GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) and GCSF + AMD in 5, 8, 3, and 4 patients respectively. All patients collected at least 2 million CD34 cells /kg and 14 patients (70%) collected more than 4 million CD34 cells /kg. The median CD34 cells collected with the second attempt was 5.4 million/kg (rang; 2, 19.5) bringing the median total collection for these 21 patients to 9.6 million/kg (2.6-19.6). Overall, of the 224 patients studied, all but the 6 patients who failed initially and did not attempt a second collection collected at least 2 million CD34 cells /kg and 197 (88%) collected at least 4 million CD34 cells/kg. Conclusion: While the overall failure rate of stem cell collection in patients receiving initial therapy with lenalidomide is 10%, a risk adapted approach of adding AMD3100 appear to decrease the risk of failure. However, majority of patients failing a stem cell harvest attempt can be salvaged with a second collection allowing these patients to proceed to a stem cell transplant if desired. Disclosures: Gertz: Celgene: Honoraria; Millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genzyme: Research Funding. Lacy: Celgene: Research Funding. Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Micallef: Genzyme: Membership on an entity's Board of Directors or advisory committees. Kumar: Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

Cytopenia at Diagnosis Impairs Stem Cell Mobilization Among Patients with Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5828-5828
Author(s):  
Selami Kocak Toprak ◽  
Atilla Uslu ◽  
Erden Atilla ◽  
Pervin Topcuoglu ◽  
Gunhan Gurman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Risk Score ◽  
Induction Therapy ◽  
Peripheral Blood ◽  
Stem Cell Mobilization ◽  
Categorical Variables ◽  
Hematological Toxicity ◽  
Cell Mobilization ◽  
The Impact

Abstract Introduction: The GIMEMA group has recently developed a risk score predicting mobilization failure (Musto et al, EHA 2014). The risk score included age, cytopenia at diagnosis, induction therapy and their toxicity. In this study we aimed to evaluate the impact of these factors on peripheral blood stem cell (PBSC) mobilization among patients with multiple myeloma (MM). Patients and methods: 125 newly diagnosed patients with MM (M: 76, F: 49) planned for autologous stem cell transplantation; median age 58 years (range, 30-67) were included in the analysis. This retrospective study examined the impact of age (> 60 years), gender of the patients, cytopenia (Hb<10 gr/dL, absolute neutrophil count < 1x109/L, thrombocyte count < 100x109/L) at diagnosis, and severe hematological toxicity during induction therapy, the type of induction and mobilization methods, the presence of neuropathy, comorbid diseases such as diabetes mellitus, hypertension and renal failure (creatinine > 2 mg/dL), and the use of beta blocker drugs. Patients with CD34+ levels of <20/μL in peripheral blood at maximum stimulation were considered to be Poor Mobilizers. The total amount of PBSC <5x106/kg after a single mobilization procedure was defined as sub-optimal collection. Poor mobilization was observed in only two patients (<2x106/kg). Statistics: Comparison of categorical variables was evaluated by chi-square test or Fisher exact test. Nominal variables were compared with non-parametrical test, Mann-Whitney U or Kruskal Wallis test. P value below as 0.05 was accepted as significance. Results: Optimal mobilization with median two apheresis (1-4) sessions for PBSC was obtained in 85.6% of the patients (n=107). Median CD34+ cells in this group were 8.33x106/kg (5-27x106/kg). The presence of cytopenia at diagnosis was the only significantly detrimental factor on mobilization (90% vs 77.1%, p=0.04). When the patients was scored in four groups as having single or combined variables (age, cytopenia at the diagnosis or during induction therapy), we were not able to develop a risk score. Conclusions: In our experience, 14.4% of the myeloma patients showed suboptimal or poor mobilization. Use of bortezomib, age, presence of neurotoxicity or hematological toxicity at mobilization did not significantly impair mobilization. We were able to confirm only cytopenia at diagnosis, from the four factors reported by Musto et al, as a detrimental factor impairing the stem cell mobilization. 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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