Autologous Stem Cell Mobilization with Cytokines and in-Vivo Alemtuzumab in Patients with T-Cell Non-Hodgkin's Lymphoma (T-NHL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3213-3213
Author(s):  
De Padua Silva Leandro ◽  
Rima Saliba ◽  
Donna McCormick ◽  
Grace-Julia Okoroji ◽  
Amin Alousi ◽  
...  

Abstract Abstract 3213 Poster Board III-150 Background The use of anti-CD20 monoclonal antibody during stem cell collection has significantly improved transplant outcomes in b-cell NHL. The CD52 antigen is expressed on T-NHL, making it a suitable target for immunotherapy programs, given the availability of the anti-CD52 alemtuzumab. Methods In this prospective trial, alemtuzumab was given at 3,10, 30 mg IV (days 1-3) and then 30 mg IV, 7 days later. G-CSF (10mcg/kg) and GM-CSF 250 mcg/m2 were provided daily, 5 days after starting alemtuzumab, and until a target of at least 2×106 CD34+ cells/kg was collected. Patients (pts) then underwent conditioning with standard BEAM. Results Sixteen pts [Peripheral T-cell (n=6); angioimmunoblatic (n=2); anaplastic large cell (n=4); hepatoslenic (n=2); NK/T (n=2)] were enrolled. Pts were required to have adequate counts (platelets >100K, ANC >1.5). Median age was 44 (range, 22-62) years. Median prior treatments was 1 (range,1-7). At study entry (SE), 8 pts (50%) were in first remission, 7 (44%) had chemosensitive relapse, and one pt had chemorefractory disease. Median IPI at SE, was 0 (range 0-1) and median marrow cellularity was 40% (ranged, 10%-90%). Five of 15 pts tested (33%) had marrow involvement at any time, and 3 of 8 tested (37.5%) had evidence of clonal T-cell by PCR at the time of SE. Eight pts (50%) failed to mobilize an adequate number of stem cells; a rate that is comparable to our historical control with cytokine mobilization alone in b-cell malignancies with rituximab (Am J Hematol 2009;84:335). The median time to start apheresis in the pts who were able to mobilize successfully was 4.5 (range, 2-7) days after initiation of cytokine administration. The median number of CD34×106/Kg collected was 5.9 (range, 4-13.5). The median number of collection days was 4(range, 2-6). Three of the failures underwent successful mobilization with chemotherapy, and 2 underwent marrow harvest. There was a trend for a higher risk of failure in pts who had received more > one chemotherapy regimen, those who had been exposed to Hyper-CVAD (4 of 5 failed), and those with bone marrow cellularity < 30%. Age did not appear to have had an impact. Due to small numbers however, none of these associations reached statistical significance. Only one of the 8 pts who mobilized developed ANC< 1500 and platelets <20K. Seven of the 16 pts experienced CMV reactivation (ELISA test) and responded to foscarnet therapy. Twelve pts (75%) were able to proceed to autologous transplantation. With a median follow-up time of 22 (range 1-47) months, overall survival and progression-free survival rates were 79% and 45%, respectively. Conclusions The use alemtuzumab with cytokines is safe and feasible during autologous stem cell collection. In order to decrease the risk of stem cell mobilization failures, futures trials incorporating either chemotherapy or plerixafor with the alemtuzumab are warranted Disclosures Khouri: Bayer Pharmaceuticals: Research Funding.

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5433-5433
Author(s):  
Jakub Radocha ◽  
Vladimir Maisnar ◽  
Miriam Lanska ◽  
Jiri Hanousek ◽  
Katerina Machalkova ◽  
...  

Abstract Stem cell mobilization after various induction regimens in patients with multiple myeloma Introduction: Rapid development of novel therapies for multiple myeloma has led to a significant improvement in response to the treatment. Stem cell mobilization before autologous stem cell transplantation is a source of considerable costs of transplant procedure. Whether modern induction regimens affect outcome of stem cell mobilization has not been extensively studied. Aim: The goal of this study was to compare efficacy of stem cell mobilization after different induction regimens in patients with multiple myeloma. The primary goal was to compare CTD (cyclophosphamide, thalidomide, dexamethasone), CVD (cyclophosphamide, bortezomib, dexamethasone) and VTD (bortezomib, thalidomide, dexamethasone) and regimens in terms of succesful stem cell collection. Methods: All patients with multiple myeloma who have been planned for stem cell collection and were treated with one of the above mentioned regimens were included in this retrospective analysis. The demographic data, amount of stem cells collected, number of days needed to reach the target collection were recorded. All patients received high dose cyclophosphamide 2,5 g/m2 prior to stem cell collection and were primed with G-CSF twice daily from day 5. The collection was started at day 10. Collection goal was 8x106/kg CD34+ cells. Results: 15 patients received CTD, 25 patients CVD and 16 patients VTD regimen before stem cell collection. Groups were comparable according to age, gender and myeloma stages. Mean collected cells at the end of collection were 9.2 (SD 2.8) for CTD, 12.3 (SD 5.6) for CVD and 10.1 (SD 2.1) for VTD (p=0.066). Mean daily harvest was 3.4, 8.0 and 7.6 x106/kg respectively (p=0.01). Mean days needed to reach desired harvest were 3, 2.25 and 1.6 days (p=0.001). No collection failure was observed. Conclusion: The best collection results were seen in patients after induction with CVD or VTD regimen. VTD regimen also required the least days for collection and seems to be most beneficial for cost of collection. CTD regimen shows the least efficacy in stem cell collection before autologous transplantation. All patients managed to harvest for at least one stem cell transplant. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2146-2146 ◽  
Author(s):  
Aziz Nazha ◽  
Rachel Cook ◽  
Dan T. Vogl ◽  
Patricia A. Mangan ◽  
Kimberly Hummel ◽  
...  

Abstract Abstract 2146 Poster Board II-123 Introduction: High dose melphalan and autologus stem cell transplant remains an effective treatment for patients with either early or refractory multiple myeloma (MM). Collection of sufficient numbers of stem cells for more than one transplant is optimal. G-CSF with chemotherapy, particularly cyclophosphamide (CY/G-CSF), has been a widely used and effective regimen for stem cell collection in MM. Plerixafor, a CXCR4 antagonist, when combined with G-CSF has been shown in a large randomized clinical trial to be superior to G-CSF alone. A comparison of plerixifor/G-CSF to CY/G-CSF is presented here. Materials and Methods: We performed a single institution retrospective analysis of 365 patients with MM who underwent stem cell mobilization and harvest at the University of Pennsylvania Abramson Cancer Center from January 2002 to December 2007. All patients were harvested early in the course of their disease. 76 patients were excluded from this analysis (23 had incomplete data on induction regimen, 19 had incomplete data on stem cell collection, 16 had incomplete data on mobilization regimen, 10 underwent allogeneic transplants, 2 had bone marrow rather than peripheral blood harvests, 2 had stem cells collected at an outside institution, 2 had chemotherapy mobilization other than CY and 2 had medical complications prior to harvest and after mobilization). Therefore, 289 patients were included in the analysis; 16 received plerixafor/G-CSF, 198 received CY/G-CSF, and 75 received G-CSF alone. Results: The median number of collected stem cells was 7.95 × 106 CD34+/kg in plerixafor/G-CSF group, 7.7 × 106 CD34+/kg in Cy/G-CSF group and 4.5 × 106 CD34+/kg in G-CSF alone group. The median number of apheresis days was 2 days, 2 days and 4 days respectively. The percentage of the patients who collected ≥ 6 × 106 CD34+/kg in < 3 apheresis was 63% (10/16), 62% (123/198) and 19% (14/75) respectively. The percentage of the patients who collected ≥ 6 × 106CD34+/kg <5 apheresis was 81% (13/16), 69% (136/198) and 23% (17/75) respectively. The mean CD34+/kg collected erither after CY/G-CSF or plerixafor/G-CSF was higher than G-CSF alone (p<0.0001 for each analysis). Conclusion: This analysis suggests that plerixafor/G-CSF and CY/G-CSF mobilization result in similar and adequate stem cell harvest numbers for autologous stem cell transplantation for MM. Both approaches are superior to G-CSF alone. The choice of plerixafor/G-CSF vs CY/G-CSF for stem cell mobilization will therefore depend on further analysis of the relative costs, toxicities and long term outcome of these regimens. Disclosures: Stadtmauer: genzyme: Consultancy.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3459-3459 ◽  
Author(s):  
Kristen Beyer ◽  
Samuel Rosner ◽  
Kaitlin M Woo ◽  
Sean M. Devlin ◽  
Heather Landau ◽  
...  

Abstract Background: The total therapy 3 protocol for multiple myeloma (MM) introduced the use of intensive induction with VDT-PACE, a combination of bortezomib, dexamethasone, thalidomide, cisplatin, adriamycin, cyclophosphamide, and etoposide for newly diagnosed MM patients. This regimen, which demonstrated rapid responses in the first-line setting, has also been used in relapsed disease, to rescue induction failures or for stem cell mobilization. We evaluated the efficacy and toxicity of using VDT-PACE in these clinical settings. Patients and Methods: We identified 84 patients through pharmacy profile review who received at least one cycle of VDT-PACE for the treatment of MM between 1/2007 and 8/2013 at our institution. Patients were grouped into a stem cell collection cohort (C) if stem cell pheresis was performed following VDT-PACE. Remaining patients were analyzed in the relapsed cohort (RR). The primary objective of this study was to determine the overall response rate with combination VDT-PACE. Secondary Objectives include progression-free survival (PFS), overall survival (OS), stem cell collection in patients that underwent chemomobilization, and the extent of toxicity. Results: In the RR group, 45 patients received VDT-PACE after a median of 4 prior therapies (range 1-8) including autologous stem cell transplantation (ASCT) in 79%. The median time between diagnosis and first cycle of VDT-PACE treatment was 35.4 months (range 1.3-163.4). 47% of patients had adverse cytogenetics defined as presence of complex karyotype or FISH with del 17p, t4;14, or t14;16. Patients received a median of 2 cycles of VDT-PACE (range 1-4) with a response rate after all cycles of 51% (2% CR, 22% VGPR, 27% PR). Additional therapy was administered in 82% within 6 months (18% allogeneic SCT, 35% ASCT, 29% chemotherapy regimens). 18% of patients died without additional therapy (13% from disease progression, 5% from toxicity), all within 5 months of their last VDT-PACE cycle. PFS and OS for the RR group was 8.8 months (95% CI 4.6, 13.1) and 10.3 months (95% CI 8.8, 17.4), respectively. Patients that received subsequent lines of therapy following VDT-PACE achieved a median PFS and OS of 9.5 months (95% CI 5.6, 13.3) and 9.5 months (95% CI 7.5, 32.1), respectively, measured from the time of next therapy. In the C group, 39 patients received a median of 2 prior regimens (range 1-4) before starting VDT-PACE and 31% of patients had adverse cytogenetics. Reasons for using VDT-PACE for mobilization included residual or progressive disease (64%), provider discretion (33%), and failure of a prior attempt at collection (3%). The median time between diagnosis and first cycle of VDT-PACE treatment was 7 months (range 2.3-122.7). Patients received a median of 2 cycles (range 1-4) of VDT-PACE. The median number of cells collected was 12.3x106CD34 cells/kg (range 0.21-43.74) and the median number of collection session required was 2 (range 1-6), with 21% of patients requiring plexirafor. Two patients (5%) from this group failed collection. The response rate after all cycles of VDT-PACE was 59% (3% CR, 13% VGPR, 44% PR). 35 out of the 39 patients went to transplant following VDT-PACE (34 ASCT, 1 allogeneic SCT). Of the 4 patients who did not receive transplant, 2 were for toxicity attributed to VDT-PACE, 1 for failure to mobilize, and 1 for personal reasons. The post-transplant response rate was 91% (17% CR, 34% VGPR, 40% PR) with 1 patient (3%) experiencing disease progression immediately after transplant. Median PFS and OS for the C group patients was 34.5 months (95% CI 20.2, n.r.) and 64.8 months (95% CI 26.0, n.r.), respectively. Reported toxicities following treatment included infection (20%), fatigue (19%), nausea (17%), renal complications (6%), thrombosis (4%), and edema (4%), which were seen in 67% and 62% of the RR and C groups, respectively. Hospital readmission for management of side effects occurred in 30% of patients. Conclusions: VDT-PACE is an effective therapy for RR patients and for stem cell mobilization in patients with residual or progressive disease following initial therapy. Importantly, it is also associated with significant morbidity and requires careful monitoring. VDT-PACE does not appear to adversely affect stem cell collection or SCT outcomes. At our institution, this regimen is commonly used for stem cell collection in patients with unfavorable outcomes following initial therapy. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 39 (S2) ◽  
Author(s):  
B. Mendibil Esquisabel ◽  
J. J. Ferreiro Martinez ◽  
I. Zeberio Etxetxipia ◽  
A. Altuna Mongelos ◽  
J. Iriondo Alzola ◽  
...  

2008 ◽  
Vol 14 (2) ◽  
pp. 103
Author(s):  
K.P.A. MacDonald ◽  
H.M. Bofinger ◽  
R.D. Kuns ◽  
E.S. Morris ◽  
A.L. Don ◽  
...  

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3281-3281
Author(s):  
Valerie Lapierre ◽  
Christian Chabannon ◽  
Caroline Makowski ◽  
Cecile Dumesnil ◽  
Dominique Valteau-Couanet ◽  
...  

Abstract Background: Ancestim (r-met human stem cell factor; Amgen Inc, CA, USA) is available in France for compassionate use in patients who have failed prior mobilization or an insufficient number of CD34+ cells for autograft. We retrospectively reviewed data from these patients to evaluate the efficacy of ancestim combined with filgrastim in achieving an adequate stem cell yield. Patients and methods: Between January 1998 and July 2007, permission for ancestim use was granted by the French health authority and Amgen to 550 patients (pts) at 82 sites (median age 55 yrs (range, 18–74); 50% male). Non-Hodgkin’s lymphoma (NHL) accounted for 50% of pts, multiple myeloma (MM) 28%, chronic lymphocytic leukaemia 6%, Ewing’s sarcoma 4%, neuroblastomas 3%, ovarian carcinoma 1%, osteosarcomas 1%, and other tumours 7%. Of the 508 pts for whom data were available and analysed, 378 had undergone prior mobilization and 117 were considered to have insufficient harvests; mobilization history was unknown for 13 pts. Fifty-eight percent of the pts were treated with ancestim (20 microg/kg/day s.c.) and filgrastim (10 microg/kg/day s.c.) alone for a median of 6 days (range, 2–21), while the other pts received chemotherapy followed by ancestim (20 microg/kg/day s.c.) and filgrastim (5 microg/kg/day s.c.) for a median of 11 days (range, 1–33). Results: The target threshold of 2x106 CD34+ cells/kg was reached in 198/508 pts (39%) (including 51% of the 144 MM pts and 31% of the 254 NHL pts) after a median of 2 leukaphereses (range, 1–6). 35% of pts with prior mobilization failure and 52% of pts with prior insufficient harvests reached the target of 2 x106 CD34+ cells/kg, with a median number of CD34+ cells harvested of 3.4 x106/kg (range, 0.5–39.5). Of these, 150 pts (76%) proceeded to autologous transplantation. Data on engraftment are available for 137 pts: the median times to reach 0.5 x 109/L neutrophils and 20 x 109/L platelets were 12 days (range, 6–40) and 13 days (range, 0–31), respectively. All pts receiving ancestim were premedicated and treatment was generally well tolerated. Four pts were reported to have experienced severe mast cell-mediated reactions, none of which were life-threatening. Conclusion: Ancestim plus filgrastim, alone or with chemotherapy, successfully rescued adequate CD34+ cell mobilization and collection in preparation for autologous transplantation in approximately 40% of pts.


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