scholarly journals A Randomized Evaluation of Vinorelbine Versus Gemcitabine Chemotherapy Mobilization of Stem Cells in Myeloma Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1963-1963
Author(s):  
Barbara Jeker ◽  
Sarah Farag ◽  
Urban Novak ◽  
Ulrike Bacher ◽  
Behrouz Mansouri Taleghani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Conflicts Of Interest ◽  
Group Versus ◽  
Promising Alternative ◽  
Randomized Evaluation ◽  
Prospective Comparison ◽  
Prospective Phase ◽  
Cell Mobilization ◽  
Grade 3

Background: In myeloma patients, a non-myelosuppressive regimen combining a single dose of vinorelbine chemotherapy together with G-CSF is safe and effective to harvest peripheral blood progenitor and stem cells (PBSC) before autologous stem cell transplantation (ASCT). Considering its neurotoxic potential, vinorelbine may aggravate pre-existing bortezomib-induced polyneuropathy, and gemcitabine represents an alternative mobilization regimen. We have reported that monotherapy with gemcitabine together with G-CSF can be used as a promising alternative mobilization chemotherapy to vinorelbine, even more so as gemcitabine avoids neurotoxicity associated with vinorelbine Methods: In this prospective phase-II study (ViGeM Trial; NCT# 02791373), we compared in a 1:1 randomization the efficacy and toxicity of vinorelbine or gemcitabine with G-CSF (and, if needed, plerixafor) in 130 evaluable myeloma patients in first remission. The objective of the study is to demonstrate the non-inferiority of gemcitabine versus vinorelbine. The primary endpoint is mobilization success, which is defined as a collected apheresis product comprising at least 6.0×106 CD34+ cells/kg b.w. at day 8 after chemotherapy (vinorelbine or gemcitabine) together with G-CSF in the absence of plerixafor. Results: We observed successful CD34+ mobilization in 75% [95% confidence interval (CI): 63%-85%] of patients in the vinorelbine group versus 49% [95% CI: 36%-62%] with gemcitabine; the pre-specified non-inferiority margin -15% was not reached. More vinorelbine recipients achieved the collection goal in a single-day procedure (78% vs 60%). The median CD34+ yield was 11.4×106/kg b.w. in vinorelbine versus 8.7×106/kg in gemcitabine (P=0.001). At apheresis as well as day +100 following ASCT, polyneuropathy occurred more frequent in vinorelbine recipients. Special attention should be given to the fact that no patients with gemcitabine was observed with grade ≥ 3 polyneuropathy (Table 1). Finally, less patients in the vinorelbine group (1%) needed two apheresis days as compared to 14% in the gemcitabine group, respectively (P=0.007), whereas the use of rescue plerixafor was similar (11% versus 10%). Conclusion: This prospective comparison indicated that non-inferiority of gemcitabine as compared to vinorelbine chemotherapy together with G-CSF stimulation regarding CD34+ mobilization was not reached. Polyneuropathy was aggravated in the vinorelbine cohort, but not in gemcitabine recipients. Our study allows individualization of CD34+ mobilization regimens in myeloma patients. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Vinorelbine and gemcitabine are used for stem cell mobilization in this study and, thus, off-label.

Prominin-1 Mobilisation, Collection and Immunoselection in Cancer Patients for Liver Regeneration.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2141-2141
Author(s):  
Cesare Perotti ◽  
Claudia Del Fante ◽  
Gianluca Viarengo ◽  
Marcello Maestri ◽  
Laura Salvaneschi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Side Effects ◽  
Liver Cancer ◽  
Liver Regeneration ◽  
Cancer Patients ◽  
Conflicts Of Interest ◽  
Stem Cell Mobilization ◽  
Hematopoietic Stem ◽  
Cell Mobilization

Abstract Abstract 2141 Poster Board II-118 Background: CD133+ (Prominin-1 positive) is a 5-transmembrane glycoprotein that identifies immature progenitor stem cells. Immature hematopoietic stem cells retain the possibility to give origin to tissues different from hematopoietic cell lines (transdifferentiation). Material and methods: In this preliminary study we investigated the possibility to mobilize, collect, immunoselect and reinfuse autologous CD133+ immature stem cells in liver cancer patients. This approach was adopted to obtain, in a short time, an adequate volume increase of the disease free liver thus extending the resectability criteria of the liver, with the final goal to prolong survival. We enrolled 4 patients with a large liver cancer and no chance of resection. The mobilization protocol consisted in: G-CSF administration (10 μg/kg/day ) for 3-5 days, peripheral blood stem cell (PBSC) monitoring starting from the 3rd day, leukapheresis (LKF) collection processing 3 blood volumes when CD133+ cells>15 μL. Patients were monitored during mobilization, collection and post collection phase for clinical status, blood pressure and bleeding. Positive CD133+ immunoselection (Miltenyi Clinimacs) was performed on LKF product after overnight storage. Quality controls on positive fraction consisted in viability and purity of CD133+ cells by cytofluorimetric analysis and clonogenic assays. Microbial tests were performed on the negative fraction. After LKF, patients underwent right portal embolization and infusion of CD133+ cells into the opposite portal vein by a percutaneous access. Evaluation of liver regeneration was performed 30 days after stem cell infusion by spiral CT and galactose clearance. Liver resection was carried out if liver regeneration reached 30-40%. Results: Stem cell mobilization, LKF content and immunoselected cells are detailed in tab 1. No relevant side effects were observed. We obtained an efficient stem cell mobilization in all patients enrolled. No bacterial or fungal contamination was observed in cells infused. Results about liver regeneration and patients' follow up are detailed in table 2. Conclusions: Our approach to liver regeneration was feasible and safe with no relevant side effects. We observed an efficient stem cell mobilization comparable to healthy donors also in liver cancer patients. The infusion of CD133+ cells allowed a significant hepatic tissue regeneration in all patients. Controlled clinical trials are needed to confirm our preliminary results. Disclosures: No relevant conflicts of interest to declare.

Bortezomib Added to the Standard Mobilization Regimen of G-CSF and High-Dose Cyclophosphamide Is a Safe and Effective Combination for a High Yield Stem Cell Collection While Promoting Further Tumor Mass Reduction in Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2953-2953 ◽  
Author(s):  
Jessica L. Stern ◽  
Brian Di Carlo ◽  
Michael W. Schuster ◽  
Tsiporah B. Shore ◽  
John G. Harpel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Alkylating Agents ◽  
Pegylated Liposomal Doxorubicin ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Cell Mobilization ◽  
Grade 3 ◽  
Stem Cell Collection

Abstract Standard stem cell mobilization regimens for multiple myeloma patients include G-CSF alone or in combination with high dose cyclophosphamide. Given the known in vitro and in vivo synergy between alkylating agents and proteosome inhibitors, we sought to optimize the potential for concurrent cytoreduction by adding bortezomib to the mobilization regimen. Five evaluable patients, whose prior therapy consisted of six cycles of a 21-day treatment with bortezomib/dexamethasone +/− pegylated liposomal doxorubicin, were mobilized. They received IV push bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 in combination with high-dose cyclophosphamide at 3mg/m2 and MESNA on day 8. G-CSF was given for 10 consecutive days starting on day 9. One patient began this regimen in nCR, two were in PR, and two were in CR by urine and serum immunofixation and bone marrow evaluation. Stem cells were easily harvested from each of the five patients. The number of CD34+ cells collected far exceeded the amount normally mobilized with cyclophosphamide and/or G-CSF alone, with four out of 5 patients collected in a single day. The two patients who began the mobilization cycle in PR continued to respond positively. Their protein levels dropped an additional 8.9 and 14.6 percent respectively during the last cycle. The patient who began mobilization in nCR achieved a CR by the end of treatment. Some expected toxicities associated with high dose cyclophosphamide and G-CSF occurred. All patients experienced grade 3 and 4 cytopenias, however, they recovered and were able to continue on to transplant. Serious adverse events of grade 3 chest pain (non-cardiac), grade 4 pneumonia, and grade 4 febrile neutropenia also occurred. Bortezomib in addition to high dose cyclophosphamide followed by G-CSF is a novel, well-tolerated and efficacious combination for stem cell mobilization in patients with multiple myeloma. This regimen not only yields a high number of stem cells within a short collection time, but may further cytoreduce disease as well. Stem Cell Collection Patients Days Required for Collection CD34+ Stem Cells (million/kg) 1 1 21.2 2 1 47.4 3 1 22 4 1 17.9 5 4 40.6

The Effect of Bortezomib (B) Alone or in Combination with Other Agents for Stem Cell Mobilization in Mice

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 583-583
Author(s):  
Armin Ghobadi ◽  
Matthew Holt ◽  
Julie Ritchey ◽  
John F. DiPersio
Keyword(s):  
Stem Cell ◽  
Conflicts Of Interest ◽  
Group Versus ◽  
Fold Increase ◽  
Stem Cell Mobilization ◽  
Control Group ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Cell Mobilization ◽  
Phosphate Buffered Saline

Abstract Abstract 583 Introduction: Granulocyte colony-stimulating factor (G-CSF) is the most commonly used drug for stem cell mobilization. Unfortunately, 5–30% of patients fail to collect sufficient hematopoietic stem/progenitor cells (HSPCs) necessary for transplant. New strategies are needed to increase HSPCs collection in these patients. Apart from cytotoxic effect, bortezomib decreases expression of cell adhesion molecules including VCAM-1. Therefore, we hypothesize that bortezomib can mobilize HSPCs. Method: C57BL/6 (B6) mice were injected with intravenous (IV) bortezomib (0.8 mg/kg) or Phosphate buffered saline (PBS). Blood were harvested at baseline and 12, 15, 18, 21, and 24 hours (h) after injections and plated on MethoCult media (StemCell Technologies). For evaluation of mechanism and source of mobilized HSPCs, bortezomib versus PBS experiments were performed in splenectomized B6 mice and VLA4 knockout (VLA4KO) mice in addition to B6 mice. Experiments involving combination of bortezomib with G-CSF, AMD3100, and Cytoxan were also conducted in B6 mice. In bortezomib-G-CSF group (BG), bortezomib was given on day1 and G-CSF (250 μg/kg subcutaneously) was given on days 2, 3, 4, and 5. In G-CSF-bortezomib group (GB), G-CSF was given on days 2, 3, 4, and 5 and bortezomib was given on day 5. G-CSF (G) control group received G-CSF on days 2, 3, 4, and 5. In bortezomib-AMD3100 group (BA), bortezomib was given at baseline and AMD3100 (5 mg/kg subcutaneously) was given 15 h after bortezomib. In PBS-AMD3100 control group (PA), bortezomib at baseline in BA group was substituted with PBS. In cyclophosphamide-G-CSF group (CG), cyclophosphamide (200 mg/kg intraperitoneal) was given at baseline and G-CSF was given on days 2, 3, 4, and 5. In cyclophosphamide-bortezomib-G-CSF group (CBG), bortezomib at baseline was added to CG experiment. Results: Bortezomib compared with PBS in B6 mice resulted in a significantly higher CFU-C 12 h to 18 h after baseline injections (mean peak CFU-C: 680/ml vs. 100/ml respectively, fold increase in CFU-C: 6.8 vs. 0.8 respectively, P = 0.0002) (Figure 1). In bortezomib group, CFU-C remained at peak from 12 h to 18 h and returned close to baseline 24 h after bortezomib. White blood cell (WBC) peak of 1.5 fold over baseline was observed 12 h to 15 h after bortezomib. There was no statistically significant difference in bortezomib HSPC mobilization in non-splenectomized vs. splenectomized mice (mean peak of 580/ml vs. 550/ml respectively, P = 0.89). In VLA4KO experiments, there was no statistically significant difference in peak CFU-C in bortezomib group versus PBS group (mean 730/ml vs. 590/ml respectively, P = 0.18) suggesting no HSPC mobilization effect for bortezomib in VLA4KO mice (Figure 2). In bortezomib plus G-CSF (BG) experiments, peak CFU-C on day 6 in BG group was significantly higher than G-CSF group (mean peak CFU-C: 4700/ml vs. 2400/ml respectively, P = 0.005). In G-CSF plus bortezomib (GB) experiments, peak CFU-C on day 6 in GB group was significantly higher than G-CSF group (mean peak CFU-C: 5600/ml vs. 2400/ml respectively, P = 0.001). There was no statistically significant difference in peak CFU-C in BG vs. GB groups (P = 0.28). In bortezomib plus AMD3100 (BA) vs. PBS plus AMD3100 (PA) experiments, peak CFU-C 3 h after AMD3100 in BA group was significantly higher than PA group (peak CFU-C: 2600/ml vs. 1100/ml respectively, fold increase in CFU-C: 105 vs. 12.5 respectively, P = 0.01) (Figure 3). In cyclophosphamide-G-CSF (CG) vs. cyclophosphamide-bortezomib-G-CSF (CBG) chemomobilization experiments, CBG compared to CG resulted in a trend toward higher CFU-C peak on day 6 (23500/ml vs. 21000/ml respectively, P = 0.49) and higher CFU-C on day 7 (14200/ml vs. 8700/ml respectively, P = 0.03). Conclusion: Bortezomib is a potent HSPC mobilizer drug, augment AMD3100 and G-CSF mobilization in at least an additive fashion, and increase and extend chemomobization effect of cyclophosphamide. Bortezomib mobilization mechanism probably involves VLA4/VCAM-1 axis. Bone marrow rather than spleen is the source of HSPC's mobilized by bortezomib. Disclosures: No relevant conflicts of interest to declare.

How do stem cells find their way home?

Blood ◽  
2005 ◽  
Vol 106 (6) ◽  
pp. 1901-1910 ◽  
Author(s):  
Tsvee Lapidot ◽  
Ayelet Dar ◽  
Orit Kollet
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Lymphocyte Function ◽  
Hematopoietic Stem ◽  
Stem Cell Homing ◽  
Late Antigen ◽  
Multistep Process ◽  
Cell Mobilization ◽  
Membrane Type

AbstractMigration of hematopoietic stem cells through the blood, across the endothelial vasculature to different organs and to their bone marrow (BM) niches, requires active navigation, a process termed homing. Homing is a rapid process and is the first and essential step in clinical stem cell transplantation. Similarly, homing is required for seeding of the fetal BM by hematopoietic progenitors during development. Homing has physiological roles in adult BM homeostasis, which are amplified during stress-induced recruitment of leukocytes from the BM reservoir and during stem cell mobilization, as part of host defense and repair. Homing is thought to be a coordinated, multistep process, which involves signaling by stromal-derived factor 1 (SDF-1) and stem cell factor (SCF), activation of lymphocyte function–associated antigen 1 (LFA-1), very late antigen 4/5 (VLA-4/5) and CD44, cytoskeleton rearrangement, membrane type 1 (MT1)–matrix metalloproteinase (MMP) activation and secretion of MMP2/9. Rolling and firm adhesion of progenitors to endothelial cells in small marrow sinusoids under blood flow is followed by trans-endothelial migration across the physical endothelium/extracellular matrix (ECM) barrier. Stem cells finalize their homing uniquely, by selective access and anchorage to their specialized niches in the extravascular space of the endosteum region and in periarterial sites. This review is focused on mechanisms and key regulators of human stem cell homing to the BM in experimental animal models and clinical transplantation protocols.

scholarly journals Stem Cells from the Apical Papilla: A Promising Source for Stem Cell-Based Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Jun Kang ◽  
Wenguo Fan ◽  
Qianyi Deng ◽  
Hongwen He ◽  
Fang Huang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Current Knowledge ◽  
Embryonic Stem ◽  
Permanent Teeth ◽  
Promising Alternative ◽  
Dental Tissues ◽  
Cell Based Therapy ◽  
Apical Papilla ◽  
Promising Source

Stem cells are biological cells that can self-renew and can differentiate into multiple cell lineages. Stem cell-based therapy is emerging as a promising alternative therapeutic option for various disorders. Mesenchymal stem cells (MSCs) are multipotent adult stem cells that are isolated from various tissues and can be used as an alternative to embryonic stem cells. Stem cells from the apical papilla (SCAPs) are a novel population of MSCs residing in the apical papilla of immature permanent teeth. SCAPs present the characteristics of expression of MSCs markers, self-renewal, proliferation, migration, differentiation, and immunosuppression, which support the application of SCAPs in stem cell-based therapy, including the immunotherapy and the regeneration of dental tissues, bone, neural, and vascular tissues. In view of these properties and therapeutic potential, SCAPs can be considered as promising candidates for stem cell-based therapy. Thus the aim of our review was to summarize the current knowledge of SCAPs considering isolation, characterization, and multilineage differentiation. The prospects for their use in stem cell-based therapy were also discussed.

Incorporation of Posttransplant Cyclophosphamide (PCy) As Part of Standard Immunoprophylaxis (IP) for All Allogeneic Transplants: A Retrospective, Single Institution Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4485-4485
Author(s):  
Dennis Cooper ◽  
Jackie Manago ◽  
Vimal Patel ◽  
Dale Schaar ◽  
Tracy Krimmel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Transplantation ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Risk Index ◽  
Chronic Gvhd ◽  
Number Of Patients ◽  
One Year ◽  
Disease Free

Background: The incorporation of PCy in IP has allowed transplantation of stem cells from haploidentical (HI) family members such that nearly all patients have a potential donor. Thus far, HI stem cell transplantation with PCy appears to yield comparable results to matched unrelated (MUD) and matched sibling donors (MSD) who have been treated with conventional GVHD regimens, but with less chronic GVHD (cGVHD). Particularly in light of the low incidence of cGVHD, which has not been achieved with other IP strategies after T cell-replete products, PCy is being investigated after MUD and MSD transplantation where complications from cGVHD remain the major cause of non-relapse mortality. A recent study from the BMTCTN showed that in patients conditioned with reduced intensity regimens and who received MSD and MUD stem cells, the addition of PCy to standard IP (SIP) was superior to either bortezomib or maravoric in the composite endpoint of graft-versus-host disease-free, relapse-free survival (GRFS). However, this study did not include patients who received ablative conditioning regimens and did not report on the percentage of patients who were disease-free and off immunosuppression (DFOI) at 1 year after transplant. In the present study, we have compared our experience with the addition of PCy for essentially all allogeneic stem cell transplants treated over a 2 year period with the results of patients treated with SIP in the prior two year span. Outcomes of interest included one-year overall survival (OS) and one-year GRFS as well as the percentage of patients DFOI at one year. Methods: With the exception of patients receiving umbilical cord blood transplants, beginning in April 2016, all but two patients who received allogeneic transplants were given mobilized peripheral blood stem cells and then treated with PCy on days +3 and +4 followed by tacrolimus and mycophenolate on day 5. In the absence of GVHD, mycophenolate was stopped at days +35-50 and tacrolimus was tapered beginning after day +100 unless there was low donor chimerism or a suspicion of relapse in which case tacrolimus could be tapered sooner. In order to have at least one-year follow-up, the last patient included in the study was treated before April 2018. During this time period, MSD were prioritized over MUD which in turn were chosen over haploidentical donors. For comparison, we looked at the prior 2 year period (2014-2016) in which patients were treated with SIP (including ATG in patients who received MUD stem cells). Because of a higher percentage of patients with an advanced disease risk index (DRI) in the years 2014-2016, we restricted our analysis in the SIP cohort to those patients with low and intermediate risk disease but included all patients in the more recent period who received PCy. Results: There were 68 patients treated in the PCy group, including 2 patients who received PCy after HI transplants in the years 2014 and 2015. After eliminating patients with high DRI there were 40 patients in the earlier SIP cohort of patients. The resulting patient groups were similar with respect to median age (53) and diagnosis (approximately 80% of patients with AML and ALL). There was a slightly higher percentage of patients in the SIP group with hematopoietic cell transplantation-comorbidity index scores of 3 or more (52.5 vs 48.5). In the PCy group the number of patients with early, intermediate and advanced DRI were 2, 53 and 13, whereas in the (modified) SIP category 2 patients had a low DRI and 38 had intermediate DRI. In the PCy group, HI donors comprised 26.5% of the total compared to 19.1% MSD and 54.4% MUD donors. In the SIP group, MSD and MUD donors accounted for 30% and 70% of the donors. One-year percentages of OS, GRFS and DFOI were 79.4, 47.1 and 44.1 in the PCy group compared to 72, 45 and 35 in the SIP cohort. If the analysis of the PCy group is limited to the 50 patients with MSD and MUD donors (as in the SIP cohort), the one-year OS, GRFS and DFOI are 88, 52 and 52. Conclusions: PCy in combination with SIP resulted in at least comparable results as SIP despite the inclusion of 19% of patients with a high DRI and 26.5% HI donors. The results with the addition of PCy are excellent in patients with MSD and MUD donors with more than half of the patients GRFS and DFOI at one year. Future studies on GVHD prophylaxis should report DFOI as the latter status may be the best platform for posttransplant strategies aimed at eliminating minimal residual disease and for improving QOL. Disclosures No relevant conflicts of interest to declare.

Differential Role for VLA-5 in Mobilization of Heamotopoieic Stem Cells Toward Peripheral Blood and Homing to Bone Marrow and Spleen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2190-2190 ◽  
Author(s):  
Pieter K. Wierenga ◽  
Ellen Weersing ◽  
Bert Dontje ◽  
Gerald de Haan ◽  
Ronald P. van Os
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Hematopoietic Stem ◽  
Late Antigen ◽  
Cell Mobilization

Abstract Adhesion molecules have been implicated in the interactions of hematopoietic stem and progenitor cells with the bone marrow extracellular matrix and stromal cells. In this study we examined the role of very late antigen-5 (VLA-5) in the process of stem cell mobilization and homing after stem cell transplantation. In normal bone marrow (BM) from CBA/H mice 79±3 % of the cells in the lineage negative fraction express VLA-5. After mobilization with cyclophosphamide/G-CSF, the number of VLA-5 expressing cells in mobilized peripheral blood cells (MPB) decreases to 36±4%. The lineage negative fraction of MPB cells migrating in vitro towards SDF-1α (M-MPB) demonstrated a further decrease to 3±1% of VLA-5 expressing cells. These data are suggestive for a downregulation of VLA-5 on hematopoietic cells during mobilization. Next, MPB cells were labelled with PKH67-GL and transplanted in lethally irradiated recipients. Three hours after transplantation an increase in VLA-5 expressing cells was observed which remained stable until 24 hours post-transplant. When MPB cells were used the percentage PKH-67GL+ Lin− VLA-5+ cells increased from 36% to 88±4%. In the case of M-MPB cells the number increased from 3% to 33±5%. Although the increase might implicate an upregulation of VLA-5, we could not exclude selective homing of VLA-5+ cells as a possible explanation. Moreover, we determined the percentage of VLA-5 expressing cells immediately after transplantation in the peripheral blood of the recipients and were not able to observe any increase in VLA-5+ cells in the first three hours post-tranpslant. Finally, we separated the MPB cells in VLA-5+ and VLA-5− cells and plated these cells out in clonogenic assays for progenitor (CFU-GM) and stem cells (CAFC-day35). It could be demonstared that 98.8±0.5% of the progenitor cells and 99.4±0.7% of the stem cells were present in the VLA-5+ fraction. Hence, VLA-5 is not downregulated during the process of mobilization and the observed increase in VLA-5 expressing cells after transplantation is indeed caused by selective homing of VLA-5+ cells. To shed more light on the role of VLA-5 in the process of homing, BM and MPB cells were treated with an antibody to VLA-5. After VLA-5 blocking of MPB cells an inhibition of 59±7% in the homing of progenitor cells in bone marrow could be found, whereas homing of these subsets in the spleen of the recipients was only inhibited by 11±4%. For BM cells an inhibition of 60±12% in the bone marrow was observed. Homing of BM cells in the spleen was not affected at all after VLA-5 blocking. Based on these data we conclude that mobilization of hematopoietic progenitor/stem cells does not coincide with a downregulation of VLA-5. The observed increase in VLA-5 expressing cells after transplantation is caused by preferential homing of VLA-5+ cells. Homing of progenitor/stem cells to the bone marrow after transplantation apparantly requires adhesion interactions that can be inhibited by blocking VLA-5 expression. Homing to the spleen seems to be independent of VLA-5 expression. These data are indicative for different adhesive pathways in the process of homing to bone marrow or spleen.

A Prospective Phase II Comparison of Stem Cell Source Using Rituximab, Ifosfamide, Carboplatin, Etoposide (RICE) RE—Induction, Then High Dose Fludarabine, Busulfan (FLUBU) and Autologous (ASCT) or Allogeneic (AlloSCT) Hematopoietic Blood Stem Cell Transplantation for Mantle Cell (MCL) and Relapsed Low-Grade B-Cell Non-Hodgkin’s Lymphoma (NHL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 915-915
Author(s):  
Douglas A. Stewart ◽  
Michael Voralia ◽  
Ahsan Chaudhry ◽  
Oluyemi Jeje ◽  
Donald Morris ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Phase Ii ◽  
Blood Stem Cell ◽  
High Dose ◽  
Free Survival ◽  
Stem Cell Source ◽  
Cell Source ◽  
Prospective Phase ◽  
Grade 3

Abstract Introduction: A “genetically-randomized” prospective phase II study was designed to compare stem cell source following novel, uniform, and expected low toxicity re-induction and high dose chemotherapy for indolent B-cell NHL. Patients and Methods: Pts with MCL in 1st remission or 1st relapse, or other indolent B-cell lymphoma in 1st or 2nd relapse were eligible providing adequate organ function and age <65 years. Pts received RICE (Rituximab 375mg/m2 d1,8,15,22, Ifosfamide 1.67g/m2 d16-18, Carboplatin AUC=5 d17, Etoposide 100mg/m2 d16-18), with G-CSF d22-30, and apheresis d29-31 if ASCT, then FluBu (Fludarabine 50mg/m² d-6to-2, Busulfan 3.2 mg/kg IV daily d-5to-2) and SCT d0. GVHD prophylaxis for AlloSCT involved ATG 4.5mg/kg, MTX and CSA. Results: The initial 43 pts accrued from 06/2001-03/2004 included Follicular=30, MCL=7, SLL=4, other histology=2. Disease status was 1st remission=2, 1st relapse=18, 2nd relapse=12, 10 refractory=11. The median EFS following most recent prior chemotherapy was 7 mos. RICE resulted in an overall RR of 72%. Blood stem cell source was ASCT=27, donor SCT=16 (related=14, unrelated=1, syngeneic=1). For ASCT, a median of 5.9 (1–14.5) x106 CD34+ cells/kg were collected from 1 (n=17) or 2 (n=10) 15-25L aphereses. Three pts required a second mobilization procedure. 16/24 pts converted from positive to negative marrow biopsies post-RICE. Two pts had NHL detected in the autograft. FluBu resulted in no acute Bearman grade 3-4 RRT(overall 100d non-relapse mortality (NRM)=0% for both ASCT and donor SCT). Median engraftment times were slightly longer post AlloSCT than ASCT (ANC>0.5 = 15 vs 11d, and platelets>20 = 12 vs 9d, respectively). Of 15 AlloSCT pts, grade 3–4 aGVHD occurred in 5 (33%), cGVHD occurred in 64%, and death from extensive cGVHD + infection occurred in 5 pts from 7-13mo post-AlloSCT (overall NRM=33% for AlloSCT). With a median follow-up of 22mo, the 2 year projected outcome of ASCT vs Allo/Syngeneic-SCT for relapse-free survival (RFS) was 64% vs 87% (logrank p=0.48), event-free survival (EFS) 63% vs 52% (logrank p=0.38), and overall survival (OS) 86% vs 46% (logrank p=0.0018), respectively. For relapsed follicular lymphoma only, the 2yr EFS was 61% vs 59% (logrank p=0.49) and OS 100% vs 51% (logrank p=0.0009) for ASCT (n=19) vs Allo/Syngeneic SCT (n=11), respectively. Conclusion: These preliminary results suggest that RICE can "in-vivo" purge autografts but mobilizes blood stem cells only moderately well. RICE-FluBu/ASCT may result in prolonged EFS with significantly less NRM than AlloSCT.

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