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

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

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

Phase III Randomized Stem Cell Mobilization Trial Comparing Standard Vs Double-Dose G-CSF Vs Standard Doses of G-CSF Plus GM-CSF in Hard to Mobilize Patients Undergoing An Autologous Hematopoietic Stem Cell Transplant (HSCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3228-3228
Author(s):  
Elizabeth Berger ◽  
Christopher Seet ◽  
Mala Parthasarathy ◽  
Tulio Rodriguez ◽  
Scott E. Smith ◽  
...  
Keyword(s):  
Stem Cell ◽  
Standard Dose ◽  
Stem Cell Mobilization ◽  
Phase Iii ◽  
Control Group ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Cell Mobilization

Abstract Abstract 3228 Poster Board III-165 Introduction Using standard dose G-CSF (10 μg/kg) for stem cell mobilization, 25-40% of patients, deemed to be hard to mobilize based on prior therapy, will not collect sufficient HSC (> 2-2.5 × 106 CD34/kg) to proceed to a prompt autotransplant. Strategies to improve CD34/kg yields have included dose escalating G-CSF up to 30 μg/kg or combining G-CSF and GM-CSF. While dose escalated G-CSF is effective in increasing CD34 yields in normal donors as is the combination of G-CSF and GM-CSF, their comparative value in pre-treated patients has not been tested. To determine the value of these strategies, we performed a randomized comparison of high dose G-CSF (30 μg/kg as 2 doses 12 hours apart), to the combination of simultaneous single daily doses of G-CSF (10 μg/kg) plus GM-CSF (5 μg/kg), to a control group receiving G-CSF at an equivalent total dose of cytokine to the combination arm (15μg/kg) as a single dose. Patients and Methods Patients were eligible if heavily pre-treated, defined as: a minimum of 10 total cycles of combination chemotherapy and two prior regimens, or a total of 6 chemotherapy cycles if the patient also received RT to marrow bearing sites, platinum-based chemotherapy or 2 or more cycles of any BCNU or fludarabine containing regimen. Baseline WBC had to be > 3000/μl, ANC > 1500/μl and a platelets > 100,000/μl. Twelve liter aphereses began on day 5 of mobilization, and continued until ≥ 4 × 106 CD34/kg were collected or a maximum of 5 aphereses. Patients typically proceeded to transplant if they had ≥ 2.5 × 106 CD34/kg collected and were always re-mobilized if they collected < 2.0 × 106 CD34/kg. CD34 subsets (CD34+/CD33- and CD34+/CD38-) were also assessed for the 3 groups to determine if more primitive HSC were mobilized by the 2 novel strategies. The sample size was calculated based as follows: 60% of the control group would collect 2.5 × 106 CD34/kg and this would rise to 90% in one or both study arms. The detection of such differences with a power of 80% and a 2-sided alpha level of 0.025 required a total sample of 120 patients. Results A total of 120 patients were randomized; 119 were eligible. Patient demographics, shown in the Table, were matched among the three groups: The % of patients collecting ≥2.5 × 106 CD34/kg was: standard G: 60%, high dose G: 57% (p = 1.0), G + GM: 41% (p = 0.1). Median CD34 collected in first mobilization were, 3.6 × 106/kg, 3.0 × 106/kg (p = 0.22) and 2.0 × 106/kg (p = 0.05) respectively in a median of 4, 4, and 5 aphereses (p = NS). Re-mobilization rates: standard G; 37.5%, high dose G: 35%; G + GM: 50% (p = NS). Total median CD34 collected from first and any second mobilizations were: standard G: 4.8 × 106/kg, high dose G: 3.9 × 106/kg, and G + GM: 3.5 × 106/kg. One patient in the standard G arm and 3 in high dose G did not proceed to transplant due to poor initial mobilization and progression in 2, and one each for progression or poor mobilization alone. There were no significant differences in median engraftment times: for ANC, 10, 11 and 15 days respectively for the standard G-, high dose G- and G + GM arms and for platelets, 11, 13 and 14 days respectively. The overall survivals @ the median f/u time of 37 months were 59.8%, 61.8% and 48.1% respectively (p = 0.272) for the three groups. The % primitive HSC (CD34+/CD33- and CD34+/CD38-) from the first mobilization were identical in the 3 patient groups. Conclusions We found no advantage to dose escalated G-CSF nor to the combination of G-CSF and GM-CSF to mobilize HSC for autotransplantation in heavily pre-treated patients. We also did not find higher numbers of more primitive CD34 subsets mobilized by these newer strategies. Alternative approaches, e.g. the combination of plerixifor + standard dose G-CSF (Stiff et al: BBMT; 15:249-56, 2009) would appear to be the preferred method of initial HSC mobilization for heavily pre-treated patients. Disclosures Stiff: Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Exercise as an Adjuvant Therapy for Hematopoietic Stem Cell Mobilization

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Russell Emmons ◽  
Grace M. Niemiro ◽  
Michael De Lisio
Keyword(s):  
Stem Cell ◽  
Adjuvant Therapy ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
Cell Transplant ◽  
Pharmacological Agents ◽  
Hematopoietic Stem ◽  
Hematopoietic Stem Cell Mobilization ◽  
Cell Mobilization ◽  
Exercise Induced

Hematopoietic stem cell transplant (HSCT) using mobilized peripheral blood hematopoietic stem cells (HSPCs) is the only curative strategy for many patients suffering from hematological malignancies. HSPC collection protocols rely on pharmacological agents to mobilize HSPCs to peripheral blood. Limitations including variable donor responses and long dosing protocols merit further investigations into adjuvant therapies to enhance the efficiency of HSPCs collection. Exercise, a safe and feasible intervention in patients undergoing HSCT, has been previously shown to robustly stimulate HSPC mobilization from the bone marrow. Exercise-induced HSPC mobilization is transient limiting its current clinical potential. Thus, a deeper investigation of the mechanisms responsible for exercise-induced HSPC mobilization and the factors responsible for removal of HSPCs from circulation following exercise is warranted. The present review will describe current research on exercise and HSPC mobilization, outline the potential mechanisms responsible for exercise-induced HSPC mobilization, and highlight potential sites for HSPC homing following exercise. We also outline current barriers to the implementation of exercise as an adjuvant therapy for HSPC mobilization and suggest potential strategies to overcome these barriers.

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.

scholarly journals Ixazomib, an Oral Proteasome Inhibitor, Induces Rapid Mobilization of Hematopoietic Stem Cells in Mice

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 513-513 ◽  
Author(s):  
Armin Ghobadi ◽  
Michael P. Rettig ◽  
Matthew Holt ◽  
Julie Ritchey ◽  
Linda Eissenberg ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Proteasome Inhibitor ◽  
Stem Cell Mobilization ◽  
Oral Gavage ◽  
Hematopoietic Stem ◽  
Colony Forming Unit ◽  
Significant Difference ◽  
Unit Cells ◽  
Cell Mobilization

Abstract 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) to proceed to transplant. New strategies are needed to increase HSPCs collection in these patients. We previously reported that bortezomib directly and rapidly mobilizes HSPCs in mice by modulating the VLA-4/VCAM-1 axis (Ghobadi A et al. Blood 2014, 124: 2742-2753). Ixazomib (MLN9708) is a next-generation small-molecule proteasome inhibitor that has several potential advantages over bortezomib including oral route of administration. Here we study the effect of ixazomib on stem cell mobilization in mice. Methods: DBA mice were treated with: (1) ixazomib via oral gavage (o.g., 8 mg/kg), (2) a single intravenous (iv) dose of bortezomib (0.8 mg/kg), (3) AMD3100 (5 mg/kg) SC, and (4) control diluent for ixazomib (2-hydroxypropyl-β-cyclodextrin [HPBCD]). Blood was harvested at baseline and 12, 15, and 24 hours (h) after ixazomib and bortezomib administration and at 3 hours and 12 hours after AMD3100 administration. Harvested peripheral blood (PB) was plated on MethoCult media (Stem Cell Technologies) for colony forming unit-cells (CFU-C) enumeration. Results: Compared to vehicle (ixazomib diluent, 2-hydroxypropyl-β-cyclodextrin [HPBCD]), ixazomib mobilized significantly more peripheral blood colony forming unit-cells (CFU-C) at 12 - 15 h after administration (mean peak CFU-C: 105/ml vs. 870/ml respectively, i.e., a 0.6 vs. 5-fold increase in CFU-C , P < 0.02; Figure 1A). The majority of CFU-Cs mobilized by ixazomib were CFU-GM (CFU-granulocyte and monocyte, Figure 1B). The magnitude and kinetics of HSPC mobilization in the single ixazomib oral gavage group was identical to a single dose of IV bortezomib (Figure 1C, mean peak of 870/ml vs. 975/ml respectively, P > 0.66). There was no statistically significant difference in peak HSPC mobilization between the ixazomib (12 h after ixazomib administration) and AMD3100 groups (3 h after AMD3100 administration) (mean peak of 870/ml vs. 1240/ml respectively, P = 0.36) suggesting that ixazomib is a potent HSPC mobilizing agent (Figure 1D) with intermediate mobilization kinetics compared to AMD3100 (2-3 hours) and G-CSF (5-6 days) and with identical kinetics to IV bortezomib (12-15 hours). Conclusion: Ixazomib is a potent and modestly rapid HSPC mobilizer agent in mice. Kinetics and magnitude of HSPC mobilization by ixazomib is identical to bortezomib. Trials to assess proteasome inhibitors as mobilizing agents are currently underway at Washington University. Disclosures No relevant conflicts of interest to declare.

Outcomes of tbo-filgrastim, filgrastim-sndz or filgrastim for mobilization in patients undergoing an autologous hematopoietic stem cell transplant: A single center experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19000-e19000
Author(s):  
Klodiana Neme ◽  
David Henkin ◽  
Nancy Mikulandric ◽  
Meredith Grycki ◽  
Angela Michael ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Stem Cell Mobilization ◽  
Hospital Length Of Stay ◽  
Cell Transplant ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Cell Mobilization

e19000 Background: Studies have reported that use of filgrastim (G) or any biosimilar result in similar stem cell yield during hematopoietic stem cell mobilization, but little is known on the effect of these biosimilars on length of hospitalization for the transplant procedure, engraftment, and long term survival of autologous hematopoietic stem cell transplant (HSCT) patients. Beginning January 2017, the Henry Ford Cancer Institute (HFCI) began utilizing tbo-filgrastim (TBO) and filgrastim-sndz (SNDZ) as part of mobilization. This study was conducted to evaluate transplant specific outcomes in HSCT patients comparing biosimilar and reference filgrastim products. Methods: This study retrospectively evaluated all patients treated at HFCI who received G-CSF based mobilization for HSCT between 1/2017 and 11/2018. Patient-, mobilization- and transplant specific variables were collected and analyzed. Results: A total of 113 patients underwent stem cell mobilization followed by collection and autologous HSCT. Of the 73 patients analyzed, 62% had a diagnosis of Multiple Myeloma (MM), 22% had Non-Hodgkin Lymphoma (NHL). Approximately 45% of patients received TBO, 44% received G and remainder received SNDZ. The percentage of patients who proceeded to HSCT was 86%. There was no difference in adequate CD34+ yield among the three G-CSF products (P = 0.074). There was no difference in mobilization associated complications including bone pain and thrombocytopenia. Plerixafor use was similar among the groups (P = 0.55). Actual CD34+ (P = 0.31) and the number of apheresis sessions required to collect an adequate CD34+ yield (P = 0.30) were not different among the groups. No significant differences were noted in time to neutrophil (P = 0.96) or platelet engraftment (P = 0.91) and hospital length of stay (P = 0.78). We found similar rates of infection, febrile neutropenia, and mucositis among the three groups. Relapse rates were also similar among the groups. Conclusions: In our institution transplant related outcomes were similar among patients who received TBO, SNDZ, and G as part of their pre-transplant mobilization protocol.

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