Rapid Mobilization Of CD34+ Progenitor Cells With TG0054-03, a novel CXC Chemokine Receptor 4 (CXCR4) Antagonoist

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 905-905 ◽  
Author(s):  
Michael W. Schuster ◽  
Nabil Hagog ◽  
Bita Jalilizeinali ◽  
Sharon Funkhauser ◽  
Mary Sophy Yohannan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Chemokine Receptor ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Single Agent ◽  
Platelet Recovery ◽  
Cd34 Cells ◽  
Stem Cell Collection ◽  
Historical Controls

Abstract Background TG-0054 (burixafor) is a potent and specific antagonist of the human CXCR4 chemokine receptor. TG-0054 blocks the interaction between CXCR4 and stromal cell-derived factor-1 (SDF-1), thus causing a rapid mobilization of stem cells from the bone marrow into peripheral blood within 1-3 hours of intravenous administration of the drug. Materials and Methods: An early phase II trial was conducted in patients with multiple myeloma (MM), non-Hodgkin lymphoma (NHL) or Hodgkin disease (HD) to evaluate the safety and stem cell mobilization of TG-0054 alone or in combination with G-CSF. 12 patients (1 HL, 7 MM, and 4 NHL patients) received an i.v. dose of 3.14 mg/kg TG-0054, and peripheral blood CD34 counts were assessed at 2, 4 and 6 hours post drug infusion. Patients who achieved at least 10 CD34 cell/ul in the peripheral blood were collected by large volume leukapheresis (24L) for 1-4 days to obtain a predetermined target of >2.5 x 106 CD34 cells /kg. Results: Seven patients (1 HD, 6 MM) were successfully mobilized with TG-0054 as a single agent achieving a cumulative CD34+ stem cell collection of 4.0 to 10.4 x106 cells /kg over 2-4 leukapheresis sessions. Patients who failed to mobilize with TG0054 as a single agent on day +1 were placed on the second arm of the study, where they received 5 doses of granulocyte colony stimulating factor (G-CSF) at a dose of 10 ug/kg beginning on day +4 with TG-0054added back in combination on day +8. These remaining five patients (1 MM, 4 NHL) who did not mobilize with TG0054 alone on day +1 and received G-CSF plus TG-0054 were leukapheresed on day +8. Those patients achieved a cumulative CD34 peripheral blood stem cell collection of of 3.2-21.0 x106 cells /kg over 1-4 leukaphereses sessions. Conclusion: TG-0054 exhibited potent and rapid mobilization of CD34+ stem cells, with favorable safety profile in patients. Engraftment All 12 patients received conditioning regimens (BEAM for the lymphoma patients and melphalan for the myeloma patients) followed by a stem cell infusion of at least 3.0 x106 CD34+ cells/kg. All patients engrafted without delay compared to historical controls. Median days to WBC engraftment were 12. Median days to platelet recovery of 20,000 and 50,000 were 20 and 20.5 days, respectively. Engraftment results of TG-0054 mobilized patients are similar to those seen in a matched group of historical controls. We have observed that mobilization with TG-0054 caused a preferential mobilization of mononuclear cells (MNC) component of the graft. Percent MNC in TG-0054 mobilized patients‘ grafts were 78.9+15.2 (median 81.5) as compared to percent of MNC in G-CSF mobilized patients‘ grafts of 62.6+27.7 (median 69.6). Disclosures: Schuster: TaiGen Biotechnology Co., Ltd: Research Funding. Tsai:TaiGen Biotechnology Co., Ltd: Employment. Hsu:TaiGen Biotechnology Co., Ltd: Employment, Equity Ownership. Chang:TaiGen Biotechnology Co., Ltd: Employment. Hsu:TaiGen Biotechnology Co., Ltd: Employment.

Chemotherapy Combined with Granulocyte Colony Stimulating Factor (G-CSF) for Mobilization of CD34+ Cells in Lymphoma and Multiple Myeloma Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5441-5441
Author(s):  
Gaofeng Zheng ◽  
Yanlong Zheng ◽  
Yi Luo ◽  
Jimin Shi ◽  
Weiyan Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Success Rate ◽  
Peripheral Blood ◽  
Hodgkin's Lymphoma ◽  
Collection Rate ◽  
Cd34 Cells ◽  
Stem Cell Collection ◽  
The Ideal

Abstract Objective: To investigate and analyze factors which effect autologous stem cell collection in patients with lymphoma and multiple myeloma (MM) during chemotherapy combined with G-CSF mobilization, for improving quality and effectiveness of autologous stem cell transplantation. Methods: A retrospective analysis was performed from April 1, 2006 to October 31, 2013 in our hospital and 128 lymphoma and MM patients whose autologous peripheral blood stem cells (PBSCs) were collected including 75 patients with malignant lymphoma,7 cases of Hodgkin's lymphoma and 68 non-Hodgkin's lymphoma (NHL) cases as well as 53 MM patients were enrolled. The stem cells of all patients were mobilized by chemotherapy combined with G-CSF and collected via a continuous flow cell separation instrument (COBE Spectra, Lakewood, CO). Mobilize failure was defined when the amount of CD34 + cells was less than 2.0 x 106 / kg, whereas ≥2.0 * 106 / kg was defined as successful mobilization. More than 5.0x 106 cells / kg or more was considrered as ideal mobilization. Univariate and multivariate regression analyses of factors for mobilization failure, successful mobilization and ideal mobilization acquisition were performed. Results: There were more CD34+ cells in MM patients than in lymphoma patients (P = 0.064). The collection rates of CD34 + cells in MM patients were ≥ 2.0 x106 / kg in 64.8% (83 cases) and ≥ 5.0 x 106 / kg in 35.2% (45 cases). MM patients with a success collection ratio was 73.6 % (39/53) and the ideal collection rate was 43.4% (23/53), which was higher than in the NHL group with a success rate and ideal rate of 58.7% (44/75) and 30.7% (23/75). A total of 35.2 % (45 cases, including 31MM cases and 14 lymphoma cases) a mobilization was not successful. Conclusion: In different chemotherapy regimens in patients with lymphoma, remission, ever use MTX and/or Ara-c treatment and collecting the outer peripheral hematocrit could significantly affect the success rate of stem cell collection; In MM patients, who received lenalidomide treatment and multiple courses of treatment, still not got CR, which these reasons were the factors of non- successful mobilization.Although Plerixafor and peripheral blood CD34-positive cell counts could help to improve the success collection rate and predict collection rate, but there is still a need for further improvement of the current mobilization protocols, recognizing the ideal stem cell collection dynamics, efficiency and cost in order to select the appropriate mobilization protocols. Disclosures No relevant conflicts of interest to declare.

Mobilization, Harvesting and Selection of Peripheral Blood Stem Cells in Patients with Autoimmune Diseases Undergoing Non-Myeloablative Autologous Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1980-1980
Author(s):  
Laisvyde Statkute ◽  
Larissa Verda ◽  
Yu Oyama ◽  
Marcelo Villa ◽  
Thomas Shook ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Autoimmune Diseases ◽  
Peripheral Blood ◽  
Hematopoietic Stem ◽  
Positive Correlation ◽  
Cd34 Cells ◽  
The Mean ◽  
Stem Cell Collection ◽  
Selection Of

Abstract We have analyzed peripheral blood stem cell (PBSC) mobilization, harvesting and selection properties in 128 patients with severe autoimmune diseases undergoing non-myeloablative autologous hematopoietic stem cell transplantation (HSCT) (50 patients with systemic lupus erythematosus (SLE), 43 - with multiple sclerosis (MS), 15 - with Crohn’s disease (CD), 8 - with scleroderma (Scl), and 12 - with others). Female/male ratio and mean age (range) were 90/38 patients, and 34 (14 to 59) years old, respectively. Mobilization regimen included cyclophosphamide 2g/m2 and G-CSF 10 mcg/kg (except for SLE patients 5 mcg/kg). Forty one patients underwent stem cell collection using Baxter CS300, 78 patients - Spectra, and for 9 patients both apheresis machines were utilized. The mean number of aphereses was 1.8 (range 1–10). Patients with SLE required the largest number of apheresis sessions (mean 2.4), comparing to patients with CD (mean 1.9), Scl (mean 1.4), MS (mean 1.3). Five patients additionally required bone marrow harvest for collection of adequate numbers of stem cells. One patient failed to reach CD34+ cell number of 1.0x106/kg, therefore did not proceed to HSCT. The mean number of CD34+ cells in each apheresis unit was 6.07+−6.96x106/kg (the highest of 9.22+−8.52x106/kg in patients with MS, and the lowest of 3.93+−4.48x106/kg in patients with SLE). Ninety eight patients underwent stem cell selection with CEPRATE SC (N=18), Isolex 300iv1.12 (N=2) or Isolex 300iv2.5 (N=78) stem cell concentrator. The mean purity of selected products was 74.3% (the highest of 81.1% attained in patients with Scl); mean recovery of CD34+cells was 61.2%. T cell reduction by average of 3.7 logs was achieved. The mean number of infused CD34+ cells was 7.24+−5.5x106/kg. The highest mean number of CD34+ cells/kg were infused to patients with MS (9.04+−6.74x106/kg), the lowest - to patients with SLE (5.78+−4.13x106/kg). We found a moderate positive correlation between peripheral blood (PB) CD34+ cells/ul and PB WBC/ul (R=0.34, p<0.05), PB platelets/ul (R=0.51, p<0.05) and a strong positive correlation between PB CD34+ cells/ul and the number of CD34+ cells/kg/apheresis (R=0.67, p<0.05). A weak positive correlation was observed between the number of infused CD34+cells/kg and faster WBC engraftment (ANC>500) and platelet engraftment (platelet count>20K). There was no toxicity observed in our patient population during peri-mobilization period except for 1 patient with SLE who died of disseminated mucormycosis 1 week after stem cell collection. Mobilization and selection of PBSC are safe and efficient in patients with severe autoimmune diseases undergoing non-myeloablative autologous HSCT.

A Mobilizing Regimen of AMD3100 and G-CSF Increases Stem Cell Collection in Patients with Hodgkin’s Disease, and PK Is Similar to That of Non-Cancer Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3053-3053 ◽  
Author(s):  
Amanda F. Cashen ◽  
Gary Calandra ◽  
Ron MacFarland ◽  
Sandra Lopez ◽  
John F. DiPersio
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Plasma Concentrations ◽  
Control Group ◽  
Peripheral Blood Stem Cells ◽  
Platelet Recovery ◽  
Cd34 Cells ◽  
Historical Controls

Abstract For patients undergoing autologous peripheral blood stem cell transplantation (PBSCT), the number of CD34+ cells collected is a reliable predictor of neutrophil and platelet engraftment after transplantation, with doses > 5 x 106 CD34+ cells/kg associated with faster count recovery. Unfortunately, collection of an adequate number of peripheral blood stem cells (PBSCs) can be difficult in Hodgkin’s disease (HD) patients. AMD3100 reversibly inhibits the binding of stromal cell-derived factor 1 (SDF-1), constitutively expressed on bone marrow stromal cells, to its receptor CXCR4, expressed on CD34+ cells. AMD3100 combined with G-CSF has been shown to improve PBSC collection compared to mobilization with G-CSF alone in patients with multiple myeloma or non-Hodgkin’s lymphoma (Blood2005;106:1867). This study was undertaken to determine whether a mobilization regimen of AMD3100 + G-CSF can safely and effectively mobilize PBSCs in patients with HD who are undergoing autologous PBSCT. Results were compared to a historical control group comprised of 98 consecutive HD patients who underwent G-CSF-alone mobilization at our institution. Patients were followed post-transplant to evaluate engraftment timing and durability. Pharmacokinetic (PK) determinations were completed in a subset of patients (n=6) following the first dose of AMD3100. To date, 19 patients with relapsed (17) or refractory (2) HD have been mobilized with G-CSF (10 ug/kg/d) + AMD3100 (240 ug/kg/d sc at 10 p.m. beginning on day 4). Apheresis was performed 11 hours after each AMD3100 dose. The first dose of AMD3100 produced a median (range) 3.0 (1.9–12) fold increase in the number of circulating CD34+ cells. Twelve patients (63%) achieved a collection of ≥ 5 x 106 CD34+ cells/kg, a significantly higher proportion than historical controls (15%, p=0.049). Eighteen patients (95%) mobilized with AMD3100 + G-CSF collected > 2 x 106 CD34+ cells/kg (range, 0.9–9.6 x 106 CD34+ cells/kg), compared to 78% of controls (p=0.116). The median (range) number of apheresis procedures performed per patient was 2 (1–5). The median collection in the first two days of pheresis was 5.0 x 106 CD34+ cells/kg, which is significantly better than historical controls, who collected a median 3.0 x 106 CD34+ cells/kg in the first two days of pheresis (p=0.002). No grade II-IV adverse events were ascribed to AMD3100. Eighteen patients were transplanted with G-CSF + AMD3100 mobilized cells. All had prompt and stable engraftment, with median neutrophil recovery at day +9 (8–11) and median platelet recovery at day +15 (9–20). PK studies demonstrated that AMD3100 was rapidly absorbed following subcutanetous injection, with a median (range) Cmax of 0.87 (0.66–1.16) ug/ml. Plasma concentrations declined in a bi-exponential manner, with a median elimination half-life of 3.7 (2.4–4.0) hours. The median AUC0–infinity was 3,749 (2,808–4,761) ug-hr/ml. AMD3100 pharmacokinetics in this patient population are consistent with results previously obtained from healthy volunteers in the absence of G-CSF. We conclude that AMD3100 + G-CSF is a well-tolerated and effective mobilization regimen in patients with HD. For these patients, AMD3100 + G-CSF can improve the number of PBSCs collected and decrease the number of days of pheresis.

Abstract 239: Stem Cell Therapy Improves Critical Limb Ischemia

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Alaa Marzouk
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Embryonic Stem ◽  
Limb Ischemia ◽  
Control Group ◽  
Chronic Limb Ischemia

Introduction: The journey from single cell to complex being is attributable to stem cells role. Adult stem cells originate during ontogeny & persist in specialized niches within organs. Asymmetric division of each stem cell during differentiation produces : one daughter stem cell & one daughter transit amplifying/intermediate cell having migratory properties. Forced migration of hematopoietic stem/progenitor cells (HSPC) from bone marrow into peripheral blood is called mobilization. Accumulating evidence suggests that attenuation of the chemokine stromal derived factor-1(SDF-1)-CXCR4 axis that plays a pivotal role in retention of HSPC in bone marrow (BM) results in the release of these cells from the BM into peripheral blood. Recently, adult cells have been genetically reprogrammed to an embryonic stem cell like state. Induced pluripotent stem cells (IPSCs) were similar to human embryonic stem cells in morphology, proliferative capacity, expression of cell surface antigens, & gene expression. Treatment of ischemic vascular disease of lower limbs remains a significant challenge. Unfortunately, if medical & surgical salvage procedures fail, amputation is an unavoidable result for those patients. Aim of Work: (Hypothesis) To assess the application of implantation of autologous stem/progenitor cell in the treatment of chronic limb ischemia & to evaluate the safety, efficacy & feasibility of this novel therapeutic approach. Methods: A total of 24 patients with chronic limb ischemia not eligible for arterial reconstruction or endovascular procedures were enrolled & randomized (1:1) to either the implanted group or the control group. Control group: Conventional medical therapy in the form of anti platelet therapy & vasodilators. Implanted group: Subcutaneous injection of 300μ g/day of recombinant human granulocyte colony stimulating factor (G-CSF) for 5 days to mobilize stem/progenitor cells from BM. Total leucocytic count is measured daily to follow up successful mobilization of bone marrow mononuclear cells (BMMNCs). Stem cell Harvesting After 5 days peripheral blood mononuclear cells (PBMNCs) were harvested using a cell separator. Samples from apheresis products are subjected to TLC measurement & immunophenotypic characterization of CD34+ cells by flow cytometry. The collected PBMNCs were implanted by multiple intramuscular injections into ischemic limbs. Results: There was significant increase in pain free walking distance & ankle/brachial index (ABI) & significant decreased rest pain. Effectiveness was documented by : reduced number of amputation, increase ABI & improvement of the quality of life in therapeutic group compared to control group. Conclusion: The novel therapeutic approach of PBMNCs implantation in patients with chronic limb ischemia is safe, feasible & effective in decreasing co-morbidity & rate of amputation. Safety was manifested by absence of complications during G-CSF therapy or during harvesting & injection of the stem cells. Recommendations: 1- Future studies on larger number of patients & longer follow up. 2- Controlled studies using different methods & different cell population (PBMNCs, BMMNCs or MSCs) to compare the outcome of each. 3-Studing the role of endothelial progenitor cell dysfunction in different ischemic diseases to develop successful gene therapy.

scholarly journals Impact of Induction Treatment on Stem Cell Collection: A COVID Related Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4848-4848
Author(s):  
Brad Rybinski ◽  
Ashraf Z. Badros ◽  
Aaron P. Rapoport ◽  
Mehmet Hakan Kocoglu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Research Funding ◽  
Median Number ◽  
Cell Transplant ◽  
Cd34 Cells ◽  
Significant Difference ◽  
Number Of Cycles ◽  
Time Required ◽  
Stem Cell Collection

Abstract Introduction: Standard induction therapy for multiple myeloma consists of 3-6 cycles of bortezomib, lenalidomide, and dexamethasone (VRd) or carfilzomib, lenalidomide and dexamethasone (KRd). Receiving greater than 6 cycles of a lenalidomide containing regimen is thought to negatively impact the ability to collect sufficient CD34+ stem cells for autologous stem cell transplant (Kumar, Dispenzieri et al. 2007, Bhutani, Zonder et al. 2013). Due to the COVID-19 pandemic, at least 20 patients at University of Maryland Greenebaum Comprehensive Cancer Center (UMGCC) had transplant postponed, potentially resulting in prolonged exposure to lenalidomide containing induction regimens. Here, in the context of modern stem cell mobilization methods, we describe a retrospective study that suggests prolonged induction does not inhibit adequate stem cell collection for transplant. Methods: By chart review, we identified 56 patients with multiple myeloma who received induction with VRd or KRd and underwent apheresis or stem cell transplant at UMGCC between 10/1/19 and 10/1/20. Patients were excluded if they received more than 2 cycles of a different induction regimen, had a past medical history of an inborn hematological disorder, or participated in a clinical trial of novel stem cell mobilization therapy. We defined 1 cycle of VRd or KRd as 1 cycle of "lenalidomide containing regimen". In accordance with routine clinical practice, we defined standard induction as having received 3-6 cycles of lenalidomide containing regimen and prolonged induction as having received 7 or more cycles. Results: 29 patients received standard induction (Standard induction cohort) and 27 received prolonged induction (Prolonged induction cohort) with lenalidomide containing regimens. The median number of cycles received by the Standard cohort was 6 (range 4-6), and the median number of cycles received by the Prolonged cohort was 8 (range 7-13). The frequency of KRd use was similar between patients who received standard induction and prolonged induction (27.58% vs. 25.93%, respectively). Standard induction and Prolonged induction cohorts were similar with respect to clinical characteristics (Fig 1), as well as the mobilization regimen used for stem cell collection (p = 0.6829). 55/56 patients collected sufficient stem cells for 1 transplant (≥ 4 x 10 6 CD34 cells/kg), and 40/56 patients collected sufficient cells for 2 transplants (≥ 8 x 10 6 CD34 cells/kg). There was no significant difference in the total CD34+ stem cells collected at completion of apheresis between standard and prolonged induction (10.41 and 10.45 x 10 6 CD34 cells/kg, respectively, p = 0.968, Fig 2). Furthermore, there was no significant correlation between the number of cycles of lenalidomide containing regimen a patient received and total CD34+ cells collected (R 2 = 0.0073, p = 0.5324). Although prolonged induction did not affect final stem yield, prolonged induction could increase the apheresis time required for adequate collection or result in more frequent need for plerixafor rescue. There was no significant difference in the total number of stem cells collected after day 1 of apheresis between patients who received standard or prolonged induction (8.72 vs. 7.96 x 10 6 cells/kg, respectively, p = 0.557). However, patients who received prolonged induction were more likely to require 2 days of apheresis (44% vs. 25%, p = 0.1625) and there was a trend toward significance in which patients who received prolonged induction underwent apheresis longer than patients who received standard induction (468 vs 382 minutes, respectively, p = 0.0928, Fig 3). In addition, longer apheresis time was associated with more cycles of lenalidomide containing regimen, which neared statistical significance (R 2 = 0.0624, p = 0.0658, Fig 4). There was no significant difference between standard and prolonged induction with respect to the frequency of plerixafor rescue. Conclusions: Prolonged induction with lenalidomide containing regimens does not impair adequate stem cell collection for autologous transplant. Prolonged induction may increase the apheresis time required to collect sufficient stem cells for transplant, but ultimately clinicians should be re-assured that extending induction when necessary is not likely to increase the risk of collection failure. Figure 1 Figure 1. Disclosures Badros: Janssen: Research Funding; J&J: Research Funding; BMS: Research Funding; GlaxoSmithKline: Research Funding.

scholarly journals Platelet Decrease and Efficacy of Platelet-Rich Plasma Return for Peripheral Blood Stem Cell Apheresis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Takahiro Shima ◽  
Teppei Sakoda ◽  
Tomoko Henzan ◽  
Yuya Kunisaki ◽  
Takahiro Maeda ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Platelet Count ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Platelet Rich Plasma ◽  
Blood Stem Cell ◽  
Platelet Recovery ◽  
Platelet Counts ◽  
Cd34 Cells

Peripheral blood stem cell (PBSC) transplantation is a key treatment option for hematological diseases and widely performed in clinical practice. Platelet loss is the major complication of PBSC apheresis, and platelet-rich plasma (PRP) return is recommended in case of severe platelet decrease following apheresis; however, little is known about the frequency and severity of platelet loss nor the efficacy of PRP return post-apheresis. To address these questions, we assessed changes in platelet counts following PBSC-related apheresis in 270 allogeneic (allo)- and 105 autologous (auto)-PBSC settings. We also evaluated efficacy of PRP transfusion on platelet recovery post-apheresis. Platelet counts reduced up to 70% post-apheresis in both allo- and auto-PBSC settings, while severe platelet count decrease (&lt; 50 x 109/L) was only observed in auto-PBSC patients (Figure 1). We next analyzed the relationship between severe platelet (&lt; 50 x 109/L) after apheresis and several clinical factors by using univariate and multivariate analysis for auto-PBSC patients. As shown in Table 1, in univariate analysis, severe platelet counts following auto-PBSC apheresis was found more frequently in patients with lower platelet count, lower percentage of CD34+ cells in PB at pre-apheresis, repeated round of apheresis, and smaller number of collected CD34+ cells. On the other hand, in multivariate analysis, the white blood cell (WBC) counts pre-apheresis was the only significant risk factor of severe platelet count following apheresis (p = 0.038). We finally analyzed the transitions of platelet counts in the setting of apheresis. The median platelet counts at pre-apheresis, post-apheresis, and post-PRP return were 187.0 x 109/L, 132.0 x 109/L, and 154.0 x 109/L for allo-PBSC apheresis, and 147.0 x 109/L, 111.0 x 109/L, and 127.0 x 109/L for auto-PBSC apheresis (p &lt; 0.0001 for all, allo-PBSC donors and auto-PBSC patients, respectively) (Figure 2), indicating that PRP return post-apheresis facilitated a rapid platelet recovery in both allo- and auto-settings. Collectively, our data suggest that WBC counts pre-apheresis is a useful predictor for severe platelet decrease following auto-PBSC apheresis and that PRP return is an effective mean to facilitate platelet recovery post-apheresis. Disclosures No relevant conflicts of interest to declare.

Transplantation of Peripheral Blood Stem Cells Mobilized by Chemotherapy and Single Dose Pegylated G-CSF in Patients with Multiple Myeloma: Equivalence of 6 mg and 12 mg Pegfilgrastim.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2868-2868 ◽  
Author(s):  
Ingmar Bruns ◽  
Ulrich Steidl ◽  
Christof Scheid ◽  
Kai Hübel ◽  
Roland Fenk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Single Dose ◽  
Peripheral Blood ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cytotoxic Therapy ◽  
Cd 34 ◽  
Cd34 Cells

Abstract To date the most effective treatment for patients (pts) with multiple myeloma consists of conventional induction chemotherapy followed by either single or tandem high-dose chemotherapy and autologous blood stem cell transplantation. Collection of sufficient numbers of hematopoietic stem cells is essential for high-dose chemotherapy. Current regimens for stem cell mobilization are based on daily subcutaneous injections of human recombinant G-CSF starting shortly after cytotoxic therapy. Here we examined the use of polyethyenglycole (PEG)-conjugated G-CSF (pegfilgrastim) at two different doses in patients with stage II or III multiple myeloma. Patients received induction therapy with 2–4 cycles ID or VAD. Following cytotoxic therapy with cyclophosphamide (4g/m2) we administered either a single dose of 6 mg pegfilgrastim (n=10 pts; median age: 55 years), 12 mg pegfilgrastim (n=12 pts; median age: 51 years) or daily doses of 8,5 μg/kg unconjugated G-CSF (filgrastim) (n=12 pts; median age: 51 years). The growth factor was given on day 4 (range 2–5 days) in the “6 mg pegfilgrastim group”, on day 5 (range 2–7 days) in the “12 mg pegfilgrastim group” and on day 4 (range 3–6 days) in the “filgrastim group” after cyclophosphamide. Numbers of CD34+ cells were determined during leukocyte recovery and harvested by large volume apheresis using a cobe spectra blood cell separator. Pegfilgratim was associated with an earlier leukocyte recovery both at the 6mg dose (median 12 days, range 8–16 days) and the 12mg dose (median 12 days, range 7–16 days) as compared to filgrastim (median 14 days, range 11–15 days, p=0.04). Similarily, the peripheral blood CD34+ cell peak occurred earlier in patients who received pegfilgrastim (median 12 days, range 11–18 days versus median 15 days, range 12–18). On the other hand the peripheral blood CD 34+ peak did not differ significantly between the three groups (median 129/μl with 6 mg pegfilgrastim, range 30–433, median 78/μl with 12 mg pegfilgrastim, range 20– 1055 and median 111/μl with filgrastim, range 28–760, p=0.95). With a median of 1.0x10E7 CD34+ cells per kg (range 5.8x10E6-1.9x10E7) in the “6 mg pegfilgrastim group”, 7.4x10E6 CD34+ cells per kg (median, range 4.9x10E6- 3.8x10E7) in the “12 mg pegfilgrastim group” and 10.8x10E6 CD34+ cells per kg (median, range 5.0x10E6-8.7x10E7) in the “filgrastim group” there were no significant differences in the total number of harvested CD34+ cells. Following high-dose therapy with melphalan (200 mg/m2) and autografting leukocyte and platelet reconstitution was similar within all groups. In summary, a single dose of pegfilgrastim after high dose cyclophosphamide is capable of mobilizing a sufficient number of CD 34+ cells for succesful autografting and sustained hematological reconstitution in patients with multiple myeloma. No difference could be observed between 6 mg and 12 mg of pegfilgrastim. Our data provide the basis for randomized studies evaluating the optimal dose and timing of pegfilgrastim as well as long-term outcome in larger cohorts of patients.

Purified T Depleted Peripheral Blood and Bone Marrow Cd34 Transplantation from Haploidentical Mother to Child with Thalassemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3106-3106
Author(s):  
Pietro Sodani ◽  
Buket Erer ◽  
Javid Gaziev ◽  
Paola Polchi ◽  
Andrea Roveda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
T Cell ◽  
Peripheral Blood ◽  
Therapeutic Option ◽  
B Cell Lymphoma ◽  
Marrow Transplant ◽  
Hematopoietic Stem ◽  
Cd34 Cells

Abstract Approximately 60% of thalassemic patients can not apply to “gene therapy today” which the insertion of one allogenic HLA identical stem cell into the empty bone marrow as the vector of the normal gene for beta globin chain synthesis. We studied the use of the haploidentical mother as the donor of hematopoietic stem cells assuming that the immuno-tollerance established during the pregnancy will help to bypass the HLA disparity and allow the hemopoietic allogeneic reconstitution in the thalassemic recipient of the transplant. We have employed a new preparative regimen for the transplant in fourteen thalassemic children aged 3 to 12 years (median age 5 years) using T cell depleted peripheral blood stem cell (PBSCTs) plus bone marrow (BM) stem cells. All patients received hydroxyurea (OHU) 60 mg/kg and azathioprine 3 mg/kg from day -59 until day-11, fludarabine (FLU) 30 mg/m 2 from day -17 to day -11, busulphan (BU) 14 mg/kg starting on day -10, and cyclophosphamide(CY) 200mg/kg, Thiotepa 10 mg/kg and ATG Sangstat 2.5 mg/kg, followed by a CD34 + t cell depleted (CliniMacs system), granulocyte colony stimulating factor (G-csf) mobilized PBSC from their HLA haploidentical mother. The purity of CD34+ cells after MACS sorting was 98–99%, the average number of transplanted CD34+ cells was 15, 4 x 10 6/kg and the average number of infused T lymphocytes from BM was 1,8 x 10 5/Kg.The patients received cyclosporin after transplant for graft versus host disease(GVHD) prophylaxis during the first two months after the bone marrow transplantation. Results. Thirteen patients are alive. Four patients rejected the transplant and are alive with thalassemia One patients died six months after bone marrow transplant for central nervous system diffuse large B cell lymphoma EBV related. Nine patients are alive disease free with a median follow up of 30 months (range12–47). None of the seven patients showed AGVHD and CGVHD. This preliminary study suggest that the transplantation of megadose of haploidentical CD34+ cell from the mother is a realistic therapeutic option for those thalassemic patients without genotipically or phenotipically HLA identical donor.

Peripheral Blood Stem Cell Harvests Performed Beyond the Initial Two Days of Apheresis May Not Contribute to Accelerate Granulocyte and Platelet Engraftment After Autologous Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3226-3226
Author(s):  
Luciano Wannesson ◽  
Lisa Wang ◽  
John Kuruvilla ◽  
Tracy Nagy ◽  
Ronnie Saragosa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Peripheral Blood ◽  
High Dose ◽  
Platelet Recovery ◽  
Neutrophil Recovery ◽  
Cell Dose ◽  
Group I ◽  
Cd34 Cells

Abstract Abstract 3226 Poster Board III-163 Introduction Measurement of the number of CD34+ cells in the leukapheresis product is universally used as a surrogate measure of the capacity of peripheral blood stem cells (PBSC) to reconstitute hematopoiesis. Early studies demonstrated that engraftment times are shorter and predictable if at least 5 ×106 CD34+ cells/kg are administered following high-dose chemotherapy. However, satisfactory neutrophil and platelet recovery occurs after infusions of >2.0 ×106 CD34+ cells/kg. Previous analyses demonstrated the presence of different subsets of CD34+ cells in the peripheral blood at different times during mobilization, with pluripotent subsets arising and decreasing earlier after mobilization and more committed subsets peaking later [Stewart et al, Exp Hematol 1995; 23: 1619-27]. We hypothesized that for equivalent CD34+ cell dose, there could be a difference in engraftment kinetics according to the number of days of apheresis required to obtain an adequate PBSC graft. Patients and Methods Data from 270 consecutive autografts performed between July 1999 and April 2006 for non-Hodgkin and Hodgkin lymphoma (58% and 25%, respectively), breast cancer (8%), germ-cell tumors (2%) and acute myeloid leukemia (7%) were analyzed. Mobilization was performed using cyclophosphamide +/- etoposide + G-CSF 10μg/kg; patients received G-CSF after PBSC infusion from day 10 until neutrophil recovery >1500/μL. Patients were stratified in 3 groups according to the SC dose administered as follows: Low-dose (L) <2 ×106 CD34+ cells/kg, Intermediate-dose (I) 2 to 5 ×106 CD34+ cells/kg and High-dose (H) >5 ×106 CD34+ cells/kg and in 2 categories according to the number of days of apheresis performed (≤2 and 3+). The data analysis was divided in 3 steps. Step 1: we made a comparison of engraftment results for group L vs. I and I vs. H. Step 2: to explore potential engraftment differences within each cell dose stratum according to the number of days of apheresis required, that is, I(≤2) vs. I(3+) and H(≤2) vs. H(3+). Step 3: to test the influence of performing additional harvests beyond day 2 on engraftment kinetics we compared group I(≤2) vs. group H(3+), i.e. those who obtained the optimal number of CD34+ cells through additional collections during the same mobilization. Differences between groups were estimated by the Mann-Whitney test and by Cox regression model. Results The step 1 analysis confirmed that engraftment was faster for the H group (N=138, median 11 days for ANC>500/μl and N=132, median 11 days for unsupported platelet count >20000/μl) than for the I group (N=118, median 11 days and N=98, 12 days for neutrophils and platelets, respectively) and the L group (N=14, median 12 days and N=12, median 15 days for neutrophils and platelets, respectively). Two-sided p-values favored I in L vs. I (p=0.0185 for neutrophils and p=0.0013 for platelets) and favored H in I vs. H (p=0.0002 for neutrophils and p=0.019 for platelets). The step 2 analysis did not show any statistical difference in engraftment times within groups L, I and H, according to the number of apheresis (≤2 vs. 3+), but there was a trend for faster platelet engraftment for patients in the ≤2 group (p=0.08). There was no difference between the ≤2 and 3+ subgroups in terms of age and number of chemotherapy lines received before transplant; although, in the ≤2 group there were more patients with breast cancer (10.3% vs. 4.8%) and Hodgkin lymphoma (32.2% vs. 16.1%) and fewer pts with non-Hodgkin lymphoma (66.1% vs. 48%) compared to the 3+ group (p<0.001). Step 3 analysis showed no difference for neutrophil recovery between subgroups I≤2 and H3+ (N=28, median 11 days for I≤2 and N=20, median 10 days for H3+, p=0.08) and platelet engraftment (median 11 days for I≤2 and 12 days for H3+, p=0.54). Even dough, patients in the I≤2 cohort received significantly less CD34+ cells/kg (median 4.46, range 2.10-4.99) compared to those in the H3+ group (median 6.33, range 5.10-8.99, p<0.001) and were similar in terms of age and number of lines of prior therapy. Conclusions Provided more than 2 ×106 CD34+ cells/kg are obtained in two days of leukapheresis, optimal engraftment times can be achieved even if the threshold of 5 ×106 CD34+ cells/kg is not reached. Our results suggest that the addition of harvest days beyond 2 days to obtain ≥5 ×106 CD34+ cells/kg may not contribute to improved short-term engraftment kinetics. Disclosures No relevant conflicts of interest to declare.

Ex-Vivo Expanded Peripheral Blood Stem Cells (EVEC) Compared with Un Manipulated Peripheral Blood Stem Cells (PBSC) Autologous Transplantation for Multiple Myeloma: A Pair Match Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 502-502 ◽  
Author(s):  
Noel-Jean Milpied ◽  
Gerald Marit ◽  
Bernard Dazey ◽  
Jean-Michel Boiron ◽  
Zoran Ivanovic ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Abstract 502 Autologous stem cell transplantation with PBSC after high-dose chemotherapy remains standard therapy for patients with symptomatic Multiple Myeloma (MM). Strategies to minimize complications could significantly reduce the morbidity of that procedure. One possibility could be to shorten the duration of induced neutropenia through the injection of an ex-vivo expanded graft. Nineteen patients (pts) received EVEC after high-dose Melphalan (HDM) (200 mg/m2) as the only graft. The ex-vivo expanded procedure has been described elsewhere (Boiron et al. Transfusion 2006 and Ivanovic et al. Transfusion 2006). Briefly, thawed peripheral blood CD 34+ cells collected after G-CSF mobilisation and selected with immunomagnetic devices were incubated for 10 days in a serum free medium (Maco Biotech HP01) with Stem Cell Factor (Amgen), G-CSF (Amgen) and TPO (Amgen: 7 pts; Cellgenix:12 pts). The expanded cells were then thoroughly washed and injected 48h after the HDM injection. The ex-vivo expansion lead to a median fold of 5,4 for CD34+ cells (1,3-11,8); 118 for CD33+ (1-703880); 3386 for CD14+ (4-101075); 28,5 for CD13+ (10-703880) and 13 for CFUs (6-21). The median N° of CD34+ cells injected was 14×10e6/kg (5,3-48). The results of these transplants were compared to those achieved in 38 pts who received unmanipulated PBSC after HDM. Pts and controls were matched for age, sex, stage of the disease, first line chemotherapy ( VAD or VD) status of the disease at time of transplant, year of transplant, time between diagnosis and transplant, CD34+ mobilisation technique (HD cytoxan + G-CSF or G-CSF alone) and the median N° of total nucleated cells and of CD34+ collected. The results are summarized on the table: There was no secondary neutropenia in the patients who received EVEC. With a median FU of the entire cohort of 30 m, the median OS for pts who received their first transplant with EVEC and with PBSC is 69 m and not reached respectively (p=NS), the median PFS is 18 m and 27 m (p = NS) and the median time to progression is 14 m and 15 m (p=NS). Conclusion: EVEC is feasible, safe and reduce significantly the morbidity of autologous stem cell transplantation after HDM for multiple myeloma. Disclosures: Milpied: Amgen France: Honoraria.

Sign in / Sign up

Export Citation Format

Share Document