Mobilization of Blood Stem Cells with Recombinant Human (rh)G-CSF in Patients with Hematological Malignancies and Solid Tumors

1993 ◽  
pp. 155-167 ◽  
Author(s):  
R. Haas ◽  
S. Hohaus ◽  
R. Ehrhardt ◽  
H. Goldschmidt ◽  
B. Witt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Solid Tumors ◽  
Hematological Malignancies ◽  
Blood Stem Cells

Platelet-Derived Microparticles Accelerate Engraftment of Peripheral Blood Stem Cells in Human Allogeneic Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3035-3035
Author(s):  
Christiane de Rop ◽  
Jan Priesack ◽  
Andreas Tiede ◽  
Arne Trummer
Keyword(s):  
Stem Cells ◽  
Cell Count ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Positive Control ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells ◽  
The Impact

Abstract While the procoagulant activity of platelet derived microparticles (PMP) has been widely accepted, knowledge regarding their immunological and adhesive qualities is still limited. It has been shown that murine BM cells covered with PMP engrafted lethally irradiated mice significantly faster than those not covered, indicating that PMPs play an important role in the homing of peripheral blood stem cells (PBSC). Here we studied the impact of PMP on engraftment in human allogeneic PBSC transplants for patients with hematological malignancies. PBSC samples were collected in buffered citrate from transplantation bags after infusion of transplants into patients with hematological malignancies (AML = 5, ALL = 1). Conditioning regimens included busulfan/cyclophosphamide (Bu/Cy), anti-CD66b-radioimmunotherapy (RIT)/Bu/Cy, and reduced intensity regimens with fludarabin/busulfan (Flu/Bu) and FLAMSA. Platelet-poor plasma (PPP) was prepared (1500g for 20min), immediately shock-frozen in liquid nitrogen and stored at −80°C. For further analysis PPP’s were carefully thawed at room temperature (RT). 90μl of PPP was stained with 5μl of CD41-PE and CD62P-FITC each for 15min at RT in the dark (IgG1-FITC and -PE served as negative controls, TRAP-6 (10μM) stimulated whole blood processed in same way as samples as positive control). To stop staining 900μl PBS/BSA 2% was added and 500μl of this solution were transferred into BD Trucount tubes by reverse pipetting giving a final concentration of 100 beads/μl. Samples were analyzed immediately using Coulter FC500 flow cytometer with CXP software. As expected the CD34 cell count (mean=5.1x106/kg body weight, SD=2.0x106/kg) showed a significant correlation (p=0.0197, Pearson r=−0.83) with the time to engraftment (mean=15.7days, SD=2.0d). The amount of CD62P positive microparticles (mean=423/μl, SD=119/μl) and the conditioning regimen showed no significant correlation with CD34 cell count or time to engraftment with leucocytes >1000/μl. In contrast, CD41-PMP count (mean=1223/μl, SD=857μl) correlated significantly with the CD34 cell count (p=0.0086, Pearson r=0.92) and the time to engraftment (p=0.0039, Pearson r = −0.95). Therefore, PBSCT contain significant amounts of PMP which are most likely generated during apheresis. Preliminary results show a stronger correlation with time to engraftment than does CD34 cell count. We conclude that PMP may accelerate engraftment of PBSC in humans. However, this function seems unrelated to P-Selectin expression. Therefore, further studies aiming to identify other adhesion molecules involved in PMP-mediated engraftment of PBSCT are warranted.

1136 Limited mobilization effect of G-CSF (lenograstim) for blood stem cells in children with solid tumors

1995 ◽  
Vol 31 ◽  
pp. S238
Author(s):  
Y. Kawano ◽  
Y. Takaue ◽  
Y. Kuroda ◽  
M. Ohira
Keyword(s):  
Stem Cells ◽  
Solid Tumors ◽  
Blood Stem Cells

Single-Dose Pegfilgrastim after Chemotherapy Is Highly Effective in Enhancing the Mobilization of Autologous CD34+ Peripheral Blood Stem Cells in Patients with Lymphoid Malignancies and Solid Tumors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2922-2922
Author(s):  
Frank Kroschinsky ◽  
Kristina Hoelig ◽  
Uwe Platzbecker ◽  
Eberhard Schleyer ◽  
Rainer Ordemann ◽  
...  
Keyword(s):  
Stem Cells ◽  
Single Dose ◽  
Solid Tumors ◽  
Peripheral Blood ◽  
Half Life ◽  
Peripheral Blood Stem Cells ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract The administration of myelosuppressive chemotherapy followed by daily injections of granulocyte-colony stimulating factor (G-CSF) is the common procedure to mobilize autologous CD34+ peripheral blood stem cells (PBPC). Pegfilgrastim (NeulastaTM, Amgen Inc., Thousand Oaks, USA) is a covalent conjugate of filgrastim and polyethylene glycol with an increased elimination half-life due to decreased serum clearance. Whereas a single injection of pegfilgrastim (PEGFIL) has been shown to be equivalent to daily filgrastim in enhancing neutrophil recovery after chemotherapy, the experiences with PEGFIL in mobilization of PBPC are limited. We report 40 pts (22 male, 18 female, median age 53 years) who had a PBPC mobilization treatment for Hodgkin′s lymphoma (n=3), non-Hodgkin′s lymphoma (n=13), multiple myeloma (n=16), acute lymphoblastic leukaemia (n=3) or solid tumors (n=5). The mobilization regimen consisted of disease specific chemotherapy and a single subcutaneous injection of 6 mg PEGFIL administered 48 hours after the end of cytotoxic treatment (day 0). CD34+ cells in the peripheral blood (PB-CD34) were measured if white blood cells (WBC) exceeded 1.0 Gpt/L after nadir. PBPC collections started at a PB-CD34 cell count >10/μl and were performed as large-volume apheresis (4x blood volume) using a Cobe Spectra (Gambro BCT Inc.). Additional conventional filgrastim (FIL) was given at a dose of 2x5μg/kg if PB-CD34 count was found to be <10/μl. Blood samples for pharmacokinetics were taken in 9 pts. The median start of aphereses was on day +9 after the administration of PEGFIL and on day +15 after start of chemotherapy regimen, respectively. Median PB-CD34 peak was 74/μl (range 9–565/μl). The median PBPC yield was 7.6 x 10^6 CD34+ cells/kg (range 1.5–88.1). The target cell dose to be collected (≥ 2.5 x 10^6 CD34+ cells/kg) was achieved in 36 (90 %) pts, in 29 pts (72.5 %) ≥ 4.0 x 10^6 CD34+ cells/kg could be obtained with a single collection. Additional FIL administrations were necessary in 7 patients (17.5 %) for 2 to 6 days. All of them were heavily pretreated including a previous autologous transplant in two of these patients. PEGFIL was well tolerated except for moderate bone pain which occurred in all patients. The mean values (± SD) for peak plasma concentration of PEGFIL (cmax), time to reach the maximum plasma level (tmax) and elimination half-life (t1/2) were 154 (± 83) ng/ml, 56 (±21) hours and 23 (± 9) hours, respectively. We conclude that a single dose of 6 mg PEGFIL after chemotherapy is safe and highly effective in enhancing the mobilization of CD34+ PBPC for stem cell collection. Further investigations are warranted, including comparison with non-pegylated G-CSFs and in combination with antiadhesive agents.

scholarly journals To Predict Success of Postapheresis Yield and Post–Autologous Transplant Engraftment Based on Preapheresis Peripheral Blood CD34+ Cell Counts: An Indian Scenario–Based Study

2021 ◽  
Author(s):  
Pinki Devi ◽  
Ganapathi Bhat ◽  
Harish S. Ahuja
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Count ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Peripheral Blood Stem Cells ◽  
Peripheral Blood Cd34 ◽  
Cell Counts ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Introduction The use of hematopoietic stem cells for autologous and allogeneic transplantation has increased in the recent past significantly, due to introduction of newer chemotherapeutic drugs, immunological techniques, and better stem cell technology. Among the bone marrow and peripheral blood stem cells, collection of the latter being more convenient to the patient and associated with faster granulocyte and platelet engraftment has been known as preferred method for mobilization. Peripheral blood stem cells can be extracted from the autologous or allogeneic donor. Mobilization of the stem cells for autologous stem cell transplant is traditionally done using growth factors alone or in combination with chemotherapy, with or without an additional mobilizing agent. A significant number of hematological malignancy patients are poor mobilizers, (i.e., they are unable to achieve the minimal target cell dose during their first round of mobilization).Therefore, a prediction for a successful stem cell mobilization ideally should be made before initiating any apheresis procedure to spare those with a low rate of success from the risks associated with apheresis procedure. Preapheresis CD34 cell count can predict postapheresis yield and hence, can help to reduce the collection sessions. Reduction of apheresis sessions decreases the discomfort, inconvenience, time, and monetary expenses. Objectives This study was aimed to analyze preapheresis and postapheresis CD34+ cell counts. Materials and Methods Patients of any age and gender with diagnosis of hematological malignancies admitted for autologous stem cell transplantation for hematological malignancies (including Hodgkin lymphoma, non-Hodgkin lymphoma, and multiple myeloma) and germ cell tumors in our institute from July 2008 to July 2016 were included in the study. The post-GCSF CBC, preapheresis CBC, CD34+ cell counts, and postapheresis CBC, CD34+ cell counts, mononuclear cell counts to predict the outcome of amount of yield. The effect on engraftment will be measured according to the defining criteria of achieving a sustained peripheral blood neutrophil count of >500 × 106/L (Wolff 2002) and a platelet count of more than >20 × 109/L (Teltschik et al. 2016) independent of platelet transfusion for at least 7 days. Collection of stem cells was done using apheresis machine (COBE SPECTRA). Complete peripheral blood counts using automated analyzers. Peripheral blood CD34 + cell counts and postapheresis CD34+ cell count using BD FACS CANTO II flow cytometer. To calculate postapheresis yield, the related CD34 count measured by flow cytometer was multiplied by the apheresis product volume and divided by the recipient’s body weight (kg). Number of CD34+ cells collected = (CD34 cell concentration in final product) × (final product volume). Results A total of 100 patients who underwent a total of 320 apheresis sessions were included in the study. There were 78 males and 22 females. We also found a significant correlation between preapheresis CD34 + cell count and postapheresis CD34 percentage on days 1, 2, and 3 of the apheresis sessions. In our study, to obtain more than 1.31 × 106 cells (median = 1.04, range: 0.15–4.70), an absolute count of pre apheresis CD34 + cells ≥14 cells would be necessary. A target of CD34 + cells ≥ 2 × 106/kg was obtained in majority of patients if a concentration of ≥25 CD34 + cells was present in postapheresis collection. Conclusion Compiling our results with the previous published data, we conclude that there is a strong correlation between preapheresis absolute CD34 + cell counts and postapheresis CD34 + cell count. Our study also suggests that the minimum absolute cell count of >10 cells/μL is required, to achieve a target of >2–5 × 106 cells for postapheresis yield.

Unmanipulated Haploidentical Blood and Marrow Transplantation in High Risk Hematologic Malignancies

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5527-5527
Author(s):  
Benakli Malek ◽  
Ahmed Nacer Redhouane ◽  
Bouarab Hanane ◽  
Baazizi Mounira ◽  
Zerkout Sara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
High Risk ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Hemorrhagic Cystitis ◽  
Hematologic Malignancies ◽  
Peripheral Blood Stem Cells ◽  
Haploidentical Transplantation ◽  
Blood Stem Cells

Abstract Introduction: allogeneic haploidentical identical stem cells transplantation (SCT) is currently a salvage procedure in patients with hematologic malignancies at high risk and who have no HLA identical donor. The new modalities of haploidentical transplantation without in vitro T depletion of the donor, seem to allow rapid immune reconstitution and reduce the incidence of graft versus host disease (GVHD). This retrospective study presents the short-term results of this procedure in a single-center series, using a unmanipulated graft involving both bone marrow and peripheral blood stem cells after exposure to G-CSF donor. Material and Methods: From May 2013 to March 2015, 15 allografts SCT HLA-haploidentical were used in 14 pts with hematological malignancies (3 AML, 9 ALL, one acute CML and one lymphoblastic NHL). The median age is 24 years with a sex ratio of 2,5. Median time diagnosis-transplant is 27 months (2-74). At the time of transplant, 8 pts were in second complete remission and 3 pts in blast phase. The donor used was one of the two ascendants (father: 5, mother: 2) or sibling (brother: 5, sister: 3), median donors age 38 years (17-65). The degree of compatibility (HLA A, B and DR) is 3/6 (8 cases), 4/6 (6 cases) and 5/6 (1 case). CMV status between donor/recipient was high risk in 14 cases. ABO incompatibility is major in 3 cases, minor in 4 cases. The conditioning regimen associated Busilvex 9.6 mg/kg; Aracytine 8 g/m2; Endoxan 3.6 g/m2. The prevention of GVHD involved the Cyclosporine-Methotrexate association, MMF and Thymoglobulin 10 mg/kg. All pts received an association of bone marrow transplant and peripheral blood stem cells (from the donor receiving first G-CSF at a dose of 5 μg/kg) with a total average rate of NC: 8,9.108/kg , CD34: 11.29 106/kg (1,43-18,25), MNC: 8,9.108/kg (4.80-17.97), CD3: 3,61 108/kg (0.04-14), CD4: 1.36 108/kg (0,02-7.53), CD8: 1.24 108 (0,36-7.53). A second haploidentical allogeneic transplantation (from another donor) with Fluadarabine-Melphalan conditioning, was required in a pt who presented early rejection. Results: aplasia was observed in all pts with average duration of 21 days (15-21). The output is seen aplasia average J17 (12-23). No cases of VOD was observed. One pt presented an early rejection and received a second haploidentical transplantation. Acute GVHD occurred in 9 pts (64.2%) including 8 (57%) of grade II-IV; a chronic GVHD in 2 pts (18%) of extensive form. Seven pts (46%) developed CMV reactivation occurred in average d44 (35-67). Three cases of hemorrhagic cystitis (one grade 4) are observed on average d47 (30-75). Three pts (21%) relapsed four months after transplantation (all in blast phases at the time of graft). After a median follow-up of 11 months (4-25), 8 pts (58%) are alive and 6 pts (42%) died (digestive aGVH: 1, severe infection: 2, hemorrhagic cystitis: 1, relapse: 2). The actuarial overall survival and event-free survival at 28 months are 42.4% and 37.5% respectively. Conclusion: The results of the allogeneic SCT using unmanipulated haploidentical from the marrow and peripheral blood, after a myeloablative conditioning, seem encouraging in pts with hematological malignancies at advanced stages. Disclosures No relevant conflicts of interest to declare.

scholarly journals Non-cryopreserved peripheral blood stem cells autotransplants for hematological malignancies can be performed entirely on an outpatient basis

1998 ◽  
Vol 58 (3) ◽  
pp. 161-164 ◽  
Author(s):  
Guillermo J. Ruiz-Argüelles ◽  
Alejandro Ruiz-Argüelles ◽  
Beatriz Pérez-Romano ◽  
Antonio Marín-López ◽  
José Luis Delgado-Lamas
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Outpatient Basis ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells
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