Blood Hematopoietic Stem Cell Mobilization Research Articles

Analysis of Factors Affecting Hematopoietic Stem Cell Mobilization Efficiency and Early Hematopoietic Reconstruction Indicators during Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation.

Purpose To analyze the factors affecting the mobilization efficiency of hematopoietic stem cells and hematopoietic reconstruction indicators during autologous peripheral hematopoietic stem cell transplantation. Methods The clinical data of 54 patients who underwent autologous peripheral blood hematopoietic stem cell mobilization and transplantation at Xuzhou Central Hospital from May 2016 to April 2023 were retrospectively analyzed. The gender, age, disease type, mobilization regimen, number of chemotherapy sessions, G-CSF (granulocyte colony-stimulating factor) dosage, and platelet number at the time of collection were also collected. Moreover, the relationship between these indicators with mobilization results and hematopoietic reconstruction was analyzed. Results Results showed that age, disease type, and number of collections were significantly related to the mobilization results (number of CD34+ hematopoietic stem cells). Furthermore, multivariate analysis showed that the number of collections was an independent factor affecting mobilization efficiency. Similarly, age, platelet value at the time of collection, CD34+ stem cell value during collection, white blood cell count, and number of chemotherapy times were significantly related to the time of megakaryocytic hematopoietic reconstruction. Multifactor analysis found that age and platelet count were independent factors affecting the reconstruction time of the megakaryocytic system. However, no factor was related to the time of granulocyte hematopoietic reconstruction. Conclusion Platelet count and age when collecting hematopoietic stem cells are closely related to megakaryocytic hematopoietic reconstruction and are key indicators of early hematopoietic reconstruction after autologous hematopoietic stem cell transplantation.

Efficacy and Safety of Plerixafor Combined with G-CSF for Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization in Lymphoma Patients

To investigate the efficacy and safety of plerixafor combined with granulocyte colony-stimulating factor (G-CSF) in mobilizing peripheral blood hematopoietic stem cells in patients with lymphoma. The clinical data of lymphoma patients who received autologous hematopoietic stem cell mobilization using plerixafor combined with G-CSF from January 2019 to December 2021 were retrospectively analyzed. The patients received 3 kinds of mobilization regimens: front-line steady-state mobilization, preemptive intervention, and recuse mobilization. The acquisition success rate, excellent rate of collection, and incidence of treatment-related adverse reaction were counted. The influence of sex, age, disease remission status, bone marrow involvement at diagnosis, chemotherapy lines, number of chemotherapy, platelet count and number of CD34+ cells on the day before acquisition in peripheral blood on the collection results were analyzed to identify the risk factors associated with poor stem cell collection. A total of 43 patients with lymphoma were enrolled, including 7 cases who received front-line steady-state mobilization, 19 cases who received preemptive intervention, and 17 cases who received recuse mobilization. The overall acquisition success rate was 58.1% (25/43) after use of plerixafor combined with G-CSF, and acquisition success rate of front-line steady-state mobilization, preemptive intervention, and recuse mobilization was 100%, 57.9%(11/19), and 41.2%(7/17), respectively. The excellent rate of collection was 18.6%(8/43). A total of 15 patients experienced mild to moderate treatment-related adverse reactions. The number of CD34+ cells < 5 cells/μl in peripheral blood on the day before collection was an independent risk factor affecting stem cell collection. Plerixafor combined with G-CSF is a safe and effective mobilization regimen for patients with lymphoma. The number of CD34+ cells in peripheral blood on the day before collection is an predictable index for the evaluation of stem cell collection.

Application of Mecapegfilgrastim for Peripheral Blood Hematopoietic Stem Cell Mobilization in Patients With Hematologic Neoplasms and Analysis of Predictors for Poor Mobilization

To evaluate the efficacy of applying mecapegfilgrastim for peripheral blood hematopoietic stem cell (PBSC) mobilization in patients with hematologic neoplasms, and to investigate the influencing factors of PBSC collection. Patients who underwent PBSC mobilization in the Department of Hematology, Mianyang Central Hospital between April 2016 and May 2022 were retrospectively analyzed. The CD34 + cell collection results of two groups, the mecapegfilgrastim group ( n=28), or the PEG group, and the recombinant human granulocyte colony-stimulating factor (rhG-CSF) group ( n=30), were compared, and the influencing factors of collection failure were analyzed. The success rates of CD34 + cells collection in the PEG group and the rhG-CSF group were 75.0% and 63.3%, respectively ( P>0.05). The median CD34 + cell counts were 3.37×10 6/kg and 2.68×10 6/kg, respectively, showing no significant difference. After combined mobilization with plerixafor, the median counts of CD34 + cells collected in the PEG group and rhG-CSF group were 4.23×10 6/kg and 3.26×10 6/kg, respectively, showing no significant difference ( P>0.05). There was no significant difference in hematopoietic system reconstruction and infections between the two groups ( P>0.05). Multivariate analysis found non-plasma cell disease (odds ratio [ OR]=19.697, 95% confidence interval [ CI] : 1.501-258.537, P=0.023), anemia before collection ( OR=18.571, 95% CI: 1.354-254.775, P=0.029) and white blood cell count before collection under 32×10 9 L -1 ( OR=85.903, 95% CI: 4.947-1491.807, P=0.002) to be independent risk factors for PBSC collection failure. The effect of PBSC mobilization with mecapegfilgrastim was comparable to that of rhG-CSF in patients with hematologic neoplasms. Furthermore, combined mobilization with plerixafor was feasible and effective. Patients with leukemia or lymphoma, anemia, and WBC<32×10 9 L -1 before stem cell collection have a high probability of PBSC collection failure.

PBSC Mobilization for Auto-HSCT in Myeloma: Growth Factors Vs Growth Factors + Chemotherapy

PBSC Mobilization for Auto-HSCT in Myeloma: Growth Factors Vs Growth Factors + Chemotherapy

Severe, Reversible Acute Lung Injury During Autologous Hematopoietic Stem Cell Mobilization After Filgrastim in a Child With Neuroblastoma: A Case Report

Peripheral blood hematopoietic stem cell mobilization is widely performed in a variety of clinical facilities and is believed to be a safe outpatient procedure. In this report, we describe a child with neuroblastoma who developed an extremely severe acute lung injury after granulocyte colony-stimulating factor was used for peripheral hematopoietic stem cell mobilization.A 3-year-old boy with a medical history of patent foramen ovale and secundum atrial septal defect was diagnosed with an MYCN-amplified neuroblastoma and treated with chemotherapy. During stem cell mobilization with filgrastim, the boy was in very good clinical condition, with a peripheral white blood cell (WBC) count of 57.17 K/μL, but he suddenly deteriorated, and nausea, seizures, and nystagmus were observed. The patient developed dyspnea with hemoptysis, and lung computed tomography showed bilateral asymmetrical pulmonary opacification demonstrating an anteroposterior density gradient. Because of rapidly progressing circulatory and respiratory failure, the child was hospitalized in the intensive care unit. Corticosteroid therapy, broad-spectrum antibiotic therapy, and cardiovascular support with mechanical ventilation were immediately instituted, and the child recovered without sequelae.The presented case emphasizes that life-threatening complications can occur during granulocyte colony-stimulating factor administration, and patient surveillance is warranted, especially if high leukocyte counts are observed or the patient exhibits cardiopulmonary signs.

Clinical Analysis of Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization Regimen in Patients with Malignant Hematological Diseases

To analyze the factors influencing the mobilization and collection of peripheral blood hematopoietic stem cells (HSC) in the patients with malignant hematological diseases. The peripheral blood stem cells in 50 patients with hematological malignancies had been mobilized in the Hematology Department Zhongda Hospital. The factors, such as age, sex, mobilization regimen, disease status, cell separator were analyzed, and the effect of above-mentioned factors on stem cell mobilization was evaluated. And the correlation between WBC, Hb, Plt counts and CD34+ cell collection was anzlyzed. There was significant effect at mobilization regimen on the success rate and collection counts of CD34+ cells, while sex, age, interval between diagnosis and mobilization, previous chemotherapy regimen and bone marrow involvement showed no significant effect on stem cell collection. There was positively correlation of the WBC count, hemoglobin level of peripheral blood before apheresis with the collection of CD34+ cells . The WBC and MNC counts in peripheral blood before apheresis closely related with the success rate of mobilization. Chemotherapy plus combined with G-CSF mobilization regimens is superior to mobilization regimen of cytokine alone for collection of HSC. The WBC and MNC count in peripheral blood before apheresis can predict the optimal time for the PBSC collection and increase the success rate of mobilization and collection.

371 - Filgrastim Biosimilars for Peripheral Blood Hematopoietic Stem Cell Mobilization in Healthy Donors: A Five-Year Experience From a University Hospital in Mexico

371 - Filgrastim Biosimilars for Peripheral Blood Hematopoietic Stem Cell Mobilization in Healthy Donors: A Five-Year Experience From a University Hospital in Mexico

Clinical analysis of autologous peripheral blood hematopoietic stem cell mobilization regimen in 61 lymphoma patients

Clinical analysis of autologous peripheral blood hematopoietic stem cell mobilization regimen in 61 lymphoma patients

Biosimilar Filgrastim in Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization and Post-Transplant Hematologic Recovery.

To date, two kinds of Granulocyte Colony-Stimulating Factors (G-CSF) have been approved for autologous peripheral blood hematopoietic stem cell (PBSCs) mobilization and posttransplant hematologic recovery after high-dose chemotherapy: filgrastim (originator and biosimilar) and lenograstim. Biosimilar filgrastim has been approved on the basis of comparable efficacy and safety in clinical studies where it has been used as chemotherapy-induced febrile neutropenia prophylaxis, but no specific pre-registration studies have been published in the transplant setting. Hence, there is still general skepticism about the role of biosimilar G-CSFs in this setting of patients. This review of biochemical, pre-clinical and clinical data suggests significant comparability of biosimilar filgrastim with both originator filgrastim and lenograstim in autologous PBSCs mobilization and post-autograft hematologic recovery.

Identifying Inherited and Acquired Genetic Factors Involved in Poor Stem Cell Mobilization and Donor-Derived Malignancy

Analysis of the clinical characteristics of hematopoietic stem cell transplant (HSCT) donors has proven beneficial for identifying cases of heritable hematopoietic disorders. This study examines poor peripheral blood hematopoietic stem cell mobilization after granulocyte colony–stimulating factor administration among 328 donors as a potential marker for suspected familial predisposition to myeloid malignancies. Here, we present data comparing the clinical characteristics of poor-mobilizing versus nonpoor-mobilizing donors and the results of panel-based sequencing of hematopoietic genes in poor-mobilizing donors. From this analysis, we identified a novel case of a donor-derived myelodysplastic syndrome in an HSCT recipient that is consistent with clonal evolution of TET2-mutated clonal hematopoiesis of indeterminate potential (CHIP) within the donor. This study demonstrates the potential risk of using hematopoietic stem cells from a donor with CHIP and raises the question of whether there should be increased screening measures to identify such donors.

High efficiency of peripheral blood hematopoietic stem cell mobilization in multiple myeloma: one case report and literature review

Objective To explore the influential factors of obtaining high proportion of CD34+ cells in patients with multiple myeloma (MM) peripheral blood hematopoietic stem cell (HSC) mobilization. Methods One patient with MM who was 64 years old and hospitalized in Department of Hematology, Hainan Branch of Chinese PLA General Hospital was enrolled into this study on January 2014. The patient achieved complete remission after four courses of bortezomib + doxorubicin hydrochloride liposome + dexamethasone induction regimens. Then peripheral blood HSC was mobilized with bortezomib + high dose cyclophosphamide + dexamethasone regimens in combination with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human thrombopoietin (rhTPO). Mobilization effect was reported with its relevant literature reviewed. Results The proportion of CD34+ cells in HSC graft was 6.80%. The number of mononuclear cells and CD34+ cells in harvest of single collection was 3.17×108/kg and 19.20×106/kg, respectively. Engraftment time of neutrophil and platelet was 10 days and 12 days after HSC transplantation, respectively. Conclusions Chemotherapy in combination with rhG-CSF and rhTPO is effective and safety for autologous HSC mobilization in MM patient. As this research is just a case report, it still needs many large sample and multi-center randomized controlled trials to confirm whether it can be widely used in MM patients. Key words: Multiple myeloma; Hematopoietic stem cell transplantation; Hematopoietic stem cell mobilization

Adverse Events during Peripheral Blood Hematopoietic Stem Cell Mobilization in Light Chain Amyloidosis Patients

Adverse Events during Peripheral Blood Hematopoietic Stem Cell Mobilization in Light Chain Amyloidosis Patients

Fluid Retention and Weight Gain During Peripheral Blood Hematopoietic Stem Cell Mobilization in Light Chain Amyloidosis

Fluid Retention and Weight Gain During Peripheral Blood Hematopoietic Stem Cell Mobilization in Light Chain Amyloidosis

Abstract 4645: Preclinical development of RFF-1, a novel rational designed CXCL12 mimetic drug

Abstract The interaction between the chemokine receptor CXCR4 and its ligand, CXCL12, has been shown in pre-clinical models to facilitate tumour metastasis and to be involved in tissue repair and in recruitment of hematopoietic precursors. AMD3100, a potent CXCR4 antagonist, has been approved by FDA for stem cell mobilization in patients with multiple myeloma and non-Hodgkin lymphoma. Several other CXCR4 inhibitors are in clinical development (BTK140, CTCE-9908, MDX-1338 and POL6326), with the aim of inhibiting the development and progression of metastasis. In the rational design of CXCR4 inhibitors, a new class of cyclic peptide CXCL12-based CXCR4 inhibitors was discovered (IT Patent M12010A 000096; PCT WO2011/092575 A1) and validated for efficacy in in vitro and in vivo models. Among the tested peptides RFF-1 showed potent and specific inhibitory effects on CXCR4-mediated functions in multiple in vitro assays (P-ERK induction, migration and calcium mobilization CXCL12-induced and binding to CXCR4). C57/BL mice were injected with B16 melanoma cells transfected with human CXCR4. A 4,5 fold reduction in lung metastases was observed after 10 days treatment with 2 mg/kg intraperitoneally (i.p.) RFF-1 compared to the CXCR4 inhibitor AMD3100 (1.25mg/kg i.p), the powerful CXCR4 inhibitor not suitable for prolonged administration, that reduced lung metastases of about 4 fold. In another model of mouse osteosarcoma, K7M2 murine cells, were injected in Balb/C mice. A 3 fold reduction in lung metastases was observed after 15 days treatment with 10 mg/kg i.p. RFF-1 whereas AMD3100 treatment (2.5mg/kg i.p.) lead to 1.8 fold increase in lung metastases. Additionally, a 30% reduction in primary cell growth was achieved in a subcutaneous model of human renal cancer SN12C cells when i.p. treated with 2 mg/kg RFF-1. With the aim to evaluate RFF-1 efficacy in hematopoietic stem cell (HSC) mobilization DBA/2 healthy mice were injected with a single s.c. RFF-1 dose and peripheral blood HSC mobilization was evaluated by colony forming unit assay. Treatment with 30 mg/kg RFF-1 results in rapid, potent and durable mobilization of HSC reaching faster the peak compared to 20 mg/kg AMD3100. These results have prompted us to pursue the clinical development of peptide RFF-1. A first in human Phase I trial is planned to determine the maximal tolerated dose and recommended Phase 2 dose, toxicity profile, pharmacokinetics and antitumor activity of RFF-1 in patients with refractory solid tumors. The Phase I-II study of a novel CXCR4 antagonist provides the opportunity to develop settings in diseases where there is increasing evidence of a role for CXCR4 in the development and progression of metastases such as relapsed glioblastoma, neoadjuvant colorectal and breast cancer, and advanced prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4645. doi:1538-7445.AM2012-4645

CFU-GM Capacity, Engraftment, and Long-Term Graft Function: A Comparison of Three Methods of Peripheral Blood Hematopoietic Stem Cell Mobilization (G-CSF, G-CSF + Plerixafor, or Cyclophosphamide + G/GM-CSF) in Patients Receiving Similar CD34+ Cell Doses

The dose of CD34+ cells/kg in the mobilized PBHSC product is regarded as the main determinant of neutrophil and platelet engraftment after AHSCT. Whether the method of HSC mobilization, namely G-CSF alone (G), G-CSF + plerixafor (G+P) or cyclophosphamide + G/GM-CSF (Cy+G/GM), independently affects CFU-GM capacity, engraftment, and graft function is unknown.

Effects of Method of Peripheral Blood Hematopoietic Stem Cell Mobilization (G-CSF, G-CSF + Plerixafor, or Cyclophosphamide + G/GM-CSF) on Engraftment and Sustained Graft Function: Comparison Across Cohorts with Similar CD34+ Cell Dose

AbstractAbstract 2255Effects of Method of Peripheral Blood Hematopoietic Stem Cell Mobilization, G-CSF, G-CSF + Plerixafor, or Cyclophosphamide + G/GM-CSF, on Engraftment and Sustained Graft Function: Comparison Across Cohorts With Similar CD34+ Cell Dose. Introduction:Autologous peripheral blood hematopoietic stem cell transplantation (AHSCT) is a key therapeutic modality in the management of multiple myeloma (MM) and lymphomas (Ly). The dose of CD34+ cells/kg in the mobilized peripheral blood product has long been regarded as the main determinant of neutrophil and platelet engraftment after AHSCT. Whether the method of hematopoietic stem cell mobilization, namely G-CSF alone (G), G-CSF + plerixafor (G+P) or cyclophosphamide +G/GM-CSF (Cy+G/GM) independently affects engraftment and graft function is unknown. Method:We used a database of AHSCT patients with MM or Ly to define 3 groups with different mobilization strategies (G, G+P, Cy+G/GM) but receiving similar CD34+ cell doses. Mobilization strategies had been determined by the standard practice at the time of the transplant (Cy + G/GM) or, more recently, by an algorithm factoring in the target CD34+ cell dose and the peripheral blood CD34+ count after 4 days of G-CSF mobilization (G and G+P). Imbalances in cell doses across the three groups were resolved by eliminating from the analysis patients with extremes of CD34+ doses (without investigator awareness of the engraftment endpoints) so all groups had similar averages and variation in CD34+ doses. The three groups were compared in terms of engraftment of neutrophils (defined as the first of 3 consecutive days with neutrophil count >500/mm3) and platelets (first of 3 consecutive days with platelet count >20,000/mm3 without transfusion). Comparisons of sustained graft function were based on total white blood cell count, absolute neutrophil count, and platelet count on or near day 100 after transplantation. All patients received G-CSF support after transplantation at 10 mcg/kg/day from day 7 until neutrophil engraftment. Results:The initial database contained 123 (70 MM and 53 Ly) patients undergoing transplantation in the three groups (26 G, 38 G+P and 59 Cy+G/GM). The average (+/− SD) cell doses (×106 CD34+/kg) were 4.56 +/−1.85, 5.3 +/−3.07 and 6.63+/−4.31 in G, G+P and Cy+G/GM respectively. After elimination of patients with extremes of CD34+ dose to correct imbalances, 99 patients remained in the analysis (26 G, 33 G+P and 40 Cy+G/GM), defining three groups with similar average and distribution of cell doses. Average cell doses and endpoints are shown in the table. There were no statistically significant differences in time to neutrophil engraftment across the three groups. Platelet engraftment was significantly slower in G+P (16.2 +/− 8.2 days) than in G (12.7 +/− 3.3) or Cy+GM (11.7 +/− 8.2; ANOVA P=0.03). There were no significant differences on day 100 total white blood cell count, absolute neutrophil count or platelet count among the three groups. Conclusions:Mobilization with G+P may lead to delayed platelet engraftment independently of CD34+ cell dose. Whether this effect is determined by plerixafor itself or by pre mobilization factors associated with plerixafor use remains to be determined. Day 100 graft function is not affected by mobilization strategy.Mobilization StrategiesPG (n=26)G+P (n=33)Cy+G/GM (n=40)CD 34+ cell dose (× 106/kg)4.57 +/− 1.854.83 +/− 1.944.67 +/− 1.03Neutrophil engraftment (days)12.9 +/− 2.614.2 +/− 4.012.9 +/− 3.60.23Platelet engraftment (days)12.7 +/− 3.316.2 +/− 8.211.7 +/− 8.20.03D100 white blood cell count(103/mm3)5.23 +/− 2.114.57 +/− 1.75.25 +/− 2.070.37D100 neutrophil count (103/mm3)3.17 +/− 1.492.6 +/− 1.053.27 +/− 1.870.23D100 platelet count (103/mm3)136 +/− 56154 +/− 66156 +/− 820.63 Disclosures:No relevant conflicts of interest to declare.

Herpes Zoster Infection Associated with Poor Peripheral Blood Hematopoietic Stem Cell Mobilization

The efficacy of peripheral blood hematopoietic stem cell (PBSC) harvest is important for successful autologous transplantation. The impact of viral infection on PBSC mobilization has rarely been reported. Here, we report a patient with relapsed diffuse large B-cell lymphoma who experienced disseminated cutaneous herpes zoster infection during the neutropenic phase of PBSC mobilization. A markedly reduced number of PBSCs was initially harvested (1.72 x 10(6)/kg, 77.2% reduction), followed by a sufficient number (7.55 x 10(6)/kg) during remobilization with the same mobilization regimen when herpes zoster infection had subsided. Because of the temporal association, we suggest that herpes zoster infection is a risk factor for poor PBSC mobilization, and remobilization with the same regimen is feasible.

Peripheral blood hematopoietic stem cell mobilization and collection efficacy is not an independent prognostic factor for autologous stem cell transplantation

The successful mobilization and collection of hematopoietic stem cells are dependent on a number of clinical factors such as previous chemotherapy and disease stage. The aim of this retrospective study was to determine whether the effectiveness of mobilization and collection is an independent prognostic factor for autologous stem cell transplantation outcome. A total of 358 patients who received transplants from January 2003 to December 2004 (201 male and 157 female patients, ages from 2.7 to 77.3 years with median of 53 years of age) underwent autologous hematopoietic stem cell collection after mobilization with granulocyte-colony-stimulating factor (G-CSF) or G-CSF plus chemotherapy priming. This retrospective study included patients with diagnoses of acute myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, and solid tumors. All patients underwent stem cell collection until a target or a minimum CD34+ cell dose was reached. Correlations were performed between stem cell mobilization and/or collection efficacy and transplantation outcomes. In general, both larger reinfused CD34+ cell dose and shorter number of days for the stem cell count to reach the minimum of 2 x 10(6) per kg CD34+ cells do not foster quicker engraftment. Reinfused CD34+ cell dose of less than 12 x 10(6) and number of days stem cell collection to reach this minimum CD34+ cell dose did not independently affect the overall survival (OS) or disease-free survival (DFS). The effectiveness of hematopoietic stem cell mobilization and collection as defined as number of days to reach a CD34+ cell dose of 2 x 10(6) per kg should not be used independently to forecast posttransplantation prognosis, engraftment, DFS, and OS.