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4.
Transfus Apher Sci ; 63(3): 103934, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38678982

RESUMEN

Autologous hematopoietic progenitor cell transplantation (ASCT) has been used for more than five decades to treat malignant and non-malignant diseases. Successful engraftment after high-dose chemotherapy relies on the ability to collect sufficient CD34 + hematopoietic progenitor cells (HPCs), typically from peripheral blood after mobilization. Commonly, either granulocyte colony-stimulating factor (G-CSF) alone as a single agent (i.e. steady-state mobilization) or G-CSF after chemotherapy is administered to collect adequate numbers of HPCs (minimum ≥2 × 106 CD34 + cells/kg for one ASCT; optimal up to 5 × 106 CD34 + cells/kg). However, a significant proportion of patients fail successful HPC mobilization, which is commonly defined as a CD34+ cell count below 10-15/µL after at least 4 days of 10 µg/kg b.w. G-CSF alone, or after chemo-mobilization in combination with 5-10 µg/kg b.w. G-CSF. In these situations plerixafor, a chemokine receptor inhibitor (CXCR4) can be used to enhance HPC collection in patients with multiple myeloma and malignant lymphoma whose cells mobilize poorly. Risk factors for poor mobilization have been evaluated and several strategies (e.g. plerixafor to rescue the mobilization approach or pre-emptive use) have been suggested to optimize mobilization, especially in patients at risk. This manuscript discusses the risk factors of poor CD34+ mobilization and summarizes the current strategies to optimize mobilization and HPC collection.


Asunto(s)
Movilización de Célula Madre Hematopoyética , Humanos , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Ciclamas/farmacología , Ciclamas/uso terapéutico , Bencilaminas
5.
Cells ; 13(7)2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38607025

RESUMEN

Achieving successful hematopoietic stem cell transplantation (HSCT) relies on two fundamental pillars: effective mobilization and efficient collection through apheresis to attain the optimal graft dose. These cornerstones pave the way for enhanced patient outcomes. The primary challenges encountered by the clinical unit and collection facility within a transplant program encompass augmenting mobilization efficiency to optimize the harvest of target cell populations, implementing robust monitoring and predictive strategies for mobilization, streamlining the apheresis procedure to minimize collection duration while ensuring adequate yield, prioritizing patient comfort by reducing the overall collection time, guaranteeing the quality and purity of stem cell products to optimize graft function and transplant success, and facilitating seamless coordination between diverse entities involved in the HSCT process. In this review, we aim to address key questions and provide insights into the critical aspects of mobilizing and collecting hematopoietic stem cells for transplantation purposes.


Asunto(s)
Eliminación de Componentes Sanguíneos , Trasplante de Células Madre Hematopoyéticas , Adulto , Humanos , Movilización de Célula Madre Hematopoyética/métodos , Trasplante Homólogo , Eliminación de Componentes Sanguíneos/métodos , Células Madre Hematopoyéticas
6.
Pediatr Transplant ; 28(3): e14751, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38659194

RESUMEN

BACKGROUND: The published experience concerning autologous peripheral blood stem cell collection in children is very limited. METHODS: The data of pediatric patients who underwent autologous stem cell mobilization and apheresis between January 2011 and April 2020 were analyzed retrospectively. RESULTS: We studied retrospectively 64 mobilization and apheresis procedures in 48 pediatric patients (34 males, 14 females), mean age of 7.31 ± 5.38 (range, 1.5-19.7) years, the underlying disease was mostly neuroblastoma (NBL). The body weight of 21 patients (43.75%) was 15 kg or less. The targeted autologous peripheral stem cell apheresis (APSCA) was successfully achieved in 98% of patients. Neuroblastoma patients were younger than the rest of the patients and underwent apheresis after receiving fewer chemotherapy cycles than others and all of them mobilized within the first session successfully. Plerixafor was added to mobilization in nine heavily pretreated patients (18.7%), median two doses (range, 1-4 doses). 11 patients (22.9%) underwent radiotherapy (RT) before mobilization with doses of median 24 Gy (range, 10.8-54.0 Gy). Patients with RT were older at the time of apheresis and had received more chemotherapy courses than patients without RT. As a result, patients with a history of RT had significantly lower peripheral CD34+ cells and CD34+ yields than those without RT. In 17 patients (35.4%), 22 different complications were noted. The most common complications were catheter-related infections (n:10, 20.8%), followed by catheter-related thrombosis in eight patients (16.7%). CONCLUSIONS: Patients who had far less therapy before apheresis were more likely to mobilize successfully. Our study provides a detailed practice approach including complications during APSCA aiming to increase the success rates of apheresis in transplantation centers.


Asunto(s)
Eliminación de Componentes Sanguíneos , Movilización de Célula Madre Hematopoyética , Neoplasias , Trasplante de Células Madre de Sangre Periférica , Trasplante Autólogo , Humanos , Femenino , Masculino , Movilización de Célula Madre Hematopoyética/métodos , Niño , Estudios Retrospectivos , Preescolar , Adolescente , Lactante , Eliminación de Componentes Sanguíneos/métodos , Trasplante de Células Madre de Sangre Periférica/métodos , Neoplasias/terapia , Adulto Joven , Células Madre de Sangre Periférica
7.
Transfusion ; 64(5): 871-880, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38600674

RESUMEN

BACKGROUND: Despite recent advances in the treatment of multiple myeloma, high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) remains an essential therapeutic keystone. As for the stem cell mobilization procedure, different regimens have been established, usually consisting of a cycle of chemotherapy followed by application of granulocyte-colony stimulating factor (G-CSF), although febrile neutropenia is a common complication. Following national guidelines, our institution decided to primarily use G-CSF only mobilization during the COVID-19 pandemic to minimize the patients' risk of infection and to reduce the burden on the health system. STUDY DESIGN AND METHODS: In this retrospective single-center analysis, the efficacy and safety of G-CSF only mobilization was evaluated and compared to a historic control cohort undergoing chemotherapy-based mobilization by cyclophosphamide and etoposide (CE) plus G-CSF. RESULTS: Although G-CSF only was associated with a higher need for plerixafor administration (p < .0001) and a higher number of apheresis sessions per patient (p = .0002), we were able to collect the target dose of hematopoietic stem cells in the majority of our patients. CE mobilization achieved higher hematopoietic stem cell yields (p = .0015) and shorter apheresis sessions (p < .0001) yet was accompanied by an increased risk of febrile neutropenia (p < .0001). There was no difference in engraftment after ASCT. DISCUSSION: G-CSF only mobilization is a useful option in selected patients with comorbidities and an increased risk of serious infections, especially in the wintertime or in future pandemics.


Asunto(s)
Ciclofosfamida , Etopósido , Factor Estimulante de Colonias de Granulocitos , Movilización de Célula Madre Hematopoyética , Mieloma Múltiple , Trasplante Autólogo , Humanos , Movilización de Célula Madre Hematopoyética/métodos , Mieloma Múltiple/terapia , Estudios Retrospectivos , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Persona de Mediana Edad , Masculino , Femenino , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Anciano , Etopósido/uso terapéutico , Etopósido/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/métodos , Bencilaminas , COVID-19 , Adulto , Ciclamas/uso terapéutico , Ciclamas/farmacología , SARS-CoV-2 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
8.
Transfus Med Rev ; 38(2): 150824, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38569349

RESUMEN

Limited data regarding elevation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in mobilized donors with G-CSF is available. We extended these findings by examining serum NT-proBNP in a cohort study including 35 healthy donors and 69 patients who received G-CSF for CD34+ mobilization as well as 54 patients who did not receive G-CSF but who underwent collection of CD3+ cells for chimeric antigen receptor (CAR) T-cell manufacturing. No donor in the three cohorts experienced significant cardiac adverse events. NT-proBNP levels were measured before and after G-CSF administration and after finishing apheresis procedure. NT-proBNP increase was observed in mobilized healthy donors after G-CSF administration, but was not observed in mobilized or non-mobilized patients. Only in the cohort of healthy donors, pairwise comparisons using Wilcoxon signed ranks test showed a significant increase between the mean serum NT-proBNP level after G-CSF administration and the mean serum NT-proBNP level measured before G-CSF administration (231.09 ± 156.15 pg/mL vs. 58.88 ± 26.84 pg/mL; P < .01). No correlation was observed between NT-proBNP increase and G-CSF dose (rs = 0.09; n = 32; P = .6) and no other variables contributing to predict serum NT-proBNP increase were detected. In conclusion, we observed a statistically, although not clinically, significant increase of NT-proBNP in healthy donors who received G-CSF as CD34+ cell mobilization.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos , Movilización de Célula Madre Hematopoyética , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Humanos , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Masculino , Factor Estimulante de Colonias de Granulocitos/sangre , Femenino , Movilización de Célula Madre Hematopoyética/métodos , Persona de Mediana Edad , Adulto , Estudios de Cohortes , Anciano , Donantes de Sangre , Antígenos CD34
9.
Ann Med ; 56(1): 2329140, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38470973

RESUMEN

AIM: The combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor is one of the approaches for hematopoietic stem cell mobilization in patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), and Hodgkin's lymphoma (HL). This systematic review and meta-analysis aimed to determine the ability of G-CSF + plerixafor to mobilize peripheral blood (PB) CD34+ cells and examine its safety profile. METHODS: We performed a database search using the terms 'granulocyte colony stimulating factor', 'G-CSF', 'AMD3100', and 'plerixafor', published up to May 1, 2023. The methodology is described in further detail in the PROSPERO database (CRD42023425760). RESULTS: Twenty-three studies were included in this systematic review and meta-analysis. G-CSF + plerixafor resulted in more patients achieving the predetermined apheresis yield of CD34+ cells than G-CSF alone (OR, 5.33; 95%, 4.34-6.55). It was further discovered that G-CSF + plerixafor could mobilize more CD34+ cells into PB, which was beneficial for the next transplantation in both randomized controlled (MD, 18.30; 95%, 8.74-27.85) and single-arm (MD, 20.67; 95%, 14.34-27.00) trials. Furthermore, G-CSF + plerixafor did not cause more treatment emergent adverse events than G-CSF alone (OR, 1.25; 95%, 0.87-1.80). CONCLUSIONS: This study suggests that the combination of G-CSF and plerixafor, resulted in more patients with MM, NHL, and HL, achieving the predetermined apheresis yield of CD34+ cells, which is related to the more effective mobilization of CD34+ cells into PB.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos , Linfoma no Hodgkin , Linfoma , Mieloma Múltiple , Humanos , Movilización de Célula Madre Hematopoyética/métodos , Mieloma Múltiple/terapia , Factor Estimulante de Colonias de Granulocitos , Compuestos Heterocíclicos/efectos adversos , Linfoma/inducido químicamente , Linfoma/terapia , Linfoma no Hodgkin/inducido químicamente , Linfoma no Hodgkin/terapia , Células Madre Hematopoyéticas , Trasplante Autólogo , Bencilaminas , Trasplante de Células Madre Hematopoyéticas/métodos
10.
Curr Opin Hematol ; 31(3): 104-114, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38359264

RESUMEN

PURPOSE OF REVIEW: Gene therapy for sickle cell disease (SCD) is advancing rapidly, with two transformative products recently approved by the US Food and Drug Administration and numerous others under study. All current gene therapy protocols require ex vivo modification of autologous hematopoietic stem cells (HSCs). However, several SCD-related problems impair HSC collection, including a stressed and damaged bone marrow, potential cytotoxicity by the major therapeutic drug hydroxyurea, and inability to use granulocyte colony stimulating factor, which can precipitate severe vaso-occlusive events. RECENT FINDINGS: Peripheral blood mobilization of HSCs using the CXCR4 antagonist plerixafor followed by apheresis collection was recently shown to be safe and effective for most SCD patients and is the current strategy for mobilizing HSCs. However, exceptionally large numbers of HSCs are required to manufacture an adequate cellular product, responses to plerixafor are variable, and most patients require multiple mobilization cycles, increasing the risk for adverse events. For some, gene therapy is prohibited by the failure to obtain adequate numbers of HSCs. SUMMARY: Here we review the current knowledge on HSC collection from individuals with SCD and potential improvements that may enhance the safety, efficacy, and availability of gene therapy for this disorder.


Asunto(s)
Anemia de Células Falciformes , Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos , Humanos , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/uso terapéutico , Compuestos Heterocíclicos/efectos adversos , Células Madre Hematopoyéticas/metabolismo , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/terapia , Factor Estimulante de Colonias de Granulocitos , Terapia Genética/efectos adversos
11.
Blood ; 143(16): 1656-1669, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38295333

RESUMEN

ABSTRACT: Autologous stem cell transplantation (ASCT) is the standard of care consolidation therapy for eligible patients with myeloma but most patients eventually progress, an event associated with features of immune escape. Novel approaches to enhance antimyeloma immunity after ASCT represent a major unmet need. Here, we demonstrate that patient-mobilized stem cell grafts contain high numbers of effector CD8 T cells and immunosuppressive regulatory T cells (Tregs). We showed that bone marrow (BM)-residing T cells are efficiently mobilized during stem cell mobilization (SCM) and hypothesized that mobilized and highly suppressive BM-derived Tregs might limit antimyeloma immunity during SCM. Thus, we performed ASCT in a preclinical myeloma model with or without stringent Treg depletion during SCM. Treg depletion generated SCM grafts containing polyfunctional CD8 T effector memory cells, which dramatically enhanced myeloma control after ASCT. Thus, we explored clinically tractable translational approaches to mimic this scenario. Antibody-based approaches resulted in only partial Treg depletion and were inadequate to recapitulate this effect. In contrast, a synthetic interleukin-2 (IL-2)/IL-15 mimetic that stimulates the IL-2 receptor on CD8 T cells without binding to the high-affinity IL-2Ra used by Tregs efficiently expanded polyfunctional CD8 T cells in mobilized grafts and protected recipients from myeloma progression after ASCT. We confirmed that Treg depletion during stem cell mobilization can mitigate constraints on tumor immunity and result in profound myeloma control after ASCT. Direct and selective cytokine signaling of CD8 T cells can recapitulate this effect and represent a clinically testable strategy to improve responses after ASCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Mieloma Múltiple/patología , Linfocitos T Reguladores , Trasplante de Células Madre Hematopoyéticas/métodos , Movilización de Célula Madre Hematopoyética/métodos , Trasplante Autólogo , Trasplante de Células Madre
12.
Ann Hematol ; 103(5): 1601-1611, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38267561

RESUMEN

High-dose cyclophosphamide (HD-Cy) (3 g/m2) plus granulocyte colony-stimulating factor (G-CSF) is a very effective regimen for peripheral blood stem cell (PBSC) mobilization. Unfortunately, it is associated with an increased risk of neutropenic fever (NF). We analyzed the effect of NF on PBSC apheresis results and the efficacy of prophylactic antibiotics for the prevention of NF associated with HD-Cy plus G-CSF for PBSC mobilization in patients with newly diagnosed multiple myeloma (MM). First, patients were divided into NF ( +) and NF ( -) groups according to whether they suffered from NF during mobilization. Second, we divided patients into an antibiotic prophylaxis group and a nonantibiotic prophylaxis group according to whether antibiotic prophylaxis was used during the mobilization period. Our study showed that NF( +) patients (n = 44) had lower CD34 + cell dose collection (median 2.60 versus 5.34 × 106/kg, P < 0.001) and slower neutrophil engraftment and platelet engraftment (median 11 versus 10 days, P = 0.002, and median 13 versus 11 days, P = 0.043, respectively) than NF( -) patients (n = 234). Of note, the nonantibiotic prophylaxis group patients (n = 30) had a 26.7% incidence of NF. In the patients receiving antibiotic prophylaxis (n = 227), the incidence was reduced to 9.3% (P = 0.01). The antibiotic prophylaxis patients had higher CD34 + cell collection (median 5.41 versus 2.27 × 106/kg, P < 0.001) and lower hospitalization cost of mobilization ($ median 3108.02 versus 3702.39, p = 0.012). Thus, our results demonstrate that NF is associated with lower CD34 + cell collection and that antibiotic prophylaxis can reduce the incidence of NF and improve stem cell mobilization and collection outcomes, which reduces the hospitalization cost of mobilization.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Ciclofosfamida/efectos adversos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Antibacterianos/uso terapéutico , Antígenos CD34/metabolismo
13.
Blood Cells Mol Dis ; 105: 102824, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38262104

RESUMEN

In preparation for hematopoietic stem cell mobilization and collection, current ex vivo gene therapy protocols for sickle cell disease require patients to undergo several months of chronic red cell transfusion. For health care equity, alternatives to red cell transfusion should be available. We examined whether treatment with GBT1118, the murine analog of voxelotor, could be a safe and feasible alternative to red cell transfusion. We found that 3 weeks of treatment with GBT1118 increased the percentage of bone marrow hematopoietic stem cells and upon plerixafor mobilization, the percentage of peripheral blood hematopoietic stem cells. Our data suggest that voxelotor should be further explored for its potential safety and utility as preparation for hematopoietic stem cell mobilization and collection.


Asunto(s)
Anemia de Células Falciformes , Benzaldehídos , Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos , Niacinamida/análogos & derivados , Pirazinas , Humanos , Ratones , Animales , Movilización de Célula Madre Hematopoyética/métodos , Médula Ósea/metabolismo , Células Madre Hematopoyéticas/metabolismo , Compuestos Heterocíclicos/uso terapéutico , Compuestos Heterocíclicos/farmacología , Pirazoles , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/terapia , Anemia de Células Falciformes/metabolismo , Terapia Genética/efectos adversos , Factor Estimulante de Colonias de Granulocitos/farmacología
14.
J Clin Apher ; 39(1): e22102, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38186371

RESUMEN

BACKGROUND: Peripheral blood stem cell (PBSC) collection in children poses challenges due to their small size, low body weight (BW), and unique pediatric physiology, especially among children weighing 20 kg (kg) or less. METHODS: PBSC collection data of both healthy children and patients with thalassemia major (TM) weighing 20 kg or less between January 2013 and December 2020 were reviewed. Moreover, PBSCs characteristics along with various aspects of efficiency and safety between healthy donors and patients with TM were compared. RESULTS: A total of 262 PBSC procedures were performed on 255 children. Of these, 91 procedures were carried out on 85 allogeneic healthy donors, and 171 auto-backup collections were performed on 170 patients with TM to ensure PBSC availability and prevent transplantation failure. A minimum pre-apheresis hemoglobin (HGB) level of 60 g/L was discovered to be safe and feasible in patients with TM. The median CD34+ cell dose in the PBSC product during the initial apheresis procedure was higher in healthy donors compared to patients with TM (7.29 ± 5.28 × 106 cells/kg vs5.88 ± 4.23 × 106 cells/kg, P = .043). The total CD34+ cells/kg recipient weight exhibited a positive correlation with pre-apheresis monocyte counts, but a negative correlation with donor weight. Apheresis significantly reduced hematocrit and platelet counts in the allogeneic group compared to the autologous group. Patients with TM experienced a higher occurrence of bone pain related to granulocyte colony-stimulating factor treatment. Notably, no serious complications related to PBSCs mobilization, central venous catheter placement, or the apheresis procedure were observed in either group. CONCLUSIONS: PBSCs collection was both safe and effective in healthy children and pediatric patients with TM weighing 20 kg or less.


Asunto(s)
Eliminación de Componentes Sanguíneos , Células Madre de Sangre Periférica , Talasemia beta , Humanos , Niño , Talasemia beta/complicaciones , Talasemia beta/terapia , Movilización de Célula Madre Hematopoyética/métodos , Factor Estimulante de Colonias de Granulocitos
15.
Intern Med ; 63(2): 189-195, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-37225486

RESUMEN

Objective Several institutions outsource CD34+ cell counting of leukapheresis products, limiting rapid measurements, as results are obtained the next day. This problem is compounded with plerixafor use, a stem cell-mobilizing drug that increases leukapheresis efficiency but requires administration the day before leukapheresis. Use of this drug for a second leukapheresis procedure before the first-day leukapheresis CD34+ count results are confirmed causes unnecessary leukapheresis and expensive plerixafor administration. We investigated whether or not measuring hematopoietic progenitor cells in leukapheresis products (AP-HPCs) using a Sysmex XN-series analyzer could resolve this problem. Methods We retrospectively compared the absolute AP-HPC value per body weight with the CD34+ (AP-CD34+) count in 96 first-day leukapheresis product samples obtained between September 2013 and January 2021. Comparisons were also conducted according to regimen: granulocyte colony-stimulating factor (G-CSF) monotherapy, chemotherapy plus G-CSF, or plerixafor mobilization. Results AP-CD34+ and AP-HPC counts correlated strongly (rs=0.846) overall and, in particular, under chemotherapy plus G-CSF (rs=0.92) but correlated mildly under G-CSF monotherapy (rs=0.655). AP-HPCs could not completely be dichotomized based on an AP-CD34+ threshold of 2×106/kg for any stimulation procedure. In most cases with AP-HPCs >6×106/kg, the AP-CD34+ count exceeded 2.0×106/kg, but in 5.7% of these cases, the AP-CD34+ count was <2.0×106/kg. A cut-off of AP-HPCs >4.843×106/kg yielded a sensitivity of 71% and specificity of 96% for predicting AP-CD34+≥2×106/kg. Conclusion AP-HPCs can identify cases in which sufficient stem cells have been collected.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos , Trasplante de Células Madre de Sangre Periférica , Células Madre de Sangre Periférica , Humanos , Leucaféresis , Movilización de Célula Madre Hematopoyética/métodos , Células Madre de Sangre Periférica/metabolismo , Estudios Retrospectivos , Trasplante Autólogo , Compuestos Heterocíclicos/farmacología , Compuestos Heterocíclicos/metabolismo , Células Madre Hematopoyéticas/metabolismo , Antígenos CD34/metabolismo , Factor Estimulante de Colonias de Granulocitos/metabolismo
16.
J Clin Apher ; 39(1): e22096, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37937412

RESUMEN

Understanding the apheresis principles for harvesting hematopoietic stem cells (HSCs) is critical for performing efficient procedures. However, despite significant advances in estimating the collection efficiency (CE) of aphereses, many confounding factors still need to be addressed in the classical calculations. The CE values are unrestricted, and many procedures exhibit CEs of a given cell population greater than 100%. This report introduces a simple equation that estimates the "crude" CE, which ranges from 0% to 100% and intrinsically considers the contribution of donor-related variables such as the pre-procedure mobilization and intra-apheresis recruitment of CD34+ cells (as a convenient marker for HSCs), as well as the performance of the apheresis system itself.


Asunto(s)
Eliminación de Componentes Sanguíneos , Trasplante de Células Madre Hematopoyéticas , Humanos , Movilización de Célula Madre Hematopoyética/métodos , Eliminación de Componentes Sanguíneos/métodos , Células Madre Hematopoyéticas , Antígenos CD34 , Donantes de Tejidos
17.
Exp Hematol ; 131: 104147, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38160994

RESUMEN

Hematopoietic stem cell transplantation requires the collection of hematopoietic cells from patients or stem cell donors. Granulocyte colony-stimulating factor (G-CSF) is widely used in the clinic to mobilize hematopoietic stem and progenitor cells (HSPCs) from the adult bone marrow niche into circulation, allowing a collection of HSPCs from the blood. The mechanism by which G-CSF acts to mobilize HSPCs is unclear, with some studies showing a direct stimulation of stem cells and others suggesting that myeloid cells are required. In this study, we developed a heat-inducible G-CSF transgenic zebrafish line to study HSPC mobilization in vivo. Live imaging of HSPCs after G-CSF induction revealed an increase in circulating HSPCs, demonstrating a successful HSPC mobilization. These mobilized HSPCs went on to prematurely colonize the kidney marrow, the adult zebrafish hematopoietic niche. We eliminated neutrophils or macrophages using a nitroreductase-based cell ablation system and found that G-CSF still mobilizes HSPCs from the niche. Our findings indicate that neutrophils and macrophages are not required for G-CSF-induced HSPC mobilization from the embryonic hematopoietic niche.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos , Trasplante de Células Madre Hematopoyéticas , Animales , Humanos , Factor Estimulante de Colonias de Granulocitos/farmacología , Movilización de Célula Madre Hematopoyética/métodos , Pez Cebra/metabolismo , Neutrófilos/metabolismo , Macrófagos/metabolismo
18.
Transfus Apher Sci ; 62(6): 103838, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37925340

RESUMEN

BACKGROUND: Factors such as age, underlying hematological disease, chemotherapy and radiotherapy used, and bone marrow infiltration may cause mobilization failure. Several preclinical observed that diabetes mellitus (DM) leads to profound remodeling of the hematopoietic stem cell (HSC) niche, resulting in the impaired release of HSCs. We aim to examine the effect of DM on HSC mobilization and to investigate whether there is a relationship between complications developing in the DM process and drugs used to treat DM and mobilization failure. METHODS: In Erciyes University Bone Marrow Transplantation Unit, 218 patients who underwent apheresis for stem cell mobilization between 2011 and 2021 were evaluated retrospectively. One hundred and nine patients had a diagnosis of DM, and 109 did not. RESULTS: Mobilization failure developed in 17 (15.6 %) of the patients in the DM group, while it developed in 7 (6.4 %) patients in the non-DM group (p = 0.03). CD34+ stem cell count was 8.05 (1.3-30.2) × 106/kg in the DM group, while it was 8.2 (1.7-37.3) × 106/kg in the other group (p = 0.55). There was no statistically significant relationship between glucose and hemoglobin A1c levels and the amount of CD34+ cells (p = 0.83 and p = 0.14, respectively). Using sulfonylurea was the only independent predictor of mobilization failure (OR 5.75, 95 % CI: 1.38-24.05, p = 0.02). CONCLUSION: DM should be considered a risk factor for mobilization failure. Further research is needed fully to understand the mechanisms underlying the mobilization failure effects of sulfonylureas and to develop strategies to improve stem cell mobilization in diabetic patients.


Asunto(s)
Diabetes Mellitus , Trasplante de Células Madre Hematopoyéticas , Humanos , Movilización de Célula Madre Hematopoyética/métodos , Estudios de Cohortes , Estudios Retrospectivos , Factor Estimulante de Colonias de Granulocitos/farmacología , Antígenos CD34/metabolismo
19.
BMC Cancer ; 23(1): 1132, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37990162

RESUMEN

BACKGROUND: While quadruplet induction therapies deepen responses in newly diagnosed multiple myeloma patients, their impact on peripheral blood stem cell (PBSC) collection remains incompletely understood. This analysis aims to evaluate the effects of prolonged lenalidomide induction and isatuximab- or elotuzumab-containing quadruplet induction therapies on PBSC mobilization and collection. METHODS: A total of 179 transplant-eligible patients with newly diagnosed MM treated at a single academic center were included. The patients were evaluated based on PBSC mobilization and collection parameters, including overall collection results, CD34+ cell levels in peripheral blood, leukapheresis (LP) delays, overall number of LP sessions, and the rate of rescue mobilization with plerixafor. The patients underwent four different induction regimens: Lenalidomide, bortezomib, and dexamethasone (RVd, six 21-day cycles, n = 44), isatuximab-RVd (six 21-day cycles, n = 35), RVd (four 21-day cycles, n = 51), or elotuzumab-RVd (four 21-day cycles, n = 49). RESULTS: The patients' characteristics were well balanced across the different groups. Collection failures, defined as the inability to collect three sufficient PBSC transplants, were rare (n = 3, 2%), with no occurrences in the isatuximab-RVd and elotuzumab-RVd groups. Intensified induction with six 21-day cycles of RVd did not negatively impact the overall number of collected PBSCs (9.7 × 106/kg bw versus 10.5 × 106/kg bw, p = 0.331) compared to four 21-day cycles of RVd. Plerixafor usage was more common after six cycles of RVd compared to four cycles (16% versus 8%). Addition of elotuzumab to RVd did not adversely affect overall PBSC collection (10.9 × 106/kg bw versus 10.5 × 106/kg bw, p = 0.915). Patients treated with isatuximab-RVd (six cycles) had lower numbers of collected stem cells compared to those receiving RVd (six cycles) induction (8.8 × 106/kg bw versus 9.7 × 106/kg bw, p = 0.801), without experiencing significant delays in LP or increased numbers of LP sessions in a multivariable logistic regression analysis. Plerixafor usage was more common after isatuximab plus RVd compared to RVd alone (34% versus 16%). CONCLUSIONS: This study demonstrates that stem cell collection is feasible after prolonged induction with isatuximab-RVd without collection failures and might be further explored as induction therapy. TRIAL REGISTRATION: Patients were treated within the randomized phase III clinical trials GMMG-HD6 (NCT02495922, 24/06/2015) and GMMG-HD7 (NCT03617731, 24/07/2018). However, during stem cell mobilization and -collection, no study-specific therapeutic intervention was performed.


Asunto(s)
Compuestos Heterocíclicos , Mieloma Múltiple , Trasplante de Células Madre de Sangre Periférica , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/uso terapéutico , Lenalidomida/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/diagnóstico , Trasplante Autólogo
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(5): 1403-1409, 2023 Oct.
Artículo en Chino | MEDLINE | ID: mdl-37846691

RESUMEN

OBJECTIVE: To compare the efficacy of plerixafor (PXF) combined with granulocyte colony-stimulating factor (G-CSF) (PXF+G-CSF) and cyclophosphamide (Cy) combined with G-CSF (Cy+G-CSF) in the mobilization of peripheral blood stem cells (PBSCs) in patients with multiple myeloma (MM). METHODS: The clinical data of 41 MM patients who underwent PBSC mobilization using PXF+G-CSF (18 cases) or Cy+G-CSF (23 cases) in Shanxi Bethune Hospital from January 2019 to December 2021 were retrospectively analyzed, including the count of collected CD34+ cells, acquisition success rate, failure rate, and optimal rate. The correlation of sex, age, disease type, DS staging, ISS staging, number of chemotherapy cycle, disease status before mobilization, and mobilization regimen with the collection results was analyzed, and the adverse reactions, length of hospital stay, and hospitalization costs were compared between the two mobilization regimens. RESULTS: The 41 patients underwent 97 mobilization collections, and the median number of CD34+ cells collected was 6.09 (0-34.07)×106/kg. The acquisition success rate, optimal rate, and failure rate was 90.2%, 56.1%, and 9.8%, respectively. Univariate analysis showed that sex, age, disease type, and disease stage had no significant correlation with the number of CD34+ cells collected and acquisition success rate (P >0.05), but the patients with better disease remission than partial remission before mobilization were more likely to obtain higher CD34+ cell count (P <0.05). The PXF+G-CSF group had a larger number of CD34+ cells and higher acquisition success rate in the first collection than Cy+G-CSF group (both P <0.05), and had lower infection risk and shorter length of hospital stay during mobilization (both P <0.05), but the economic burden increased (P <0.05). CONCLUSION: PXF+G-CSF used for PBSC mobilization in MM patients has high first acquisition success rate, large number of CD34+ cells, less number of collection times, and short length of hospital stay, but the economic cost is heavy.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos , Mieloma Múltiple , Células Madre de Sangre Periférica , Humanos , Antígenos CD34/metabolismo , Ciclofosfamida/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Células Madre de Sangre Periférica/metabolismo , Estudios Retrospectivos
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