The CXCL12-3′A allele is associated with a higher mobilization yield of CD34 progenitors to the peripheral blood of healthy donors for allogeneic transplantation

Bogunia‐Kubik, Katarzyna; Gieryng, Anna; Dłubek, Dorota; Lange, Andrzej

doi:10.1038/bmt.2009.30

Cited by 34 publications

(33 citation statements)

References 23 publications

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“…First evidence of a genetic background determining stem cell mobilization was provided by Benboubker et al [38] who reported an association between the CXCL12-3′A allele and a better mobilization result in healthy stem cell donors. This result could be confirmed by Bogunia-Kubik et al [39] and Ben et al [40]. Martin-Antonio et al [41] reported the same finding and observed associations between mobilization ability and even more polymorphisms, including VCAM-1 und CD44.…”

Section: G-csf Dosing and Factors Affecting Mobilization Efficacysupporting

confidence: 78%

G-CSF in Healthy Allogeneic Stem Cell Donors

Hölig¹

2013

Transfus Med Hemother

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Mobilization of peripheral blood stem cells (PBSC) in healthy volunteers with granulocyte colony-stimulating factor (G-CSF) is currently carried out at many institutions worldwide. This report presents the experience of the Dresden center regarding donor evaluation and mobilization schedule. Data regarding efficacy, short- and long-term safety of G-CSF treatment gained from 8290 PBSC collections in healthy donors are outlined. These results are discussed against the background of the available evidence from the literature. Although established as a standard procedure, G-CSF application to allogeneic donors will always be a very delicate procedure and requires the utmost commitment of all staff involved to ensure maximum donor safety.

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Section: G-csf Dosing and Factors Affecting Mobilization Efficacysupporting

confidence: 78%

G-CSF in Healthy Allogeneic Stem Cell Donors

Hölig¹

2013

Transfus Med Hemother

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“…The association of CXCL12-801A with a higher number of G-CSF-mobilized CD34 + cells has been reported in healthy donors 27 and in patients. 28 The CXCL12/CXCR4 interaction plays an important role in the homing of hematopoietic progenitor cells and their egress to PB during situations of stress.…”

Section: Discussionmentioning

confidence: 99%

“…We also report the effect of G-CSF on a genetic variant in CD44 influencing the number of CD34 + cells collected. We note the influence of a genetic variant in CSFR3 on the number of CD34 + cells mobilized by G-CSF, and that the previously reported association of the CXCL12-801A allele with the number of CD34 + cells after G-CSF administration 27 might be due to a dramatic G-CSF-induced decrease in gene expression in donors with this genetic variant. …”

Section: Cd34mentioning

confidence: 95%

Impact of constitutional polymorphisms in VCAM1 and CD44 on CD34+ cell collection yield after administration of granulocyte colony-stimulating factor to healthy donors

Martín-Antonio¹,

Carmona²,

Falantes³

et al. 2010

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundThe number of CD34 + cells mobilized from bone marrow to peripheral blood after administration of granulocyte colony-stimulating factor varies greatly among healthy donors. This fact might be explained, at least in part, by constitutional differences in genes involved in the interactions tethering CD34 + cells to the bone marrow. Design and MethodsWe analyzed genetic characteristics associated with CD34 + cell mobilization in 112 healthy individuals receiving granulocyte colony-stimulating factor (filgrastim; 10 μg/kg; 5 days). ResultsGenetic variants in VCAM1 and in CD44 were associated with the number of CD34 + cells in peripheral blood after granulocyte colony-stimulating factor administration (P=0.02 and P=0.04, respectively), with the quantity of CD34 + cells ¥10 6 /kg of donor (4.6 versus 6.3; P<0.001 and 7 versus 5.6; P=0.025, respectively), and with total CD34 + cells ¥10 6 (355 versus 495; P=0.002 and 522 versus 422; P=0.012, respectively) in the first apheresis. Of note, granulocyte colonystimulating factor administration was associated with complete disappearance of VCAM1 mRNA expression in peripheral blood. Moreover, genetic variants in granulocyte colony-stimulating factor receptor (CSF3R) and in CXCL12 were associated with a lower and higher number of granulocyte colony-stimulating factor-mobilized CD34 + cells/μL in peripheral blood (81 versus 106; P=0.002 and 165 versus 98; P=0.02, respectively) and a genetic variant in CXCR4 was associated with a lower quantity of CD34 + cells ¥10 6 /kg of donor and total CD34 + cells ¥10 6 (5.3 versus 6.7; P=0.02 and 399 versus 533; P=0.01, respectively). ConclusionsIn conclusion, genetic variability in molecules involved in migration and homing of CD34 + cells influences the degree of mobilization of these cells.

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“…Genetic polymorphism analyses in humans have identified polymorphisms associated with mobilizing response to G-CSF in untranslated regulatory regions of genes encoding GCSFR, adhesion molecules (VCAM-1, CD44), and chemokines (SDF-1), which are all known to regulate HSC trafficking. 108,109 Genetic polymorphisms may predict for poor mobilization, yet it is premature to apply such screenings in the clinic to identify poor mobilizers prospectively. …”

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confidence: 99%

How I treat patients who mobilize hematopoietic stem cells poorly

Levesque

Herbert

2011

Blood

214

235

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Transplantation with 2-5 ؋ 10 6 mobilized CD34 ؉ cells/kg body weight lowers transplantation costs and mortality. Mobilization is most commonly performed with recombinant human G-CSF with or without chemotherapy, but a proportion of patients/donors fail to mobilize sufficient cells. BM disease, prior treatment, and age are factors influencing mobilization, but genetics also contributes. Mobilization may fail because of the changes affecting the HSC/progenitor cell/BM niche integrity and chemotaxis. Poor mobilization affects patient outcome and increases resource use. Until recently increasing G-CSF dose and adding SCF have been used in poor mobilizers with limited success. However, plerixafor through its rapid direct blockage of the CXCR4/CXCL12 chemotaxis pathway and synergy with G-CSF and chemotherapy has become a new and important agent for mobilization. Its efficacy in upfront and failed mobilizers is well established.To maximize HSC harvest in poor mobilizers the clinician needs to optimize current mobilization protocols and to integrate novel agents such as plerixafor. These include when to mobilize in relation to chemotherapy, how to schedule and perform apheresis, how to identify IntroductionHematopoietic stem cell transplantation (HSCT) has revolutionized the curative approach to a number of malignancies and BM failure syndromes by providing hematopoietic and immune rescue after high-dose cytoreductive therapy and, in allogeneic transplantations, graft-versus-tumor effect. [1][2][3][4] The term "mobilization" was first used to describe a 4-fold increase of circulating myeloid progenitors (granulocyte macrophage CFU [CFU-GM]) after the administration of endotoxin to healthy volunteers in 1977. 5 High levels of CFU-GM after recovery from myelosuppressive chemotherapy in humans was first described in 1976. 6 However, it was not until the 1980s that the use of chemotherapy-mobilized HSCs for transplantation was established. [7][8][9] Subsequently, a single high-dose cyclophosphamide was developed as a generic mobilizer. 10 Prof Metcalf led the study that showed the potential of G-CSF in mobilization. 11 Subsequently, 2 Australian centers in Melbourne and Adelaide showed for the first time the use of G-CSF-mobilized HSCs for transplantation, 12 and reports of combined G-CSF and chemotherapy mobilization soon followed. 13 Now, virtually all autologous and three-quarters of allogeneic transplantations are performed with mobilized HSCs (CIBMTR reports). 14,15 The cell dose effect of HSCT describes a threshold of HSCs that, when transplanted, is associated with rapid and sustained blood count recovery. 16 The benefits of rapid recovery are reduced hospitalization, blood product usage, and infections. 12,17 The minimum threshold for autologous transplantation is currently defined as 2 ϫ 10 6 CD34 ϩ cells/kg body weight (BW). 18 Many centers use a minimum of 3 ϫ 10 6 CD34 ϩ cells/kg BW for myeloablative and nonmyeloablative allogeneic and matched unrelated transplantations. Furthermore, Ͼ 5 ϫ 10 6 CD3...

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The CXCL12-3′A allele is associated with a higher mobilization yield of CD34 progenitors to the peripheral blood of healthy donors for allogeneic transplantation

Cited by 34 publications

References 23 publications

G-CSF in Healthy Allogeneic Stem Cell Donors

G-CSF in Healthy Allogeneic Stem Cell Donors

Impact of constitutional polymorphisms in VCAM1 and CD44 on CD34+ cell collection yield after administration of granulocyte colony-stimulating factor to healthy donors

How I treat patients who mobilize hematopoietic stem cells poorly

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