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Graft-versus-host-disease and granulocyte colony-stimulating factor administration after allogeneic stem cell transplantation

Leukemia volume 19, pages 500–503 (2005)Cite this article

In the last 10 years, the availability of recombinant human granulocyte colony stimulating factors (G-CSF) for hematopoietic stem cell mobilization represented a major advance in the field of allogenic stem cell transplantation (allo-SCT).1, 2 G-CSF-mobilized peripheral blood stem cells (PBSC) have emerged as an attractive alternative to bone marrow (BM) as stem cell source. The first reported case of allogeneic PBSC transplantation in a patient with acute lymphocytic leukemia was published in 1989 by Kessinger et al,3 showing clear evidence of trilineage engraftment. In 1994 and 1995, the first large series of allogeneic transplantation using PBSCs from G-CSF-mobilized donors were reported,4, 5, 6, 7, 8, 9, 10, 11 and the use of allogeneic PBSCs as stem cell source has since rapidly grown in this setting.12 All prospective randomized trials comparing allogeneic PBSCs to BM could confirm that the use of PBSCs is associated with faster hematological recovery. However, these studies have yielded differing results regarding the incidence of acute GVHD and chronic GVHD.13 In an attempt to further improve the outcome after allo-SCT, several prospective clinical trials and retrospective cohort studies examining the safety and efficacy of G-CSF administration after allo-SCT have variably demonstrated beneficial effects, including reductions in time to hematopoietic recovery, transplant-related toxicity, duration of initial hospitalization, and resource utilization.14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 Nevertheless, the understanding of the secondary effects of G-CSF, especially on the immune system, continues to evolve. In addition to in vitro studies evaluating the impact of G-CSF on different effectors of the immune system, recent clinical data suggested that treatment with G-CSF after allo-SCT increases the risk of GVHD and transplant-related death.33 As a matter of fact, these observations are reason for concern.

G-CSF is sometimes used immediately after allo-SCT in an effort to hasten engraftment, thereby reducing complications and morbidities associated with neutropenia. Indeed, serious and life-threatening infectious complications after allo-SCT have been attributed to prolonged neutropenia induced by the myeloablative preparative regimen, and to neutrophil dysfunction in the early phase after transplantation.34, 35 Therefore, in addition to their use to mobilize peripheral blood CD34+ stem cells for autologous transplantation or in healthy donors, it is logical to evaluate hematopoietic growth factors in the early post-transplantation phase to ensure engraftment and to decrease the incidence of hazardous infectious complications. In clinical studies in the autologous transplant setting, it is now well established that administration of G-CSF after graft infusion can significantly shorten the time to neutrophil recovery, reduce days of fever or antibiotic use, and length of hospital stay. The safety and activity of G-CSF have also been evaluated in recipients of allo-SCT. In phase 1 and 2 studies, mild bone pain was the only significant toxicity noted in patients receiving the highest dose level of filgrastim.15, 16, 36 Phase 2 studies with comparison to historical controls have suggested the beneficial effect of filgrastim or lenograstim on neutrophil recovery after allogeneic marrow transplantation.19, 23, 24, 26, 37, 38 These results were confirmed on subset analysis of phase 3 studies of lenograstim after marrow transplantation.20, 39

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Acknowledgements

We thank D Maraninchi and C Mawas for helpful discussions, and for their continuous support. We would like to also thank the ‘Association Sang pour Cent la Vie’ (Paris, France), the ‘Ligue Départementale contre le Cancer du Gard’ (Nimes, France), the ‘Association Méditerranéenne pour le Développement de la Transplantation’ (AMDT, Marseille, France), the ‘Association Laurette Fuguain’ (Paris, France), the ‘Association pour la Recherche sur le Cancer (ARC)’, the ‘Ligue Nationale contre le Cancer’, the ‘Etablissement Français des Greffes (EFG)’ and the GEFLUC for their generous and continuous support for our ongoing basic and clinical research work.

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Authors and Affiliations

  1. Unité de Transplantation et de Thérapie Cellulaire (UTTC), Département d’Hématologie, Institut Paoli-Calmettes, Marseille, France

    M Mohty, C Faucher & D Blaise

  2. Laboratoire d'Immunologie des Tumeurs, Institut Paoli-Calmettes, Marseille, France

    M Mohty

  3. INSERM UMR 599, Marseille, France

    M Mohty & D Blaise

  4. Université de la Méditerranée, Marseille, France

    D Blaise

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Mohty, M., Faucher, C. & Blaise, D. Graft-versus-host-disease and granulocyte colony-stimulating factor administration after allogeneic stem cell transplantation. Leukemia 19, 500–503 (2005). https://doi.org/10.1038/sj.leu.2403660

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