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Antiapoptotic Effect of Growth Factors in Leukemia

Section of Medicine and the Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, UK

To the Editor:

We have read with great interest the article by Ringden et al,¹ who reported on the risk of graft-versus-host disease (GVHD) and death in patients with acute leukemia receiving granulocyte-colony-stimulating factor (G-CSF) after allogeneic bone marrow (BM) transplantation. In this retrospective analysis, patients received bone marrow or peripheral blood stem cells (PBSC), and were administered phrophylatic G-CSF post-transplantation. An increase in GVHD and treatment-related mortality (TRM) was observed only in patients receiving G-CSF after BM transplantation. Similarly, overall and leukemia-free survival rates were significantly reduced (relative to control risks: 0.59, P < .0001; 0.64, P = .0003, respectively).

The results of this study differ from the recently published meta-analyses examining the effect of growth factors on GVHD after allogeneic transplantation.² In addition, as discussed in the accompanying editorial, there were significant differences between the two arms in terms of patient characteristics, GVHD prophylaxis, and disease stage. However, although the authors emphasized the possibility of center effect or bias and discussed their rationale in disregarding interpatient or interstudy variability, no clear hypotheses to explain the negative effects of G-CSF in the GVHD-sensitive cohort were mooted.

There are fundamental differences in the leukocyte profiles of PBSC and BM that need to be considered, which could explain the differences in response to G-CSF. It is already known that 85% of PBSC are composed of granulocytes that undergo apoptosis more readily.³ Therefore, G-CSF would have minimal effects on these cells. Conversely, BM is rich in pluripotent cells highly expressing functional G-CSF receptors, and would respond to the ligand more effectively. This could easily promote the immunogenic cells responsible for the GVHD.

We have recently reported granulocyte-macrophage colony-stimulating factor, a growth factor with similar function and target to G-CSF^4,5 that could potentiate antiapoptotic function in cells expressing the receptor, thereby maintaining the cell viability.⁶ Consequently, it would have been useful to know the G-CSF receptor expression of the bone marrow and PBSCs. It is intriguing to speculate that G-CSF-mediated GVHD was compounded by this feature.

Authors’ Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Ringden O, Labopin M, Gorin NC, et al: Treatment with granulocyte colony-stimulating factor after allogeneic bone marrow transplantation for acute leukemia increases the risk of graft-versus-host disease and death: A study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 22:416-423, 2004[Abstract/Free Full Text]

2. Ho VT, Mirza NQ, Junco D, et al: The effect of hematopoietic growth factors on the risk of graft-vs-host disease after allogeneic hematopoietic stem cell transplantation: A meta-analysis. Bone Marrow Transplant 32:771-775, 2003[CrossRef][Medline]

3. Vasconcelos ZF, Santos BM, Costa ES, et al: T-lymphocyte function from peripheral blood stem-cell donors is inhibited by activated granulocytes. Cytotherapy 5:336-345, 2003[Medline]

4. Gazitt Y: Comparison between granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in the mobilization of peripheral blood stem cells. Curr Opin Hematol 9:190-198, 2002[CrossRef][Medline]

5. Dale DC: Colony-stimulating factors for the management of neutropenia in cancer patients. Drugs 62:1-15, 2002

6. Liu WM, Powles T, Shamash J, et al: Effect of haemopoietic growth factors on cancer cell lines and their role in chemosensitivity. Oncogene 23:981-990, 2004[CrossRef][Medline]

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Related Article

• Treatment With Granulocyte Colony-Stimulating Factor After Allogeneic Bone Marrow Transplantation for Acute Leukemia Increases the Risk of Graft-Versus-Host Disease and Death: A Study From the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation
  Olle Ringdén, Myriam Labopin, Norbert-Claude Gorin, Katarina Le Blanc, Vanderson Rocha, Eliane Gluckman, Jules Reiffers, William Arcese, Jaak M. Vossen, Jean-Pierre Jouet, Catherine Cordonnier, and Francesco Frassoni
  JCO 2004 22: 416-423 [Abstract] [Full Text]

Related Reply

• In Reply:
  Olle Ringdén
  JCO 2005 23: 649-650 [Full Text]
• In Reply:
  Olle Ringdén
  JCO 2005 23: 649-650 [Full Text]

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