Can Stem Cell Mobilization Separate GvHD and GvL Effect?

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Blood First Edition Paper, prepublished online December 27, 2005

Submitted October 31, 2005

Accepted December 18, 2005

Stem cell mobilization with G-CSF analogs: A rational approach to

separate GVHD and GVL?

S , Kelli P Mac, and Geoffrey R Hill*

Queensland Institute of Medical Research, Brisbane, QLD, Australia

The separation of GVHD and GVL remains the " holy grail " of allogeneic

stem cell transplantation, and improvements are urgently needed to

allow more effective therapy of malignant disease.

The use of G-CSF mobilized peripheral blood as a clinical stem cell

source is associated with enhanced GVL effects, without amplification

of significant acute GVHD.

Preclinical studies have demonstrated that G-CSF modulates donor T

cell function prior to transplantation, promoting Th2 differentiation

and regulatory T cell function. In addition, the expansion of

immature APC and plasmacytoid DC favors the maintenance of this

pattern of T cell differentiation after transplantation.

Although these patterns of T cell differentiation attenuate acute

GVHD, they do not impact on the cytolytic pathways of the CD8+ T cell

that are critical for effective GVL.

Recently, it has been demonstrated that modification of G-CSF, either

by pegylation of the native cytokine or conjugation to Flt-3L,

results in the expansion and activation of donor iNKT cells, which

significantly augment CD8+ T cell-mediated cytotoxicity and GVL

effects after transplant.

Since these cytokines also enhance the expansion of regulatory T

cells and APC, they further separate GVHD and GVL, offering potential

clinical advantages for the transplant recipient.