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Enhancement of hematopoietic stem cell engraftment by inhibition of CXCL12 proteolysis with sitagliptin, an oral dipeptidyl-peptidase IV inhibitor: A report in a case of delayed graft failure.

Focosi D, Kast RE, Metelli MR, Benedetti E, Galimberti S, Papineschi F, Petrini M

Division of Hematology, Azienda Ospedaliera Universitaria Santa Chiara, via Roma 56, 56100 Pisa, Italy.

Hematopoietic stem cell (HSC) transplantation fails if grafted HSCs fail to find and settle in an appropriate bone marrow niche where they can receive required trophic factors from stromal cells. Since intravenously injected HSCs are known to migrate into the bone marrow mainly in response to gradients of the CXCL12 chemokine, we reasoned that drugs that inhibit catabolism of CXCL12 could eventually increase the CXCL12 gradient and enhance engraftment. dipeptidyl peptidase IV (DPP-IV) catalyzes the first step in CXCL12 degradation, and oral DPP-IV inhibitors, such as sitagliptin, have been recently approved for type II diabetes mellitus. We report here a case of delayed graft failure in a T-cell-depleted (TCD) HSC transplant recipient, which was refractory to both retransplantation and high-dose granulocyte-colony stimulating factor (G-CSF). After beginning sitagliptin therapy our patient showed a sustained neutrophil rise and a reduction in transfusion dependence, which worsened again after drug discontinuation. Since these changes were paralleled by fluctuations in CXCL12 levels in serial peripheral blood samples, we discuss here the potential benefit of this class of drugs.

Published 2 June 2008 in Leuk Res.
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