Granulocyte Colony-Stimulating Factor Priming Before Autologous Bone Marrow Harvest Speeds Up Recovery: Presented at IM
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Granulocyte Colony-Stimulating Factor Priming Before Autologous Bone Marrow Harvest Speeds Up Recovery: Presented at IM

By Crina Frincu-Mallos, PhD

WASHINGTON, DC -- May 27, 2008 -- Priming of marrow-derived stem cells (MSCs) with granulocyte colony-stimulating factor (G-CSF) in patients who fail to mobilise adequate numbers of peripheral blood stem cells (PBSCs) appears to speed up their haematopoietic recovery, according to a study presented here at the 2008 Internal Medicine (IM) Annual Scientific Meeting.

Lead author Gabriel Ghiaur, MD, PhD candidate, Molecular and Developmental Biology Program, Cincinnati Children's Research Foundation and University of Cincinnati, Cincinnati, Ohio, presented the findings in an oral presentation on May 15.

Mobilised PBSCs generated after treatment with G-CSF are currently the preferred source of haematopoietic stem cells for autologous transplantation. However, up to 70% of cancer patients fail to mobilise adequate numbers of PBSCs after chemotherapy (Visani G et al Br J Haematol. 1999;105:775-779).

PBSCs engraft more rapidly compared with marrow-derived stem cells (MSC), possibly due to the effect of G-CSF on engraftment itself, in addition to its known effect on PBSC mobilisation, according to Dr. Ghiaur.

To test this hypothesis, Dr. Ghiaur and colleagues conducted a pilot study on lymphoma patients between 2000 and 2006. A total of 16 patients were accrued in this trial: 12 with non-Hodgkin's lymphoma and 4 with Hodgkin's lymphoma.

All patients were nonmobilisers (ie, they failed to respond to cyclophosphamide/G-CSF mobilisation) and subsequently underwent autologous bone marrow transplantation with G-CSF-primed MSCs, explained Dr. Ghiaur.

Patients were treated with cyclophosphamide at a dose of 2 g/m2/day for 2 days, followed by G-CSF 10 mcg/kg/day. After 1 week, patients in whom adequate PBSCs could not be collected were primed with G-CSF 10 mcg/kg/day for 3 days and MSCs were harvested.

Dr. Ghiaur said that recovery of the absolute neutrophil count was much faster in patients who received G-CSF-primed MSCs compared with those who received G-CSF-nonprimed MSCs (14 days vs 28.5 days). The difference had statistical significance (P = .01).

Similarly, platelet recovery occurred on average at 40 days (range, 19-86 days) for patients receiving G-CSF-primed MSCs, much faster compared with patients receiving G-CSF-nonprimed MSCs, 71 days on average (range, 38-159 days) (P < .05).

The total number of nucleated cells and CD34+ cells infused was similar between the treatment groups, noted Dr. Ghiaur.

"Given the major implications on mortality, morbidity, and financial burden associated with the transplant, these results have prompted the initiation of a multicentre, randomised, phase 3 trial," said Dr. Ghiaur.

The trial will compare 2 graft sources for allogenic transplantation: bone marrow and G-CSF-stimulated bone marrow in children undergoing allogeneic transplantation for leukaemia.

[Presentation title: G-CSF-Priming Prior to Autologous Bone Marrow Harvest for Patients Failing to Mobilize Peripheral Blood Stem Cells. Abstract RP10]

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