This work was supported by an operating grant from the Canadian Blood Services/Canadian Institutes for Health Research Blood Utilization and Conservation Initiative to AJW.
CD34+ cell responsiveness to stromal cell–derived factor-1α underlies rate of engraftment after peripheral blood stem cell transplantation
Article first published online: 2 OCT 2008
© 2008 American Association of Blood Banks
Volume 49, Issue 1, pages 161–169, January 2009
How to Cite
Marquez-Curtis, L. A., Turner, A. R., Larratt, L. M., Letcher, B., Lee, S. F. and Janowska-Wieczorek, A. (2009), CD34+ cell responsiveness to stromal cell–derived factor-1α underlies rate of engraftment after peripheral blood stem cell transplantation. Transfusion, 49: 161–169. doi: 10.1111/j.1537-2995.2008.01937.x
This work was awarded the special recognition of outstanding poster in the cellular therapy category at the 2007 AABB Annual Meeting and TXPO held in Anaheim, CA.
- Issue published online: 23 DEC 2008
- Article first published online: 2 OCT 2008
- Received for publication June 5, 2008; revision received July 30, 2008; and accepted August 5, 2008.
BACKGROUND: Stromal cell–derived factor (SDF)-1, a chemokine produced in the bone marrow (BM), is essential for the homing of hematopoietic stem/progenitor cells (HSPCs) to the BM after transplantation. This study examines whether there is a correlation between the in vitro chemotaxis of CD34+ HSPC toward an SDF-1 gradient and in vivo hematopoietic engraftment.
STUDY DESIGN AND METHODS: Thirty-five patients underwent granulocyte–colony-stimulating factor HSPC collection and autologous transplant with a median dose of 7.7 (range, 3.9-41.5) × 106 CD34+ cells per kg body weight. The chemotactic index (CI) of CD34+ cells isolated from leukapheresis products collected from these patients was calculated as the ratio of the percentages of cells migrating toward an SDF-1 gradient to cells migrating to media alone. Expression of the SDF-1 receptor CXCR4 on CD34+ cells was measured by flow cytometry.
RESULTS: Spontaneous cell migration (range, 3.1 ± 0.6 to 26.5 ± 7.7%) and SDF-1–directed chemotaxis (11.1 ± 0.7 to 54.9 ± 8.3%) of CD34+ cells did not correlate with time to neutrophil engraftment, which occurred at a median of 10 days (range, 8-16 days). Nonparametric tests showed a negative correlation (r = −0.434) between CI and CD34+ cell dose such that neutrophil recovery occurred within the same period in patients transplanted with a lower dose of CD34+ cells but having a high CI as in those transplanted with a higher dose of CD34+ cells but having a low CI. Moreover, CI correlated (r = 0.8) with surface CXCR4 expression on CD34+ cells.
CONCLUSION: In patients transplanted with a relatively lower CD34+ cell dose who achieved fast engraftment, a higher responsiveness to SDF-1 and high CI could have compensated for the lower cell dose. However, to apply the CI as a prognostic factor of the rate of engraftment requires validation in a larger number of patients.