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CD34+ cell responsiveness to stromal cell–derived factor‐1α underlies rate of engraftment after peripheral blood stem cell transplantation
Author(s) -
MarquezCurtis Leah A.,
Turner A. Robert,
Larratt Loree M.,
Letcher Brenda,
Lee Siow F.,
JanowskaWieczorek Anna
Publication year - 2009
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2008.01937.x
Subject(s) - cd34 , progenitor cell , granulocyte colony stimulating factor , bone marrow , homing (biology) , stromal cell , stem cell factor , transplantation , stem cell , haematopoiesis , immunology , andrology , cxcr4 , stromal cell derived factor 1 , leukapheresis , biology , medicine , cancer research , chemokine , microbiology and biotechnology , inflammation , chemotherapy , ecology
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) × 10 6 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.