Delayed recovery after autologous peripheral hematopoietic cell transplantation: potential effect of a high number of total nucleated cells in the graft.
BACKGROUND
Some patients demonstrate delayed recoveries after autologous hematopoietic stem cell transplantation despite infusion of an adequate number of CD34+ cells/kg and clinically stable status. Factors considered being possible predictors of this outcome in this context were explored.


METHODS
A total of 246 patients were evaluated in terms of engraftment. Delayed recovery was defined by white blood cell recovery time exceeding mean+1 SEM. Clinical factors and graft characteristics were examined. Comparisons between patients with normal or delayed engraftment were made. Proinflammatory cytokines and proteolytic enzyme quantification and CXCR4+ and CD44+ cell enumeration were performed on peripheral hematopoietic stem cells (PHSC) product samples of patients with delayed engraftment and patients with usual engraftment time.


RESULTS
Sixteen patients, who received at least 3 × 10(6) CD34+ cells/kg without known clinical factors likely to affect engraftment, demonstrated a delayed recovery time of over 20 days. Some graft variables were found to be significantly increased in these patients by univariate analysis. One variable was the total number of nucleated cells cryopreserved and infused. Among the nucleated cells, the absolute number of granulocytes before and after cryopreservation also differed significantly between the two groups. A multivariate analysis showed that the main predictive factor for delayed recovery was the number of nucleated cells in the graft (p=0.0044). The influence of contaminating cells might be related to the release of elastase, matrix metalloproteinase-9, interleukin (IL)-1β, and IL-6 involved in stem cell homing.


CONCLUSIONS
Therefore, the numeration of total nucleated cells and granulocytes should be considered as a possible quality control variable of PHSCs submitted for cryopreservation.
Trébéden-Negre
Hélène
H
Department of Biotherapy, Unité de Recherche Clinique, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. helene.trebeden-negre@psl.aphp.fr
Rosenzwajg
Michelle
M
Tanguy
Marie-Laure
ML
Lefrere
François
F
Azar
Nabih
N
Heshmati
Farhad
F
Belhocine
Ramdane
R
Vernant
Jean-Paul
JP
Klatzmann
David
D
Norol
Françoise
F
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D051799:Delayed Graft Function / Q000097:blood / Q000209:etiology*; D005260:Female; D006085:Graft Survival / Q000276:immunology / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D007958:Leukocyte Count; D017708:Leukocyte Transfusion; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020127:Recovery of Function / Q000276:immunology / Q000502:physiology; D014182:Transplantation, Autologous / Q000534:rehabilitation
D018952:Antigens, CD34