Microbial contamination of cellular products for hematolymphoid transplantation therapy: assessment of the problem and strategies to minimize the clinical impact.
BACKGROUND
Hematopoietic progenitor stem cells (HPSC) are a specialized transfusion product used for transplantation. Microbial contamination may occur during harvest or subsequent manipulation of these cells. The same difficulties in ensuring a safe, sterile, final product are faced in the preparation of other cell-therapy products directly obtained from donors. Detection of contamination is problematic, and the clinical significance of infusing contaminated HPSC is controversial.


METHODS
Chimeric Therapies' manufacturing and clinical experience with BM HPSC products and validation of a culture method for detection are described. In addition, this paper reviews the literature concerning contaminated blood products, including rates and circumstances of contamination, organisms, methods of detection, and the clinical significance of infusion of contaminated products.


RESULTS
Seven of 33 BM harvest products received at Chimeric Therapies were culture positive for skin commensal organisms. Three of seven were culture positive in the infused product. This compares with literature reports of 0-42%. No patients had significant infusion reactions or evidence of infection related to the contamination.


CONCLUSIONS
The risks associated with microbial contamination with skin commensals are insignificant compared with other components of transplantation. Contamination with pathogens can be eliminated with careful good manufacturing practices (GMP). A series of practical recommendations are presented for the reduction of contamination in HPSC and cell-therapy products.
Protein Design Labs, Inc., Fremont, CA 94555, USA.
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Whelton
D018929:Cell Culture Techniques / Q000379:methods*; D002469:Cell Separation / Q000379:methods*; D004340:Drug Contamination / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000382:microbiology*; D006801:Humans; D017708:Leukocyte Transfusion / Q000009:adverse effects; D011446:Prospective Studies; D011786:Quality Control; D012867:Skin / Q000382:microbiology