Exposure of hematopoietic stem cells to ethylene oxide during processing represents a potential carcinogenic risk for transplant recipients.

Stem cells for transplantation are obtained from bone marrow, umbilical cord blood, and peripheral blood. A rare complication of hematopoietic stem cell transplantation is donor cell-derived leukemia (DCL). The donors remain cancer free and the causes of these DCL are unknown. Stem cells must repopulate the bone marrow and then give rise to all hematopoietic cells for the rest of the transplant recipient's life. No procedure is acceptable that might introduce precancerous or cancerous mutations in cells performing such a critical function. Medical disposable sets consisting of bags, tubing sets and freezing containers are used to collect, purify and store stem cells. Sterilization of disposables with ethylene oxide is widespread, even though those sets unavoidably retain residual amounts of ethylene oxide which is a potent, direct-acting mutagen and clastogen that has been demonstrated to induce hematopoietic cancer in mice, rats and human beings. Potential exposure levels to ethylene oxide during processing under proposed US FDA guidelines for residual ethylene oxide would be biologically active and present a significant risk factor for DCL. For direct-acting mutagens, there is no recognized "no effect" dose using currently accepted cancer risk assessment models. The safety concerns with ethylene oxide can be eliminated by the use of alternative technologies including electron beam, gamma irradiation, or steam for the sterilization of all products used for stem cell processing and storage.