1

The Cancer Risk Associated with Ethylene Oxide in the Processing

of Cord Blood

Byron Butterworth, Ph.D.Butterworth ConsultingJohn Chapman, Ph.D.ThermoGenesis Corp.

March 30, 2007

2

Stem Cells in Cord Blood

• Are used to repopulate the bone marrow of chemotherapy patients – a process involving extensive cell division

• Are long lived, continuously dividing cells that create all hematopoietic progenitor cells for the lifetime of the patient

• Absolutely NO mutagenic changes are acceptable that could yield precancerous or cancerous cells

3

Ethylene Oxide (EtO)

• Proposed Sterilant for cord blood processing disposables

• FDA is proposing to allow 5 mg/disposable• EtO is a potent direct-acting, DNA reactive

mutagen and clastogen• Produces lymphoma and/or leukemia in

mice, rats and human beings• Thus, these DNA cancer target sites are

subject to mutagenic attack by EtO

4

Susceptibility Concerns

• Stem cells would be directly exposed to the DNA reactive mutagen EtO during processing– No anatomic barriers or detoxification mechanisms

• Proliferating cells are highly susceptible to mutation induction by DNA reactive agents

• L5178Y cells grown on plastic culture flasks sterilized with EtO result in mutation frequency increases of 6- to 14-fold

5

There is No “Safe” Dose of Ethylene Oxide

• Current FDA guidance would allow concentrations in the range of 30 to 100 g/ml of EtO in cord blood preparations

• No data are available that demonstrate the safety of these concentrations or any concentration of EtO for stem cell exposure

• FDA and EPA cancer risk models recognize no “safe” or “threshold” dose for direct acting mutagens

6

Only Gamma Irradiation or Steam should be allowed for Sterilization

• The cancer risk of ethylene oxide can be eliminated simply by the use of gamma irradiation or steam for the sterilization of all products for cord blood processing and storage

• Units of stored cord blood exposed to ethylene oxide should not be used without the transplant physician being made aware of the exposure

• New labeling for ethylene oxide exposed cord blood units should be considered