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Myeloablative irradiation in non-human primates.

K L Watts¹, B C Beard, B L Wood

¹Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Journal of Medical Primatology

|July 30, 2009

Summary

Total body irradiation (TBI) doses were tested in macaques for cord blood transplantation. A 1200 cGy TBI dose achieved myeloablation with acceptable toxicity, allowing autologous recovery.

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Area of Science:

Primate models in transplantation research
Radiation oncology and dosimetry

Background:

Total body irradiation (TBI) is crucial for conditioning in stem cell transplantation.
Determining optimal TBI doses is essential to balance myeloablation and reduce radiation toxicity.
Pigtailed macaques serve as a relevant preclinical model for human transplantation studies.

Purpose of the Study:

To evaluate varying doses of total body irradiation (TBI) in pigtailed macaques.
To identify an optimal TBI regimen for cord blood transplantation studies.
To assess myelosuppression and radiation-related side effects in macaques.

Main Methods:

Four pigtailed macaques received TBI doses ranging from 800 to 1320 cGy.
Hematopoietic recovery was monitored using complete blood counts (CBC).
Donor cell engraftment was assessed via variable number of tandem repeats (VNTR) analysis.

Main Results:

Macaques receiving 800 or 1020 cGy TBI showed autologous neutrophil recovery within 24 days.
A TBI dose of 1200 cGy resulted in myeloablation without significant extramedullary toxicity.
A higher dose of 1320 cGy TBI led to severe toxicity, requiring study termination.

Conclusions:

Previously considered myeloablative TBI doses can permit autologous recovery in pigtailed macaques.
A TBI dose of 1200 cGy appears optimal for achieving myeloablation while maintaining acceptable non-hematopoietic toxicity.
This finding supports the use of 1200 cGy TBI in macaque models for cord blood transplantation research.