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Bacillus Calmette-Guérin Enhancement of Colony-stimulating Activity and Myeloid Colony Formation following Administration of Cyclophosphamide¹

Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland 20205

Pretreatment of mice with Bacillus Calmette-Guérin (BCG) enhances recovery of the peripheral granulocyte count from cyclophosphamide (CTX)-induced leukopenia. In the present study, in vitro bone marrow culture was used to assess the effect of BCG pretreatment on serum levels of myeloid colonystimulating activity and on regeneration of bone marrow myeloid colony-forming units (CFU-c) following CTX.

C57BL/6 mice received either BCG or 0.9% NaCl solution i.p. 8 days prior to the administration of CTX (300 mg/kg i.p.). Following CTX, peak serum levels of myeloid colony-stimulating activity were strikingly higher in the BCG-pretreated mice [1320 ± 30 (S.E.) units] than in the 0.9% NaCl solution-pretreated mice (764 ± 37 units). BCG pretreatment also resulted in higher numbers of marrow CFU-c during recovery from CTX (e.g., 43.9 ± 1.8 versus 20.0 ± 0.9 myeloid colonies/10⁵ marrow cells, Day 3 post-CTX). However, neither the rate of decline nor the absolute nadir of CFU-c, nor CFU-c cell cycle characteristics were affected by the pretreatment.

The initial effect of i.p. BCG pretreatment on recovery from CTX-induced granulocytopenia is an augmentation of serum myeloid colony-stimulating activity which precedes the enhanced regeneration of CFU-c and the accelerated recovery of the peripheral granulocyte count.

¹ Presented in part at the 1978 Meeting of the American Federation for Clinical Research, May 1, 1978, San Francisco, Calif. (8).

² Present address: Division of Hematology/Oncology, Department of Pediatrics, UCLA Health Sciences Center, Los Angeles, Calif. 90024. To whom requests for reprints should be addressed.

Received 9/25/78. Accepted 4/ 3/79.