Single infusion of myeloid progenitors reduces death from Aspergillus fumigatus following chemotherapy-induced neutropenia.
Hematopoietic progenitors committed to the myeloid lineage, the common myeloid and granulocyte-monocyte progenitors (CMP/GMP), have been shown to protect against opportunistic pathogens following myeloablative radiation; however, the efficacy of this approach has not been studied in the setting of chemotherapy-induced neutropenia. In this mouse model, the infusion of CMP/GMP on the day after 5-fluorouracil (5-FU) administration (D+1) resulted in a significant increase in the number of splenic neutrophils by D+8 when compared with 5-FU-only controls (P = .02), the majority of which were CMP/GMP-derived (54%). Moreover, 19% and 28% of neutrophils in the blood and bone marrow, respectively, were CMP/GMP-derived. Survival following intranasal challenge with the fungus Aspergillus fumigatus was significantly higher in CMP/GMP-infused mice than the controls (56% and 33% respectively; P = .019). Thus, a single infusion of CMP/GMP enhances tissue neutrophil content and increases survival against a lethal challenge with A fumigatus in the setting of chemotherapy-induced neutropenia.
BitMansour
Andrew
A
Divisions of Bone Marrow Transplantation and Infectious Diseases, Stanford University Medical Center, H1353, 300 Pasteur Dr, Stanford, CA 94301, USA.
Cao
Thai M
TM
Chao
Stephanie
S
Shashidhar
Sumana
S
Brown
Janice M Y
JM
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001228:Aspergillosis / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D001232:Aspergillus fumigatus; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D023461:Myeloid Progenitor Cells / Q000637:transplantation*; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications* / Q000628:therapy; D009504:Neutrophils / Q000502:physiology; D015996:Survival Rate
D000970:Antineoplastic Agents; D005472:Fluorouracil