Effect in vivo of recombinant GM-CSF on neutropenia and survival in mice treated by high-dose melphalan.
High doses of melphalan cause severe neutropenia and may irreversibly damage hematopoietic stem cells. Treatment of mice with recombinant murine GM-CSF (GM-CSF) for 5 days immediately after 400 micrograms of melphalan did not prevent the severe neutropenia. However, GM-CSF accelerated the neutrophil recovery and reduced the mortality rate during the neutropenic period compared to melphalan-only treated mice. CFU-GM levels measured 6 d after melphalan treatment without GM-CSF were markedly reduced in the bone marrow while being elevated in the spleen. In comparison, GM-CSF further reduced the total CFU-GM population in melphalan-treated mice including the levels in the bone marrow and in the spleen. On d 14 after melphalan, the spleen regained its active CFU-GM production. By d 90, the number of circulating neutrophils, the number of bone marrow CFU-GM and splenic CFU-GM were the same in GM-CSF-treated and -untreated mice. The results suggest that GM-CSF could be used to shorten the neutropenic period and reduce mortality caused by a high dose of melphalan. Though this effect could be at the expense of a temporary reduction in CFU-GM population, GM-CSF did not induce more long-term damage to myelopoiesis than that already caused by melphalan alone.
Sagi
O
O
Institute of Hematology, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Witz
I P
IP
Shaked
N
N
Ramot
B
B
Douer
D
D
D000380:Agranulocytosis / Q000517:prevention & control*; D000818:Animals; D002452:Cell Count; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D008558:Melphalan / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009503:Neutropenia / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000627:therapeutic use; D015996:Survival Rate
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008558:Melphalan