Effect in vivo of recombinant GM‐CSF on neutropenia and survival in mice treated by high‐dose melphalan

Orit Sagi, Isaac P. Witz, Nili Snaked, Bracha Ramot, Dan Douer

Research output: Contribution to journalArticlepeer-review

Abstract

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 μg 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.

Original languageEnglish
Pages (from-to)240-244
Number of pages5
JournalEuropean Journal of Haematology
Volume43
Issue number3
DOIs
StatePublished - Sep 1989

Keywords

  • CFU‐GM
  • GM‐CSF
  • melphalan
  • neutropenia

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