GM-CSF therapy for delayed engraftment after autologous bone marrow transplantation.
Based on previous observations that granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes granulocyte recovery following chemotherapy, we evaluated the effect of recombinant human GM-CSF on hematopoietic progenitors and clinical outcome in six patients with delayed engraftment (greater than 55 days) after high-dose therapy and autologous bone marrow transplantation (ABMT). Three patients responded to a 14-day course of GM-CSF (10 micrograms/kg body weight/day) with at least a sevenfold rise in circulating granulocytes and a corresponding increase in granulopoietic activity in the bone marrow. A fourth patient died of infection on the 8th day of GM-CSF therapy with no evidence of response, and the remaining two, one of whom received a lower dose of GM-CSF (5 micrograms/kg/day), did not respond. There was no change in platelet or red cell transfusion requirements in any patient during the treatment. In two of the three responders, the granulocyte counts returned to pretreatment levels by 4 and 7 weeks after stopping the drug, respectively. We observed a marked increase in marrow-derived as well as in circulating granulocyte-macrophage progenitors (granulocyte-macrophage colony-forming units, CFU-GM) by the end of the 14-day course of GM-CSF in the three responders. There was no change in the frequency of circulating or marrow-derived erythroid (erythroid burst-forming units, BFU-E) or multilineage (multilineage colony-forming units, CFU-GEMM) progenitors. The results indicate that GM-CSF therapy in patients with markedly delayed engraftment after ABMT may stimulate granulopoiesis, but the effect is transient in some patients.
Brandwein
J M
JM
University of Toronto Autologous Bone Marrow Transplant Program, Toronto Hospital, Ontario, Canada.
Nayar
R
R
Baker
M A
MA
Sutton
D M
DM
Scott
J G
JG
Sutcliffe
S B
SB
Keating
A
A
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001772:Blood Cell Count / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use* / Q000633:toxicity; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006689:Hodgkin Disease / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008875:Middle Aged; D014182:Transplantation, Autologous
D016178:Granulocyte-Macrophage Colony-Stimulating Factor