In vivo administration of recombinant human granulocyte/macrophage colony-stimulating factor in acute lymphoblastic leukemia patients receiving purged autografts.
Based on the recent reports that recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) accelerates the rate of engraftment in a variety of autologous bone marrow transplantation settings, we have investigated its effects on hematopoietic recovery of patients with acute lymphoblastic leukemia (ALL) undergoing autologous bone marrow transplantation. Our studies, which involved 25 autologous ALL recipients who received rhGM-CSF and 27 controls similar for disease status (remission or relapse) and disease type (B- or T-lineage) differed from previous studies in one important aspect: the bone marrows were purged with 4-hydroperoxcyclophosphamide (4HC) and anti-T or anti-B-cell lineage-specific antibodies before transplantation. Such treatments frequently lead to a reduction in the CFU-GM content of the transplanted marrow. Eighteen of 25 patients completed the entire course of rhGM-CSF. Of the 16 patients who received greater than or equal to 64 micrograms/M2/d for at least eight days, there were five patients who had an apparent rhGM-CSF response and 11 patients who did not respond. Of the parameters analyzed, only the number of CFU-GM progenitor cells infused per kilogram was significantly associated with an rhGM-CSF response. All patients receiving greater than or equal to 1.2 x 10(4) CFU-GM progenitors per kilogram achieved an absolute neutrophil count (ANC) greater than or equal to 1,000/microL by day 21 and had a greater than 50% decrement in ANC within 48 to 72 hours of discontinuing rhGM-CSF, as contrasted to none of the patients receiving less than or equal to 7.2 x 10(3) CFU-GM progenitors per kilogram.(ABSTRACT TRUNCATED AT 250 WORDS)
Blazar
B R
BR
Department of Pediatrics, University of Minnesota Medical School, Minneapolis 55455.
Kersey
J H
JH
McGlave
P B
PB
Vallera
D A
DA
Lasky
L C
LC
Haake
R J
RJ
Bostrom
B
B
Weisdorf
D R
DR
Epstein
C
C
Ramsay
N K
NK
D016026:Bone Marrow Transplantation; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000009:adverse effects / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000009:adverse effects / Q000627:therapeutic use*; D006410:Hematopoiesis; D006801:Humans; D007945:Leukemia, Lymphoid / Q000628:therapy*; D009894:Opportunistic Infections / Q000150:complications; D011994:Recombinant Proteins / Q000627:therapeutic use; D014182:Transplantation, Autologous
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor