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-hydroperoxycyclophosphamide (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 ≥ 64 μg/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 ≥ 1.2 x 104 CFU-GM progenitors per kilogram achieved an absolute neutrophil count (ANC) ≥ 1,000/μL by day 21 and had a > 50% decrement in ANC within 48 to 72 hours of discontinuing rhGM-CSF, as contrasted to none of the patients receiving ≤ 7.2 x 103 CFU-GM progenitors per kilogram. The number of CFU-GM progenitor cells infused per kilogram was significantly (P < 0.001) higher in the five patients demonstrating an accelerated neutrophil recovery as compared with the 11 patients without apparent rhGM-CSF benefit (median: 17.5 v 2.0 x 103/kg, respectively), although the number of total marrow cells infused was comparable in the two groups. These studies complement previous reports in demonstrating beneficial effects of GM-CSF on autologous bone marrow engraftment. Moreover, they highlight the need to preserve the CFU-GM content of the marrow in autologous bone marrow transplantation (ABMT) studies in which recombinant growth factors are being tested.
|Original language||English (US)|
|Number of pages||9|
|State||Published - 1989|