Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) administration after autologous bone marrow transplantation for acute myeloblastic leukemia enhances activated killer cell function and may diminish leukemic relapse
Richard, C.; Baro, J.; Bello-Fernandez, C.; Hermida, G.; Calavia, J.; Olalla, I.; Alsar, M.J.; Loyola, I.; Cuadrado, M.A.; Iriondo, A.
Bone Marrow Transplantation 15(5): 721-726
1995
ISSN/ISBN: 0268-3369 PMID: 7670401 Document Number: 448440
Leukemic relapse is the major complication following autologous bone marrow transplantation (BMT) in acute myeloblastic leukemia (AML). Previously, we have shown that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) infusion after autologous BMT has the ability to augment endogenous activated killer (AK) cell function which may play a role in the eradication of minimal residual disease. However, the clinical application of rhGM-CSF in patients with AML has been limited by its potential stimulatory effect on the malignant clone. Here we report the effect of rhGM-CSF 5 mu-g/kg/day infusion on AK cell function in 20 patients with AML undergoing autologous BMT. AK cell function was investigated before autologous BMT, during rhGM-CSF therapy and after withdrawal. In addition, its influence on the actuarial risk of relapse is analyzed and compared with a historical control group of 20 patients transplanted immediately before initiation of this study. rhGM-CSF significatively enhanced AK cell function. During rhGM-CSF treatment, median AK cell function rose from 1.8% before autologous BMT (range 0-8%) to 35% (range 3-80%) and remained increased after cessation of rhGM-CSF (median 20%; range 0-36%; P lt 0.001). After a median follow-up of 24 months, the actuarial risk of relapse is 37.4% in rhGM-CSF-treated patients compared with 49.5% in controls (P = 0.05). Interestingly, none of the 7 patients with an AK cell activity gtoreq 20% in the first 2-5 weeks after autologous BMT have relapsed compared with 6 of 9 patients with an AK cell activity lt 20% (P lt 0.02). These data suggest that patients with AML undergoing autologous BMT and treated with rhGM-CSF may develop in vivo high levels of AK cell function in the early period after autologous BMT. Thus, immunomodulatory effects may contribute to a lower relapse rate. These results warrant a randomized study using rhGM-CSF in patients with AML under in autologous BMT.