Clinical and Laboratory Study of CAG Regimen in Treating AML Subtypes Hard To Cure.

Background and objective: Relapse AML, refractory AML, AML in the old and secondary AML are all AML subtypes hard to cure. They characterize in insensitive to chemotherapy agents, short duration of CR(complete remission), easy to relapse.Yamada et al brought forward CAG regimen, which has been proven effective in treating AML subtypes hard to cure. This regimen can treat these AML subtypes with the CR rate at 62%–86%, media survival of 8–17 months. The adverse reaction of CAG regimen is more moderate than that of standard chemotherapy or salvage therapy. Patients’ life quality gets better when they are treated with CAG regimen. The rationale of CAG regimen is as follows:

1. G-CSF receptors have been reported to be expressed in blastic cells in almost all the patients with AML;

2. CFU-AML can be killed preferentially by prolonged exposure to low dosage of Ara-c in the presence of G-CSF with relative preservation of normal CFU - GM;

3. G-CSF focuses on the precursor of myeloid lineage, the upstream cells are effected slightly;

4. the Acla-mediated cytotoxicity of CFU-AML, which is effective in treating MDR cells, is reported to be enhanced by short-term combination with G-CSF.

There have been few reports published on the mechanism of CAG regimen, especially on the study in vivo. Our study aims to know the process of the CAG regimen functions in vivo by study of clinical use and series of tests.

Methods: Observe the outcome,change of CBC and BM, adverse reaction of 11 AML patients treated with CAG regimen from Jan. 2003 to Apr. 2005. We enrolled 4 patients treated by CAG regimen as study group, 2 patients treated by DA regimen as control group. Mononuclear cells were isolated from heparinized bone marrow samples by Ficoll-Hypaque centrifugation to be conducted morphological observation, livability test, apoptosis index measurement on FCM(PI and Annexin V stain), and clonal culture.

Results:

1. CAG regimen treats AML by means of inducing AML blastic cells synchronous apoptosis, having little effect on normal myeloid cells.

2. We treat 11 patients of AML subtypes hard to cure with CAG regimen from Jan. 2003 to Apr. 2005. CR rate is 27.27%, OR rate is 72.73%. The adverse reaction is moderate.

3. Given the CAG regimen, the count of peripheral WBC rises at first, decreases to the lowest level afterward, then recovers at last. The peak count of WBC of 3 CR cases occurs later than that of other patients, at d4 or d7. While that of NR patients occurs at d2.

4. Ara-c and Acla-mediated cytotoxity on normal myeloid cells and megakaryocyte can be alleviated by G-CSF, thus CAG has little influence on the productivity of myeloid precursors.

CFU-AML can be killed preferentially by CAG regimen in the presence of G-CSF.

Conclusion: CAG regimen treats AML by means of inducing apoptosis with better prognosis and more moderate adverse reaction. We hypothesize that CAG regimen recruits S phase cells and kills them by inducing apoptosis.