Effects of Low-Dose Cytosine Arabinoside Plus Granulocyte-Macrophage Colony-Stimulating Factor and the Changes of Peripheral Blood Lymphocytes and Bone Marrow Clonogenic Assay in Myelodysplastic Syndrome

Ko, Yun Woong; Lee, Seung Tae; Chong, So Young; Min, Yoo Hong; Hahn, Jee Sook

Abstract

BACKGROUND: In vitro data indicate that granulocyte-macrophage colony-stimulating factor (GM-CSF) induces leukemic clonogenic cells to proliferate, thereby enhancing preferentially the cytotoxicity of the cell cycle-specific drug cytosine arabinoside (Ara-C) when compared with normal hematopoietic progenitor cells. We evaluated the therapeutic outcomes of low-dose Ara-C (LD Ara-C) plus GM-CSF for the patients with high-risk myelodysplastic syndrome (MDS). At the same time we evaluated the lymphocyte subset of peripheral blood and the bone marrow clonogenic assay of those patients.
METHODS
Thirteen patients of MDS were treated with combination therapy composed of LD Ara-C and GM-CSF. The proportion of peripheral blood CD4, CD8 T-lymphocytes and natural killer (NK) cells were enumerated by flow cytometric direct immunofluorescence method. Clonogenic assays were done by methylcellulose culture system. Those laboratory parameters were analyzed with regard to the therapeutic responses.
RESULTS
The subtypes according to the FAB classification included 8 patients of refractory anemia with excess of blasts (RAEB), 4 RAEB-transformation (RAEBT) and 1 chronic myelomonocytic leukemia (CMML). Five cases (38.5%) achieved complete remission after this type of treatment, two (15.4%) had a partial remisison and six (46.2%) had no response. The treatment was generally tolerable. There was no early toxic death. The median disease-free survival of the complete responders was 6 months. Three cases had a progression to acute leukemia. The proportion of pre-treatment CD4-positive T-lymphocytes in non-responders was significantly lower than that of complete responders (P<0.05). Eight cases (61.5%) showed "leukemic" growth pattern in clonogenic assay. The proportion of the "nonleukemic" growth in the complete responders was higher than that of nonresponders.
CONCLUSION
The combined treatment of LD Ara-C and GM-CSF was tolerable for the patients with high-risk MDS. The immunologic parameters and in vitro growth pattern were thought to be associated with therapeutic responses. Further studies for the large number of patients will be required.