Melphalan-resistant lymphoblastoid cell lines established from patients with ovarian cancer treated with cross-linking agents.

Lymphoblastoid cell lines (LCLs) were established from 83 patients with ovarian cancer by transformation of peripheral B lymphocytes with Epstein-Barr virus. Comparing the melphalan resistance of different groups of LCLs using the mean Do obtained from clonogenic survival assays, LCLs from melphalan-treated patients were significantly more resistant than LCLs from patients not treated with this drug. However, prior treatment of the patient with ionizing radiation was not associated with increased in vitro resistance of the LCL to this agent. In melphalan-treated patients where LCLs were established serially, the melphalan Do increased after further melphalan treatment in vivo and decreased when no further treatment was given. No correlation was found between age of donor and LCL resistance to any of the above agents. A group of 15 LCLs previously established from non-tumour donors was less resistant to melphalan than the LCLs from patients with ovarian cancer. In a group of 29 patients with advanced disease in whom the clinical response was known, LCL resistance to melphalan appeared to be associated with poor clinical response to cross-linking agents. These results suggest that B cell populations undergo long term, but not necessarily permanent, increases in resistance to melphalan.