km-2210 and Leukemia--Lymphocytic--Chronic--B-Cell

A 68 year-old-man was first found to have CLL with IgG, kappa monoclonal gammopathy 6 years ago. Bestrabucil (total dose 35,150 mg) was taken orally from August 1989 to December 1989. Etoposide (total dose 23,100 mg) was then orally administered from January 1990 to December 1995. He was then referred to our hospital in January 1996 because of progressive anemia and thrombocytopenia. Peripheral blood showed a WBC of 21,200/microliter with 4% myeloblasts and 79% lymphocytes, Hb 7.9 g/dl and Plt 5 x 10(4)/microliter. The serum level of lysozyme was increased (75.6 micrograms/ml). Bone marrow aspiration disclosed hyper-cellularity with proliferation of the blasts and a monocytoid cell population, which cytochemical studies demonstrated to be of the myelo-monocytic series, thus indicating acute myelogenous leukemia (AML-M4) superimposed on CLL. Surface marker analysis of bone marrow mononuclear cells revealed reactivity for CD 11c, CD13, CD15, CD33, HLA-DR. The karyotype was normal. Southern blot analysis and reverse transcriptase-polymerase chain reaction did not reveal rearrangement of the MLL gene. Complete remission was achieved by chemotherapy consisted of BHAC, idarubicine, 6MP, vincristine and predonisolone. Long-term treatment with oral etoposide may contribute to secondary AML.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chlorambucil; Estradiol; Etoposide; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelomonocytic, Acute; Male; Neoplasms, Second Primary

Busramustine (KM-2210), the benzoate of a 17 beta-estradiol-chlorambucil conjugate, was administered to 11 patients with chronic lymphocytic leukemia (CLL) which included eight cases of B-cell CLL and three cases of T-cell CLL. Four patients had received prior chemotherapy. Busramustine was given orally at an initial daily dose of 50-100 mg continuously, and the dose was modified according to hematological improvement. Two cases of B-cell CLL achieved clinical complete responses, six cases including two of T-cell CLL and four of B-cell CLL achieved partial responses and one case of B-cell CLL achieved improvement. The partial and complete response rate was 72.7%. Four patients showed estrogen receptor activity of CLL cells ranging from 3.5 to 57.5 fmol/mg cytosol protein, but there seemed to be no correlation between the estrogen receptor activity of the CLL cells and the therapeutic effects of busramustine. Toxic effects included diarrhea (2/11) and estrogen-related symptoms including breast pain (4/11), genital bleeding (2/5), gynecomastia (2/6) and loss of libido (2/6). The findings of this preliminary study suggest that busramustine is effective in the treatment of CLL, irrespective of the presence of the estrogen receptor.

Topics: Adult; Aged; Blood Coagulation; Chlorambucil; Estradiol; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Receptors, Estrogen