Treosulfan (L-
threitol-1,4-bis-methanesulphonate; Ovastat(R)) is a bifunctional alkylating
drug indicated for the treatment of advanced ovarian
carcinoma. Recent data revealed immunosuppressive characteristics and substantial haematopoietic stem cell toxicity after repeated dosing of mice. Therefore,
treosulfan is considered to be an alternative conditioning agent to
busulfan (for example) administered prior to allogeneic/autologous
stem cell transplantation of patients with haematological
malignancies. An
antineoplastic activity for
treosulfan has been previously shown in preclinical models of
melanoma, breast, lung and
renal-cell carcinomas. Here, in vivo antileukaemic activity of
treosulfan is compared with the activity of equitoxic doses of
cyclophosphamide or
busulfan for the first time using human acute lymphoblastic leukaemia (ALL)-models of paediatric origin xenotransplanted into non-obese diabetic (NOD)/severe combined immunodeficient (SCID) mice.
Treosulfan treatment achieved an optimum treated to control (T/C) value of 159% (survival time) against B-ALL-SCID 7 and a T/C value of 0% (tumour growth) against
T-ALL-SCID 4 and proB-ALL-SCID 19, respectively. Complete regression of established subcutaneously (s.c.) growing nodules of ALL-SCID 4 and 19 was obvious and long-term survivors without tumour re-growth were observed. Equitoxic doses of
busulfan (ALL-SCID 4, 7, 19) or
cyclophosphamide (ALL-SCID 19) were less effective with regard to the numbers of complete regressions and the number of cured animals. Side-effects included myelotoxicity and a small reduction in
body weight, but these were tolerable.
Treosulfan can be considered a highly active antileukaemic
drug whose corresponding clinical value is to be tested in appropriate protocols with leukaemic patients.