A comparison of the incidence of the myelodysplastic syndrome and acute myeloid leukaemia following melphalan and cyclophosphamide treatment for myelomatosis. A report to the Medical Research Council's working party on leukaemia in adults.
Twelve of 648 patients in the Medical Research Council's first two trials in myelomatosis have developed myelodysplasia or acute leukaemia. This corresponds to a 5-year actuarial prevalence of 3% and an 8-year prevalence of 10%. Patients were randomised to treatment with either melphalan or cyclophosphamide and the relative capabilities of these two drugs to cause these conditions were examined as a function of duration of treatment. A significant relationship with length of melphalan treatment was found but no relationship was observed for cyclophosphamide treatment. The amount of melphalan treatment given in various intervals before diagnosis of myelodysplasia or leukaemia was studied and it was found that the amount of treatment in the most recent 3-year period was the most important determinant of risk (P = 0.0001). It is estimated that the risk of haemopoietic neoplasia after 10 years of follow-up is about 3% for each year of melphalan treatment and that much of this risk will occur within three years of the last treatment.
Cuzick
J
J
Erskine
S
S
Edelman
D
D
Galton
D A
DA
D000368:Aged; D002986:Clinical Trials as Topic; D003520:Cyclophosphamide / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced*; D008297:Male; D008558:Melphalan / Q000009:adverse effects*; D008875:Middle Aged; D008954:Models, Biological; D009101:Multiple Myeloma / Q000188:drug therapy*; D009190:Myelodysplastic Syndromes / Q000139:chemically induced*; D011897:Random Allocation; D012306:Risk; D013997:Time Factors
D003520:Cyclophosphamide; D008558:Melphalan