Now that a substantial group of
cancer patients has such a favourable prognosis, it has become increasingly important to evaluate the long-term complications of treatment. Of all late effects of treatment, secondary leukaemia is one of the most serious. Increased risk of AML has been observed both after RT and after CT; however, several types of CT have much stronger leukaemogenic properties than RT. Limited field radiation in the therapeutic dose range is associated with very little or no increased risk of leukaemia, which has been attributed to cell killing at the higher radiation doses. With respect to CT, two different syndromes of treatment-related AML have been recognized. Risk of
alkylating agent-related AML is highest in the 5-10 year follow-up period and seems to decrease afterwards. This type of leukaemia is often preceded by MDS, and is characterized by deletions of chromosomes 5 and 7. Leukaemias related to treatment with the
topoisomerase II inhibitors are characterized by a short induction period, presentation as myelomonocytic or monocytic leukaemia (rather than MDS) and balanced
chromosomal translocations involving bands 11q23 and 21q22. This review addresses the risk of secondary AML and MDS following treatment of HD, NHL,
testicular cancer,
ovarian cancer,
breast cancer and paediatric
malignancies. In patients with HD, the risk of AML is higher with an increasing number of
mechlorethamine-
procarbazine-containing cycles, a greater number of CT episodes, and after
splenectomy. The majority of data shows that RT does not add to the leukaemia risk from CT, but this issue is still surrounded by some controversy. ABV(D)-treated patients have a very low risk of AML. Generally, patients with NHL,
testicular cancer and
breast cancer experience much lower risk of AML than patients with HD. NHL and
breast cancer treatment regimens with cumulative
cyclophosphamide doses of 20 g or less do not confer an appreciable increase of AML. Recently, strongly increased AML risk has been observed following autologous
bone marrow transplantation and other dose intensification strategies. Risk factors for this excess remain to be defined. PVB treatment for
testicular cancer is not followed by increased leukaemia risk, but modern
etoposide-containing regimens do confer excess risk, of which the magnitude at conventional
drug doses is not yet well known. High risk of leukaemia has been reported in children treated with epipodophyllotoxins. The leukaemogenic hazards of
cancer treatment should be weighed against their therapeutic benefits.