Secondary leukaemia and myelodysplasia after autografting for lymphoma: is the transplant to blame?

Haemopoietic stem cell autografting is becoming a standard part of the therapeutic repertoire for salvage of relapsed lymphoma patients. Over the last five years or so a number of studies have identified that such patients are at high risk of developing secondary acute myeloid leukaemia (AML) or myelodysplastic syndromes (MDS). The actuarial risks have been estimated to be up to 18% in some series. More recently, studies from France and the EBMT suggest that in Registries containing large numbers of transplanted patients the risks are lower and are of the order of 3-5% at five years. Cytogenetic examination of bone marrow cells taken pre-transplant may also show identical abnormalities to those found in the leukaemic clone after transplant indicating that in many instances the stem cell damage was caused by prior treatment. In addition, a report from the British National Lymphoma Investigation has identified that post-transplant MDS/AML was related to the total quantity of treatment received, with mustine being identified as a particular culprit. It thus seems probable that the additional stem cell insult offered by the transplant may be small although a factor which may increase the risk is the use of total body irradiation.