Transplants: ablative or non-ablative?

Continuing from yesterday. Should one go for an ablative or non-ablative transplant? Ablative means using sufficient chemotherapy to destroy as much of the leukemia as possible, while not worrying about how much bone marrow is destroyed because it is going to be replaced by the graft anyway; non-ablative means using immunosuppressive drugs to enable the marrow to engraft and relying on graft-versus-leukemia to destroy the tumor.

The paper in Blood has looked at the results on ablative transplants published by the European Bone Marrow Transplant Registry (EBMTR) and the International BMTR. The long term overall survival was 46% and another 46% died of the treatment (the remaining 8% died of relapsed leukemia). The best results came from the Dana Farber at Boston with only 24% treatment related mortality and 55% overall survival at 6 years. However, none of the Boston patients had fludarabine refractory disease. The median age at transplant ranged between 39 and 48 at different centers.

In the total experience from Europe and America, if an unrelated donor was used, the results were less good, with only 33% overall survival at 5 years.

Non-ablative transplants can be used in older patients - up to 72 years of age, with a median age of between 50 and 57. This type of transplantation is fairly recent, but we do have 7 reports of studies from different units (Seattle, Houston, Boston, Germany, Spain and the UK) on both sides of the Atlantic involving 346 patients.

The degree of myeloablation and immunosuppression varied between centers with Seattle being least for both, Spain being the most myelosuppressive and the UK the most immunosuppressive. Only Seattle has 5-year follow up and they report 23% treatment-related mortality and 50% overall survival similar to Boston's figures on ablative transplants, but 87% of the Seattle patients were refractory to fludarabine and the patients were older. The other studies are less mature, but treatment-related mortality ranged from 16% to 34% and overall survival from 48% to 72%. One suspects that these figures will deteriorate as time passes.

I have interpreted these figures a little. Generally they don't talk about treatment-related mortality, but non-relapse mortality to take account of the fact that some patients commit suicide, others have heart attacks and others are run-down by Greyhound buses. However, most non-relapse deaths are caused by the treatment - even suicides.

One of the reasons that patients commit suicide is that they can't live with chronic graft-versus-host disease. This was least common in those groups treated with more immunosuppressive drugs like alemtuzumab (in the UK) and ATG (in Germany). The worry is that more immunosuppression means more relapses. The data are not mature enough to be sure of this.

So far my conclusions are that about half of CLL patients can expect to be cured by a transplant. Reduced intensity conditioning extends our ability to transplant patients who are older - up to the early seventies - and have co-morbidities. The exact form of conditioning that should be used is still being used, but even among survivors there is a high risk of both acute and chronic graft-versus-host disease which may be very unpleasant.

Transplantation in CLL may justifiably be referred to as a work in progress.