Until about ten years ago therapy with courses of prednisolone and melphalan was the standard way of treating this AL type of amyloidosis. When after six courses some effect was observed on the urinary excretion of light chains therapy was continued for one or even two years. One disadvantage of this therapy is that it takes time before the effect on precursor production is high enough to stop ongoing deposition. In this time period amyloid deposition can be progressive leading to progressive organ dysfunction. A second disadvantage is the relatively low chance of effective suppression of the light chain production of this therapy. Therefore clinicians looked for faster and more effective ways of fighting against the monoclonal light chain production.
In the recent years studies have been described in which patients of 65 years or younger were treated with high doses of melphalan followed by autologous peripheral stem cell reinfusion. In The Netherlands many departments of Haematology collaborate (HOVON 41 protocol) to study this high dose melphalan therapy, preceded by three courses of VAD chemotherapy. The results of this high dose melphalan therapy appear to be better than standard therapy with courses of melphalan and prednisolone. However, the immediate risks related to this intensive type chemotherapy are also much higher. Therefore in every individual patient risks and benefits of the different types of therapy should be balanced.This finding of a right balance between risks and benefits is an international challenge. An example of a possible decision tree has recently (January 2004) been published by Martha Skinner from Boston (see scheme). Beside this scheme more information is available to come to a well-balanced choice of therapy in the individual patient with AL amyloidosis. However, the risks of this high dose chemotherapy remain considerable even in experienced centres in highly selected patients.
It is very important to get during therapy an idea of its effectiveness. In this respect two aspects should be studied in the individual patient: the underlying plasma cell dyscrasia and the clinical organ involvement by amyloid deposition. In our AZG hospital we use four categories for clonal response: complete response, partial response, stabilisation, and relapse. For clinical response we use three categories: improvement, stabilisation, and worsening. In this clinical judgement we look at changes in organ involvement (2 or more mm change in ventricular wall thickness, doubling or halving of proteinuria, liver size and alkaline phosphatase, etcetera). Internationally clinicians look for consensus to construct a set of generally accepted criteria of clonal and clinical responses in AL amyloidosis.
van Gameren II, Lokhorst H, Hazenberg BPC, Vellenga E. Therapeutic options in systemic AL amyloidosis. Neth J Med 2004; 62: 106-13 > pdf >
van Gameren II, Hazenberg BPC, Jager PL, Smit JW, Vellenga E. AL amyloidosis treated with induction chemotherapy with VAD followed by high dose melphalan and autologous stem cell transplantation. Amyloid 2002; 9:165-74