Febrile reactions occurring with second cycle of high-dose melphalan and SCT in patients with AL amyloidosis: A 'melphalan recall' reaction

Aggressive treatment with high-dose i.v. melphalan followed by auto-SCT (HDM/SCT) is effective in inducing hematological and clinical remissions, and in extending survival in AL amyloidosis. Tandem cycles of HDM/SCT have been shown to increase hematologic complete response rates in patients with AL amyloidosis. Between April 1994 and July 2008, 57 patients with AL amyloidosis at the Boston University Medical Center were treated with a second cycle of HDM/SCT after failing to achieve a complete response after a first transplantation. A total of 11 of 57 patients (19%) treated with tandem transplantation developed high fever 12-24 h after melphalan administration. The average peak temperature was 39.1 °C. Other clinical features include hypotension, acute renal failure and skin rash. No infectious etiology was identified. One of the patients had serum available for measurement of cytokines before, during and after the febrile reaction. The concentration of several pro-inflammatory cytokines, including IL-6 and TNFα, increased significantly, showing a clear physiological response correlating with the clinical findings. We conclude that an unusual cytokine-mediated febrile reaction can occur in patients with AL amyloidosis exposed to a second cycle of high-dose melphalan, which we have termed a melphalan recall reaction.