Abstract
Immunoglobulin light chain (AL) amyloidosis is a plasma cell dyscrasia with extracellular protein deposition in various organ systems, including the liver. The natural history of AL amyloidosis with liver involvement has a poor prognosis, with median survival of only 8.5 to 9 months. High-dose melphalan chemotherapy and autologous peripheral blood stem cell transplantation (HDM/SCT) has been shown to result in durable hematologic response and prolonged overall survival in systemic AL amyloidosis. Patients were included who had hepatic involvement and received HDM/SCT from 1998 to 2006. Data was collected with the approval of the Institutional Review Board. Patients receiving HDM/SCT had to meet eligibility criteria to qualify for this aggressive treatment. Stem cells were mobilized using G-CSF alone. Intravenous melphalan was administered at 100–200 mg/m2 over 2 days in divided doses and stem cells were re-infused 24–72 hours after HDM. Liver response was determined by criteria set up by the Consensus Opinion from the 10th International Symposium on Amyloid and Amyloidosis. Sixty-nine patients qualified for this study, including 47 males and 22 females. The median age was 56 years (range, 37–75), median bilirubin was 0.5 mg/dL (range, 0.1 to 5.7), median alkaline phosphatase was 193 U/L (range, 59 to 1243) and the median liver size was 3 cm (range, 0–20cm) below the costal margin. Nine patients (13%) died from treatment-related mortality. The hematologic CR one year after treatment was achieved by 53% (31/58) of evaluable patients. The overall survival was 84% at 1 year and 49% at 5 years, by Kaplan-Meier estimates. Hepatic response occurred in 21% (10/47) at 1 year after HDM/SCT and 40% (12/30) at 2 years after HDM/SCT. In summary, hepatic involvement with AL amyloidosis does not increase treatment-related mortality from HDM/SCT. Hepatic response follows a hematological response and can occur as far as 2 years from HDM/SCT. Forty % of surviving evaluable patients showed remission of their hepatic disease from AL amyloidosis by 2 years.
Pathologic improvement after high-dose melphalan and autologous stem cell transplantation for primary systemic amyloidosis
