Long-Term Outcome of Patients with AL Amyloidosis Treated with High-Dose Melphalan and Stem Cell Transplantation: 19 Year Experience at a Single Center

Treatment of AL amyloidosis with high dose intravenous melphalan and autologous stem cell transplant (HDM/SCT) is effective in inducing hematologic and clinical remissions associated with prolonged survival. We have performed 607 transplants from July 1994 to August 2013 in the Amyloidosis Center at Boston Medical Center. Patients were enrolled in several sequential IRB–approved protocols.

The median age of patients was 57 years (range, 28-80). Treatment-related mortality (TRM), defined as death occurring within 100 days of SCT, was 9% (n=52/607). Additionally, there were 11 deaths during stem cell mobilization and collection (SCMC). No death has occurred since 2005 during SCMC and TRM has improved to 5% (n=12/249). Total of 334 patients (55%) received melphalan at 200 mg/m² and 273 (45%) received melphalan at 100-140 mg/m² per protocol, based upon age and organ function. Hematologic CR, as defined by international consensus criteria, occurred in 40% (n=204/512) of evaluable patients measured at 6-12 months post SCT; by intention-to-treat the CR rate was 34%.  Hematologic CR occurred in 45% (n=131/294) of patients who received 200 mg/m² of HDM compared to 33% (n=73/218) of patients who received 100-140 mg/m² of HDM (X² p=0.02). Hematologic relapse occurred in 40 patients (20%) with CR at a median of 4 years (range, 1.6-12.4). The median OS is 6.7 years with a median follow-up of 4.5 years. The median OS has not been reached for patients achieving a CR but exceeds 12.8 years, compared to 6.0 years for those not achieving CR (log-rank p<0.001). The median OS for patients following hematologic relapse is 3.5 years. Twenty-five % of patients are alive, up to 19 years after undergoing HDM/SCT.

These data highlight the remarkable long-term survival obtained with HDM/SCT in AL amyloidosis. While survival is strongly dependent upon achieving a hematologic CR, the survival of patients who do not achieve a CR and of those who relapse after CR also is notable, suggesting a benefit of treatment. Strategies to improve risk-stratification of patients and reduce TRM, as well as using sequential or combination therapies to increase the CR rate, will likely improve outcomes in the future for patients who just a few years ago were considered to have a rapidly fatal diagnosis.

Figure 1: Overall survival based on achievement of hematologic CR