Long Term Survival Analysis after High-Dose Melphalan Chemotherapy Followed by Autologous Stem Cell Transplantation for Treatment of AL Amyloidosis: A Single Centre Experience.

Introduction: AL amyloidosis (AL) is a clonal plasma cell disease with a median survival of 10–14 months without therapy. Phase II studies report remission rates in up to 50% of patients (pts) after high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT). We retrospectively analysed AL pts who underwent HDM and ASCT at the Hammersmith Hospital in London since 1996.

Patients and methods: 19 pts (12 m, 7 f), median age 51 y (40 – 63 y) with lambda (14) or kappa (5) AL (2 pts with multiple myeloma stage IA) had the following leading organ involvements: 10 kidney, 3 cardiac, 3 liver or gut, 3 other. 12 pts had more than 2 involved organs. According to risk criteria for HDM (Comenzo and Gertz, 2002) 12 pts were high, 2 pts intermediate and 5 pts low risk. Stem cells were mobilised with Cyclophosphamide (4 g/m²) in 3 pts, Etoposide (1.6 g/m²) in 1 patient, G-CSF alone in 14 pts, 1 bone marrow harvest was performed. Melphalan dose was: 8 pts 200 mg/m², 5 pts 140 mg/m², 6 pts 100 mg/m². The median number of infused stem cells was 3.45 x 10⁶ CD 34+ /kg bw (1.96 – 11.3 x 10⁶ CD 34+ /kg bw).

Results: Treatment related mortality (TRM) was 26%. In 14 patients who survived longer than 100 days from ASCT 6 pts achieved a haematological remission (5 a complete remission, 1 a partial remission) but in 8 patients no remission was achieved: 2 pts received a second ASCT, 2 pts further chemotherapy, 2 pts required haemodialysis. The mean survival from HDM and ASCT is 58.1 months (SD 9.64 months, 95% CI 39.21 – 76.99). The 1 - year and 2 - years overall survival from HDM and ASCT was 73% and 62%, respectively. The overall survival dropped to 42% after 6 years and the main cause of death was progressive or relapsed AL.

Conclusions: HDM and ASCT is feasible for patients with AL, however, TRM was high at 26% in a group of maily high risk patients. 62% of patients survived longer than 2 years, but disease relapse and deaths from relapsed or progressive disease occurred after longer than 2 years from HDM. Thus, new treatment strategies have to be investigated to treat disease progress and relapse in order to improve the long-term survival after HDM and ASCT in patients with AL.