Abstract
Background: Autologous stem cell transplantation (ASCT) is considered to be the best method to improve long term survival outcomes in light chain amyloidosis (AL) patients, with a median survival of over 10 years. Crucially, the mortality has decreased over the decades mainly due to refinement of patient selection criteria. Aims: Our aim was to report the changing outcomes of a cohort of UK AL amyloidosis patients treated with ASCT. Methods: All patients with a proven histological diagnosis of amyloidosis and treated with an ASCT from 1994–2018 were identified from our database. Patient baseline characteristics were recorded including biomarker assessment and organ involvement, defined according to international criteria. Haematological response was assessed at six months and organ responses at 12 months, both calculated from the date of the ASCT and defined according to the international amyloidosis consensus criteria. The primary outcome was overall survival (OS), defined as time from ASCT to death. Secondary outcomes included: time to next treatment (TTNT), defined from date of ASCT to the start of next treatment, and transplant related mortality (all-cause mortality before day +100 from return of stem cells). Survival outcomes were analysed using the Kaplan-Meier method, with comparisons done using the log rank test. The Cox proportion hazards model was used to assess predictors of OS. All p-values were two sided and any variable with a P value <0.10 on univariate analysis was included in the multivariate model. Results: Two hundred and sixty four patients were identified. The median age at time of ASCT was 57 years (30–70 years) and the median time from diagnosis to ASCT was 12 (0–263 months). The majority of patients were performance status 0 or 1 (84%). The median number of organs involved was two (range 1–4). The dominant organ involved was kidney (N = 180, 68.2%) with cardiac involvement in 32% (N = 85). The Mayo stage was 1: 44% (N = 63), 2: 39% (N = 56) and 3: 16% (N = 2). Eighty patients (30%) had an up-front ASCT and 45% (N = 118) after first line treatment. Organ response was as follows: cardiac (N = 28, 60.9%), renal (N = 101, 76%) and liver (N = 7, 13.5%). The overall survival post ASCT (OS) was 87 months, (95% CI: 77–106 months) and overall treatment related mortality (TRM) was 8.7%, with a significant reduction over time: 1994–2000: 18.8%; 2001–2006: 13.6%; 2007–2012:6.2%; 2013–2018: 1.1%. A haematological response was achieved in 94.8% of patients and was a strong predictor of both survival (complete response (CR)/very good partial response (VGPR)-139 (95% CI: 82–139 months) vs partial response (PR)/stable disease (SD)/progressive disease (PD)-64 (95% CI: 50–92 months), P = 0.007), see figure, and TTNT (CR/ VGPR: 49 (95% CI: 24–48 months) vs. PR/SD/PD: 35 (95% CI: 9–20 months), P = <0.0001). Mayo stage (P = 0.037) and an abnormal ALP (P = <0.001) were independent predictors of OS on multivariate analysis.Summary/Conclusion: In conclusion this analysis of 264 patients with AL amyloidosis, treated with an ASCT over a 24 year period, confirms excellent long term outcomes and a marked improvement in TRM from 19% to 1% in the latest patient cohort. The median survival in patients achieving a CR response was 11.5 years. Outcomes are now comparable to large transplant centres in the United States. Given this improvement in TRM and long term survival, we confirm that ASCT still remains an important treatment modality for patients with systemic AL amyloidosis.
Published Version
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