INTRODUCTION: Systemic light chain (AL) amyloidosis is a plasma cell disorder characterized by the production of amyloidogenic monoclonal light chains and their deposition in vital organs, particularly heart and kidneys. Cardiac involvement usually leads to progressive disfunction and is considered the main prognostic factor in this disease. Early diagnosis and timely administration of treatment, including supportive care, are essential. In this sense, heart transplantation (HT) may be considered in very selected patients with advanced cardiac disease.

METHODS: We retrospectively analyzed a cohort of patients with AL amyloidosis who underwent HT at our institution between January 2000 and April 2025. Data were updated in June 2025, including patients' and disease characteristics, treatment regimens, hematologic and organ response, and survival outcomes.

RESULTS: Ten patients with AL amyloidosis and advanced cardiac involvement received a HT during the study period, seven of whom were referred from other institutions. The median patient age at diagnosis was 49 years old (IQR, 46–51), with an equal sex ratio. Light-chain isotype was lambda in 8 patients (80%), with a median difference between involved and uninvolved serum free light chains of 279 mg/L (range, 12-2384) and median bone marrow plasma cell infiltration of 8% (range, 1-24). All patients presented with symptoms of heart failure at the time of diagnosis and baseline echocardiography revealed an increased wall thickness, with a median interventricular septum of 14.8 mm (range, 13-21), and median left ventricular ejection fraction (LVEF) of 41% (range 15-65). During follow-up, all patients had LVEF over 50% after HT. Revised Mayo Staging data was available in 9 patients and 2 (22%) met criteria for stage III and 5 (55%) for stage IV.

Diagnosis was established by an endomyocardial biopsy in four patients, renal biopsy in two, and rectal biopsy in one patient. Interestingly, subcutaneous fat fine needle aspiration was performed in six patients, being diagnostic in three of them. Extracardiac involvement was present in 7 patients, but was clinically relevant only in two of them, who were not considered eligible for HT at diagnosis. After achieving hematologic and extracardiac organ response, but progressive heart failure, these patients underwent HT at 17 and 25 months after diagnosis. Median time from diagnosis to HT was 5.9 months.

Nine patients (90%) received anti-plasma cell therapy before HT and median time from diagnosis to treatment onset was only 15 days (range, 3-41). One patient underwent an upfront autologous stem cell transplant (ASCT), five patients (55.5%) received VCD (bortezomib, cyclophosphamide and dexamethasone), one bortezomib plus dexamethasone, one daratumumab alone and one combined with VCD. Among them, 8 patients (88.8%) achieved a hematologic response, including 6 complete responses (CR, 66.6%), one very good partial response (VGPR, 11.1%), and 1 partial response (PR, 11.1%). Four patients received high-dose melphalan as consolidation between 6 and 16 months after HT. The remaining four patients have not received ASCT due to renal failure with refractory cytomegalovirus infection, stable hematologic CR, and short follow-up in the last two patients.

Median progression-free survival (PFS) and overall survival (OS) in the entire cohort were 21.3 and 116.5 months, respectively. Performance of ASCT had an impact on PFS (94.1 vs. 16.5 months, p=NS), being significant on OS (27.5 months vs. not reached, p=0.04). Four patients (40%) experienced hematologic progression after HT at a median time of 57.7 months (range, 16.5 – 108.8). Rescue treatment consisted of VCD in two patients and daratumumab alone in another. During follow-up, three patients died: one due to invasive aspergillosis post-transplantation, and the other two due to progressive disease.

CONCLUSION: We observed high quality responses and prolonged survival in AL patients with otherwise extremely poor prognosis. Advanced cardiac involvement remains a major challenge in this disease, but HT should be considered in selected cases. Early anti-plasma cell therapy and supportive care are crucial, as well as consolidation with ASCT after heart transplantation in order to obtain high-quality hematologic responses and better outcomes. Future multicentre studies with larger cohorts are warranted to further support these results.

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2025
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