Autologous Hematopoietic Cell Transplantation in AL Amyloidosis: A Single-Center Experience

BACKGROUND: The front-line treatment in AL amyloidosis includes autologous stem cell transplantation (ASCT) for selected patients. Cardiac involvement determines patient's eligibility and may delay ASCT or compromise patient outcomes.

METHODS: Retrospective analysis of all consecutive patients with AL amyloidosis receiving an ASCT in our hospital between 2008 and 2023, to assess its safety and efficacy to consolidate disease response in these patients.

RESULTS: Thirty-one patients with AL amyloidosis received an ASCT in our center: median age 56 years (IQR 53-63), 18 male (58.1%), light chain lambda in 24 (77.4%) and gamma in 7 (22.6%), 21 (67.7%) also had multiple myeloma (≥10% plasma cells in the bone marrow), and 23 (74.2%) had been referred to us from other hospitals. Patients were classified as Mayo 2012 stages I, II, III and IV in 4 (13.8%), 4 (13.8%), 13 (44.8%) and 8 (27.6%) cases, respectively (2 missing). Most affected organs by AL amyloid were the heart in 25 (80.6%), kidneys in 22 (71.0%), bone marrow in 15 (48.4%) and gastrointestinal in 13 (41.9%). The commonest chemotherapy employed was bortezomib-cyclophosphamide-dexamethasone (17, 54.8%), and 14 patients (45.2%) received a daratumumab-based therapy. Following one (22, 71.0%), two (5, 16.1%), three (3, 9.7%) or four (1, 3.2%) lines of treatment, at the time of ASCT, all patients were in hematological response, including complete response in 22 (71.0%), very good partial response in 5 (16.1%) and partial response in 4 (12.9%). Also, most patients with cardiac involvement (22 out of 25, 88%) reached ASCT in cardiac response, showing an overall marked reduction in NT-proBNP from 3785 pg/mL (IQR 2342.5-7505.5) at diagnosis to 804pg/mL (IQR 185.5-1385) at ASCT (p<0.001). Achieving such response required a longer time from diagnosis to ASCT in patients with cardiac involvement than in those without it (52.3 months, IQR 35.8-77.0, versus 17.9 months, IQR 13-23.2, respectively; p=0.03). Patients were mobilized for transplant with G-CSF, either steady-state (28, 90.3%) or with chemotherapy (3, 9.7%), and seven required mobilization salvage with plerixafor (22.6%), five out of 14 treated with daratumumab (35.7%) and two out of 17 without it (11.7%). Conditioning regimen was melphalan-200 in all patients but one (96.8%). who received melphalan-140. A median of 4.23x10⁶ CD34+ cells/kg (IQR, 3.02-5.10) were infused. Patients were managed by a multidisciplinary team including cardiologists in patients with cardiac involvement, and other specialists. Commonest posttransplant complications were mucositis (93.5%), infections (64.5%), mainly febrile neutropenia without microbiological documentation, and congestive heart failure (32.3%). Two out of seven patients (28.6%) who received G-CSF to accelerate neutrophil engraftment developed engraftment syndrome and recovered from it. Since G-CSF was withdrawn no other patients have developed this complication. Neutrophil and platelet engraftment were reached at a median of 13 days (IQR 12-15) and 12.5 days (IQR 12-14), respectively. Median duration of hospital admission was 21 days (IQR 18-25). Cardiac response remained stable after ASCT (NT-proBNP at 1 year 511.5 pg/mL (IQR, 193.5-1398.5). With a median follow-up of 3.6 years, only six patients had a disease progression, at a median of 8.7 years (CI95%, 4.0- not reached), and only one patient has died, from a secondary myeloid neoplasm, 9.6 years after ASCT.

CONCLUSIONS: ASCT consolidates the hematologic and organic response of patients with AL amyloidosis. In particular, patients with cardiac involvement can be safely brought to ASCT when cardiac response is favorable. A multidisciplinary management is needed. The experience of our center, which receives patients from all over Spain, shows safety and very prolonged sustained responses after ASCT with high rates of overall and progression-free survival.

ACKNOWLEDGMENTS: We would like to acknowledge Dr Isabel Krsnik, who led and inspired the work of our AL Amyloidosis Unit until her recent retirement, and many colleagues from other hospitals in Spain who kindly refer their patients to our Unit.

No relevant conflicts of interest to declare.