High Dose Melphalan Followed By Autologous Stem Cell Transplant in AL Amyloidosis: a Single-Center Experience
Authors: D'Adda Mariella , Schieppati Francesca , Ferrari Samantha , Crippa Claudia , Peli Annalisa , Re Alessandro , Morello Enrico , Tozzi Paola , Orlando Vincenza , Rossi Giuseppe 
Published: October 2019

Abstract
INTRODUCTION: high-dose melphalan (HDM) followed by autologous stem cell transplant (ASCT) has been routinely used as a treatment option for systemic light chain AL amyloisosis since the first report in mid-1990s. The high treatment-related mortality (death before post-transplant day 100) reported in literature (11-40% in different papers) has decreased over the last years with the improvement in patient selection. Particularly, in the largest Mayo Clinic series of 422 subjects, patients with cardiac troponin-T < 0.06 ng/L and NT-proBNP < 5000 ng/L had TRM < 1%; besides, patients achieving hematologic complete response/very good partial remission (CR/VGPR) had superior overall survival than those achieving hematologic partial response (PR) and no response. Here we report our single-center experience of 14 ASCT performed in 10 patients between 2007 and 2014.
PATIENTS AND METHODS: the median age at the time of ASCT was 58 years (range 44-68). Five patients had 2 or more involved organs. All 10 patients had: normal troponin-I value, NT-proBNP < 5000 ng/L, PS 0-1, cardiac ejection fraction over 50%, CO diffusion capacity over 50%; only one had creatinine clearance < 50 ml/min. Three patients collected stem cells after cyclophosphamide (1,5 g/m^2), the others after G-CSF alone. Four patients proceeded directly to ASCT after diagnosis, 3 received CyBorD and 3 other induction regimen (5 patients were non responders and 1 was in hematologic PR after “induction therapy” before HDM). Patients received melphalan 200 mg/m^2 (9 ASCT) or dose adjusted HDM (100-140 mg/m^2, 5 ASCT), depending on clinical decision. Four patients received double ASCT.
RESULTS: median follow up is 48 months (range 0,5-80); all patients were alive at the last visit. Of nine evaluable patients (1 patient too early), overall hematologic and organ response rate after ASCT were 78% and 45%. Only 1 of 4 patients with double ASCT improved response after the second course (this patient maintains a hematologic CR without organ involvement after 80 months of follow up). Median hospitalization for ASCT was 24 days (range 17-45), without any threatening-life side effect. Six of 9 evaluable patients needed a 2ndline therapy for progressive disease after a median follow up of 24 months (range 13-52): 4 of them had achieved hematologic PR after ASCT, 1 patient achieved hematologic VGPR and 1 had no hematologic response. Three patients are in follow up without other therapy after ASCT (2 hematologic CR and 1 non response).
CONCLUSION: HDM followed by ASCT is a very effective treatment option in AL-amyloidosis, which may be effective even in patients non responding to first-line treatment with non myeloablative drugs. According to the data of the literature, our experience suggests that a careful selection of patients is critical for good outcomes and that particular cardiac biomarkers (cardiac troponin-T < 0.06 ng/L and NT-proBNP < 5000 ng/L) are useful to guide the choice of therapy. Furthermore, consolidation therapy (IMiDs and proteasome inhibitors) should be considered for patients who do not obtain at least a VGPR/CR after HDM.

Disclosures
No relevant conflicts of interest to declare.