Orthotopic Heart Transplant Facilitated Autologous Hematopoietic Stem Cell Transplantation in Light-Chain Amyloidosis
Authors: Kamble Rammurti , Carrum George , Rice Lawrence , McCarthy John J. , Baker Kelty R. , Ramos Carlos A. , Adrogue Horacio , Estep Jerry 
Published: October 2019

Abstract
Abstract 4489
Dominant cardiac involvement by primary systemic amyloidosis (AL) precludes effective AL treatment and is associated with short survival (median survival for stage-III AL= 3–4 months). Three patients who presented with severe cardiac dysfunction as their major AL manifestation underwent orthotopic heart transplantation (OHT) followed by autologous hematopoietic stem cell transplantation (ASCT). The clinicopathological characteristics of these patients form the basis of this report.
Age at AL presentation was 63, 62 and 44 years in 2 females and 1 male. The time from initial symptoms of AL to diagnosis was 12, 24 and 12 months. Diagnosis of cardiac AL was established via endomyocardial biopsy, Congo red staining and immunohistochemistry. Standard work-up for plasma cell dyscrasia included; serum and urine electrophoresis, immunofixation, measurement of serum-free light-chain ratio and bone marrow biopsy. All patients had stage III AL based on cardiac troponin I and NT-pro-BNP. All had end stage heart failure with New York Heart Association class 4 symptoms and developed cardiogenic shock requiring intra-aortic balloon pump support as a bridge to OHT. All were considered unsuitable for ASCT. Initial treatment was with lenalidomide, dexamethasone in two patients while the third received melphalan and dexamethasone. Table -1 shows the timeline of diagnosis and dual transplants.Table-1:Orthotropic cardiac transplantation (OHT) followed by ASCTAge/SexTime to AL diagnosis (months)Organ involvement (months)Time* to OHT (months)Time to ASCT s/p OHT (months)Survival (months)63/F12Heart, Kidney, PN71330+62/F24Heart, Kidney, PN51626+44/M12Heart, Kidney, tongue41314+*Time to OHT from onset of heart failure symptoms, PN= peripheral nerve, F = female, M= male, s/p= status post
ASCT was performed 13, 16 and 13 months after OHT. All 3 patients were on tacrolimus and prednisone at the time of stem cell mobilization and hematopoietic transplant; two patients were also receiving mycophenolate mofetil and valganciclovir. We collected 6.1 and 6.2 × 106/kg CD-34+ cells in 2 days with filgrastim (5 ug/kg, twice, daily) and plerixafor (16 mg/kg based on day- 4 CD-34+ counts) in two subjects. The third initially failed to mobilize but 4.3×106/kg CD-34+ cells were subsequently obtained when she (patient #2) was remobilized with filgrastim and plerixafor 4 weeks after stopping mycophenolate mofetil. The creatinine clearance at the time of high-dose chemotherapy was 36, 30 and 43 ml/minute. All 3 patients received renal adjusted dose of melphalan at 140mg/m2. Mycophenolate mofetil and Valganciclovir were withheld during neutropenia until engraftment. Time to engraftment for neutrophils (ANC of >500/uL x3 days) was 13, 11 and 14 days. Platelets engraftment (untransfused >20 × 109 for 3 consecutive days) occurred in 14, 13 and 16 days. No patients received post-transplant filgrastim. Patients were hospitalized for 17, 18 and 18 days. Renal function remained stable during ASCT and non-hematological toxicity was limited to grade I-II apart from one grade III oral mucositis and colitis. One patient achieved hematologic complete remission (patient#2) while 2 patients had partial response following ASCT. Post OHT and ASCT all patients are alive and well at follow-up of 14, 26 and 30 months from OHT.
OHT should be considered in select patients with dominant cardiac involvement and advanced heart failure to allow subsequent ASCT and improve survival.

Disclosures:
No relevant conflicts of interest to declare.