Orthotopic Heart Transplant Facilitated Autologous Hematopoietic Stem Cell Transplantation in Light-Chain Amyloidosis

Dominant cardiac involvement by primary systemic amyloidosis (AL) precludes effective AL treatment and is associated with short survival. Between January 2009 and June 2015, total of 9 patients who presented with severe cardiac dysfunction as their major manifestation of AL underwent orthotopic heart transplantation (OHT). Four of these 9 patients were able to complete the planned second phase of treatment with autologous hematopoietic stem cell transplantation (ASCT) 13-16 months after OHT. Diagnosis of cardiac AL was established via endomyocardial biopsy, Congo red staining and immunohistochemistry. All patients had end stage heart failure and developed cardiogenic shock requiring intra-aortic balloon pump support (median 20 days, range 10-165) as a bridge to OHT.

The median age at AL presentation was 54 years (42-65) in 4 females and 5 males. At median follow-up of 30 months (1-54) from OHT, 6 (66 %) patients are alive (table-1). Two patients died of post-operative complications at 1 and 7 months post OHT; a 3^rd patient died 36 months after OHT (23 months post ASCT) of AL progression. Four patients received ASCT at median of 13 months (13-16) after OHT. In the remaining 3 patients ASCT was not feasible due; to low DLCO; recently treated disseminated Cryptococcus; or prior ASCT.

All 4 patients with ASCT 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 5.7, 6.1 and 6.2 x 10⁶/kg CD-34⁺ cells in 2 days after filgrastim administration (5 ug/kg, twice, daily) and plerixafor (16 mg/kg based on day- 4 CD-34⁺ counts) in 3 subjects. The fourth patient initially failed to mobilize but 4.3x10⁶/kg CD-34⁺ cells were subsequently obtained after stopping mycophenolate mofetil for 4 weeks. The creatinine clearance at the time of the high-dose chemotherapy given prior to ASCT was 36, 30, 41 and 43 ml/minute. All 4 patients received a renal adjusted dose of melphalan at 140mg/m². Mycophenolate mofetil and valganciclovir were withheld during neutropenia until engraftment. No patients received post-transplant filgrastim. Patients were hospitalized for 17, 18, 18 and 20 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. Two patients achieved hematologic complete remission (patient2&4) while 2 patients had a partial response following ASCT. Post OHT and ASCT 3 patients are alive and well at follow-up of 54, 37 and 52 months.

The strategy of OHT followed by ASCT is therefore feasible in select patients with dominant cardiac involvement and advanced heart failure