Long Term Outcomes of High Dose Therapy and Autologous Hematopoietic Cell Transplant for Lymphoplasmacytic Lymphoma-Associated Systemic Amyloidosis

Abstract

Background Lymphoplasmacytic lymphoma (LPL) is associated with production of monoclonal paraproteins. Rarely, these paraproteins misfold, aggregate and form amyloid fibrils which deposit in organs and disrupt their structure and function. Several reports have described this association; however, transplant outcomes in patients with LPL and co-existing systemic amyloidosis are not well described. Methods We identified fifty patients with co-existing LPL and systemic amyloidosis diagnosed between 1997 and 2018 who were treated at the Memorial Sloan Kettering Cancer Center. Of these, eight patients underwent high dose therapy (HDT) followed by autologous hematopoietic cell transplant (AHCT) and are subjects of the current study. Results Among the eight patients, the median age was 60 years (range 55-70 years) with 37.5% females. Lymph nodes were the most commonly involved organ (N=6), followed by the heart (N=5), Kidneys (N=4), lungs (N=4) and peripheral nervous system (N=4). Median number of organs involved per patient was 4 (range 1-6). The monoclonal protein was IgM (N=5), IgG (N=2) and free lambda light chain (N=1); lambda light chain was involved in seven of eight patients. Median M spike was 0.43 gm/dL (range 0.2-1.3 gm/dL) and dFLC was 7.93 mg/dL (range 1.89-22.87 mg/dL). All patients had less than 10% plasma cell involvement of bone marrow. Induction regimens varied. Five patients received HDT/AHCT as part of initial therapy and three patients were transplanted at relapse (range 3-6 lines of prior therapy). CD34+ cells were mobilized using GCSF with Plerixafor (N=5), Rituximab, cyclophosphamide and GCSF (N=2) and cyclophosphamide alone (N=1). Median CD34+ cell yield was 8.74 × 106 cells/kg (range 4.5-12.2 × 106 cells/kg). High dose therapy was BCNU, etoposide, Ara-C and melphalan (BEAM) (N=2) and melphalan alone (N=6). Among patients conditioned with melphalan, 3 each received 140 mg/m2 and 200 mg/m2 based on risk adapted dosing. Median number of CD34+ cells infused was 5.325 × 106 cells/kg (range 3.2-5.9 × 106 cells/kg). Hematologic response following HDT/AHCT was very good partial response (VGPR) or better in five of the six patients with long term follow up. At median follow up of 64.5 months (range 3-116 months), all patients were alive at last contact. Only one patient relapsed more than 4 years post-transplant and has responded to salvage Daratumumab. Conclusion Amyloidosis can complicate lymphoplasmacytic lymphoma and pose a diagnostic and therapeutic challenge. Lymph node and lung involvement are common and may serve as distinguishing features. With over 5 years of follow up, all patients are alive with only a single patient who progressed. While numbers are small and patients were selected, these data indicate excellent long-term outcomes in patients with LPL-associated amyloidosis treated with risk adapted melphalan and suggest BEAM conditioning may not be essential.