Treatment-Related Mortality in Patients with AL Amyloidosis Undergoing High-Dose Melphalan and Stem Cell Transplantation: Trend Over the Past 14 Years at a Single Institution
Authors: Sanchorawala Vaishali , Skinner Martha , Finn Kathleen T. , Quillen Karen , Seldin David C. 
Published: April 2020

AL amyloidosis is caused by a clonal plasma cell dyscrasia and characterized by widespread, progressive amyloid deposition leading to multisystem organ failure and death. Aggressive treatment of AL amyloidosis with high dose intravenous melphalan followed by autologous stem cell transplantation (HDM/SCT) is effective in inducing hematologic and clinical remissions and in extending survival. However, HDM/SCT is a challenging treatment for patients with AL amyloidosis, given their multisystem disease. Morbidity and mortality are associated with all phases of HDM/SCT: during stem cell mobilization and collection, during post-treatment myelosuppression, and following hematopoietic engraftment. Between 7/1994 and 7/2008, 496 HDM/SCT were performed for patients with AL amyloidosis, (median age = 56, range 28–80), at Boston University Medical Center. Treatment-related mortality is defined as deaths during stem cell mobilization and collection phase as well as within 100 days after SCT. Overall treatment-related mortality was 12% (58/496). Of the 58 deaths, 11 (2%) occurred during the stem cell mobilization and collection phase of treatment, while 47 (9%) occurred within 100 days after SCT. Deaths during stem cell mobilization and collection were associated with cardiac arrhythmia (n=1), irreversible congestive heart failure (n=2), refractory hypotension (n=3), myocardial infarction due to small vessel amyloid disease (n=1), massive GI bleeding (n=3) and pulmonary embolism (n=1). There were 5 cardiac arrests leading to death during the stem cell infusion procedure. There were additional 42 deaths from D + 1 to D + 100 after SCT. Deaths during this period were associated with sepsis (33%), cardiac arrhythmia (26%) and hemorrhagic complications (10%). Overall treatment-related mortality was 14% (52/371) during the period from 7/1994 to 7/2004, the first decade of HDM/SCT for patients with AL amyloidosis at Boston University Medical Center. However, overall treatment-related mortality has considerably improved to 5% (6/125) during the period from 8/2004 to 7/2008. Improvement in treatment-related mortality rate over the past 14 years at this institution may be due to improved patient selection, to improvement in supportive care and to the cumulative experience of the treating multidisciplinary team physicians. In summary, HDM/SCT in AL amyloidosis presents unique clinical challenges, particularly because of the cardiovascular instability of patients and the risks of both thrombosis and bleeding. Both clinicians and patients who proceed with this aggressive form of therapy must be prepared for both the usual and unusual toxicities that may occur. Treatment-related mortality can be expected to be substantially greater at centers with limited experience with HDM/SCT for AL amyloidosis, compared with centers with much experience that focus on this complex disease.