title: Primary amyloidosis patients with significant organ dysfunction tolerate autologous transplantation after conditioning with single-dose total body irradiation alone: a feasibility study.
abstract: High-dose melphalan has been commonly used as conditioning for amyloidosis with considerable toxicity. We hypothesized that the novel conditioning regimen of 550 cGy total body irradiation (TBI) alone for autologous peripheral blood stem cell transplantation would have reduced organ toxicity and thus permit safer transplantation of primary amyloidosis patients, even those with poor risk disease. The comprehensive regimen included pretransplantation chemotherapy, single-dose TBI alone (550 cGy at 30 cGy/min) conditioning, and post-transplantation interferon-alpha maintenance. Thirteen patients were enrolled in this feasibility study. Patients with multiorgan involvement were included; 10 patients had poor or intermediate risk disease. Cardiac toxicity was significant. Treatment-related mortality through 100 days post-transplantation was 15% and was caused by cardiac mortality. One patient died from arrhythmia after receiving TBI; 2 patients had grade IV cardiac toxicity (with subsequent complete recovery). One patient died 1 month after mobilization from progressive cardiomyopathy and never received conditioning. However, noncardiac organ toxicity was mild. No patient required parenteral nutrition support; no patient developed mucositis; and no patient experienced gastrointestinal bleeding following transplantation. The complete hematologic remission rate was 45%, with pretransplantation chemotherapy being the most active part of the regimen. Survival estimates from enrollment to 1 and 2 years post-transplantation were 66% and 47%, respectively. Causes of death were disease progression (6), myelodysplasia (1), arrhythmia following TBI (1), and congestive heart failure after mobilization (1). In this cohort of primary amyloidosis patients, the transplantation regimen of 550 cGy TBI was feasible and associated with modest treatment-related mortality. Efficacy with TBI conditioning may be reduced compared with high-dose melphalan, but this should be explored in a future trial with a larger cohort of patients.
authors.affiliation: Division of Oncology, Section of Bone Marrow Transplantation and Leukemia, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110-1093, USA. wblum@im.wustl.edu
authors.forename: William
authors.initials: W
authors.lastname: Blum
authors.forename: Hanna
authors.initials: H
authors.lastname: Khoury
authors.forename: H-S
authors.initials: HS
authors.lastname: Lin
authors.forename: Ravi
authors.initials: R
authors.lastname: Vij
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Goodnough
authors.forename: Steve
authors.initials: S
authors.lastname: Devine
authors.forename: John
authors.initials: J
authors.lastname: Dipersio
authors.forename: Douglas
authors.initials: D
authors.lastname: Adkins
mesh_terms: D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000209:etiology; D002423:Cause of Death; D015331:Cohort Studies; D003131:Combined Modality Therapy; D018450:Disease Progression; D005240:Feasibility Studies; D005260:Female; D006321:Heart / Q000528:radiation effects; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009436:Neural Tube Defects / Q000209:etiology; D036102:Peripheral Blood Stem Cell Transplantation; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology / Q000401:mortality; D012074:Remission Induction; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000009:adverse effects