학술논문

Impact of Induction Therapy on the Outcome of Immunoglobulin Light Chain Amyloidosis after Autologous Hematopoietic Stem Cell Transplantation.
Document Type
Article
Source
Biology of Blood & Marrow Transplantation. Nov2018, Vol. 24 Issue 11, p2197-2203. 7p.
Subject
*AMYLOIDOSIS
*HEMATOPOIETIC stem cell transplantation
*MELPHALAN
*CANCER chemotherapy
*PROGRESSION-free survival
Language
ISSN
1083-8791
Abstract
Highlights • Achieving a hematologic CR was associated with a higher organ response rate and longer OS. • A low β 2 -microglobulin (<3.5) at diagnosis and the use of IMiD/PI as induction therapy emerged as independent predictors of longer OS. • Induction therapy with alkylating agents as well as novel agents (IMiD or PI) followed by high-dose melphalan and auto-HCT was feasible, safe, and effective; our study reports a lower incidence of 100-day and 1-year NRM (3% and 3%, respectively). • There was significantly higher HR after IMiD/PI induction compared with others (either conventional chemotherapy or no induction). Abstract With the availability of immunomodulatory imide drugs (IMiDs) and proteasome inhibitors (PI), most patients with immunoglobulin light chain amyloidosis (AL) receive induction therapy before autologous hematopoietic stem cell transplantation (auto-HCT). In this study we evaluated the type of induction therapy and its impact on the outcome of auto-HCT in AL. We identified 128 patients with AL who underwent high-dose chemotherapy and auto-HCT at our institution between 1997 and 2013. Patients were divided into 3 groups: no induction, conventional chemotherapy (CC)-based induction (melphalan, steroids), and IMiD/PI-based induction (thalidomide, lenalidomide, or bortezomib). The hematologic response (HR) and organ response were defined according to the established criteria. Median age at auto-HCT was 58 years (range, 35 to 75). Twenty patients (15.5%) received no induction, 25 (19.5%) received CC, and 83 (65%) received IMiDs/PIs. One, 2, or 3 or more organs were involved in 90 (70%), 20 (16%), and 18 (14%) patients, respectively. After auto-HCT 12 of 20 (60%), 15 of 24 (62%), and 72 of 83 (87%) assessable patients achieved HR at 100 days in no induction, CC, and IMiD/PI groups, respectively (P =.001). Organ response at 1 year after auto-HCT was seen in 7 of 18 (39%), 14 of 24 (58%), and 37 of 79 (47%) assessable patients in no induction, CC, and IMiD/PI groups, respectively (P =.3). Achieving a hematologic complete response was associated with a significantly higher probability of achieving an organ response (P =.02). After a median follow-up of 26 months, rates of 2-year progression-free survival were 67%, 56%, and 73% in no induction, CC, and IMiD/PI groups, respectively (P =.07; hazard ratio,.5; 95% confidence interval [CI],.3 to 1.1). Rates of 2-year overall survival were 73%, 76%, and 87% in no induction, CC, and IMiD/PI groups, respectively (P =.05; hazard ratio,.4; 95% CI,.2 to.9). On multivariate analysis a low β 2 -microglobulin (P =.01; hazard ratio,.3; 95% CI,.1 to.7) and induction therapy with IMiD/PI (P =.01; hazard ratio,.3; 95% CI,.1 to.7) were associated with a better overall survival. Induction therapy with either CC or IMiDs/PIs is safe and feasible in selected patients with AL. IMiD/PI-based induction is associated with a longer overall survival compared with patients who received no induction or CC before auto-HCT. [ABSTRACT FROM AUTHOR]