title: Prognostic impact of cytogenetic aberrations in AL amyloidosis patients after high-dose melphalan: a long-term follow-up study.
abstract: Cytogenetic aberrations detected by interphase fluorescence in situ hybridization (iFISH) of plasma cells are routinely evaluated as prognostic markers in multiple myeloma. This long-term follow-up study aimed to assess the prognosis of systemic light chain amyloidosis (AL) patients treated with high-dose melphalan (HDM) chemotherapy and autologous stem cell transplantation, depending on iFISH results. Therefore, we analyzed a consecutive cohort of 123 AL patients recruited from 2003 to 2014. HDM was safe, with only 1 of 123 patients dying as a result of treatment-related mortality, and effective, with a complete remission (CR) rate of 34%. Translocation t(11;14) as the most prevalent aberration (59%) led to an improved CR rate after high-dose therapy (41.2% vs 20.0%; P = .02), translating into a prolonged hematologic event-free survival (hemEFS; median, 46.1 vs 28.1 months; P = .05) and a trend for better overall survival (median, not reached vs 93.7 months; P = .07). In multivariate analysis, t(11;14) was confirmed as a favorable prognostic factor regarding hemEFS along with lower values for the difference between involved and uninvolved free light chains. Conversely, deletion 13q14, gain of 1q21, and hyperdiploidy had no significant prognostic impact. The high-risk cytogenetic aberrations t(4;14), t(14;16), and del(17p13) conferred an unfavorable prognosis, although statistical significance was reached only for univariate CR analysis in this small group of 9 patients. Thus, t(11;14) positivity in HDM-treated AL patients conferred superior CR rates and hemEFS. In view of the reduced response of t(11;14) to bortezomib, this highlights the impact of therapy on the prognostic role of cytogenetic aberrations.
authors.affiliation: Amyloidosis Center, and Division of Hematology/Oncology/Rheumatology, Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany;
authors.forename: Tilmann
authors.initials: T
authors.lastname: Bochtler
authors.affiliation: Amyloidosis Center, and Division of Hematology/Oncology/Rheumatology, Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany;
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.affiliation: Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany;
authors.forename: Christina
authors.initials: C
authors.lastname: Kunz
authors.affiliation: Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany;
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.affiliation: Amyloidosis Center, and Division of Hematology/Oncology/Rheumatology, Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany;
authors.forename: Christoph
authors.initials: C
authors.lastname: Kimmich
authors.affiliation: Division of Hematology/Oncology/Rheumatology, Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany;
authors.forename: Anja
authors.initials: A
authors.lastname: Seckinger
authors.affiliation: Division of Hematology/Oncology/Rheumatology, Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany;
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.affiliation: Division of Hematology/Oncology/Rheumatology, Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany; National Center for Tumor Diseases, Heidelberg, Germany; and.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.affiliation: Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Granzow
authors.affiliation: Division of Hematology/Oncology/Rheumatology, Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany;
authors.forename: Peter
authors.initials: P
authors.lastname: Dreger
authors.affiliation: Amyloidosis Center, and Division of Hematology/Oncology/Rheumatology, Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany;
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Jauch
authors.affiliation: Amyloidosis Center, and Division of Hematology/Oncology/Rheumatology, Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany;
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Schönland
mesh_terms: D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000235:genetics / Q000401:mortality / Q000628:therapy; D064592:Autografts; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007147:Immunoglobulin Light Chains; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D012074:Remission Induction; D015996:Survival Rate
chemical_list: D007147:Immunoglobulin Light Chains; D008558:Melphalan