title: Translocation t(11;14) is associated with adverse outcome in patients with newly diagnosed AL amyloidosis when treated with bortezomib-based regimens.
abstract: OBJECTIVE
  Bortezomib has become a cornerstone in the treatment of AL amyloidosis. In this study, we addressed the prognostic impact of cytogenetic aberrations for bortezomib-treated patients.
  
  
  METHODS
  We analyzed a consecutive series of 101 patients with AL amyloidosis treated with bortezomib-dexamethasone as first-line treatment by interphase fluorescence in situ hybridization (iFISH). Patients were ineligible for high-dose chemotherapy, which would put them at risk for cardiac or renal failure, and thus represented a poor-risk group.
  
  
  RESULTS
  Presence of t(11;14), versus its absence, was associated with inferior hematologic event-free survival (median, 3.4 v 8.8 months, respectively; P = .002), overall survival (median, 8.7 v 40.7 months, respectively; P = .05), and remission rate (≥ very good partial remission; 23% v 47%, respectively; P = .02). In multivariable Cox regression models incorporating established hematologic and clinical risk factors, t(11;14) was an independent adverse prognostic marker for hematologic event-free survival (hazard ratio, 2.94; 95% CI, 1.37 to 6.25; P = .006) and overall survival (hazard ratio, 3.13; 95% CI, 1.16 to 8.33; P = .03), but not for remission (≥ very good partial remission). Markedly, the multiple myeloma high-risk iFISH aberrations t(4;14), t(14;16), del(17p), and gain of 1q21 conferred no adverse prognosis in this bortezomib-dexamethasone-treated group. After backward variable selection, the final multivariable model was validated in a consecutive series of 32 patients treated with bortezomib, dexamethasone, and cyclophosphamide.
  
  
  CONCLUSIONS
  iFISH results are important independent prognostic factors in AL amyloidosis. In contrast to our recently published results with melphalan and dexamethasone standard therapy, bortezomib is less beneficial to patients harboring t(11;14), whereas it effectively alleviates the poor prognosis inherent to high-risk aberrations. Given the discrepant response to different treatment modalities, iFISH may help to guide therapeutic choices in these poor-risk patients requiring rapid hematologic response.
authors.affiliation: Tilmann Bochtler, Ute Hegenbart, Anja Seckinger, Christoph Kimmich, Hartmut Goldschmidt, Anthony D. Ho, Dirk Hose, and Stefan O. Schönland, Amyloidosis Center, University Hospital Heidelberg; Christina Kunz and Axel Benner, German Cancer Research Center; Martin Granzow and Anna Jauch, Institute of Human Genetics, University Heidelberg; and Hartmut Goldschmidt and Dirk Hose, National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Tilmann
authors.initials: T
authors.lastname: Bochtler
authors.affiliation: Tilmann Bochtler, Ute Hegenbart, Anja Seckinger, Christoph Kimmich, Hartmut Goldschmidt, Anthony D. Ho, Dirk Hose, and Stefan O. Schönland, Amyloidosis Center, University Hospital Heidelberg; Christina Kunz and Axel Benner, German Cancer Research Center; Martin Granzow and Anna Jauch, Institute of Human Genetics, University Heidelberg; and Hartmut Goldschmidt and Dirk Hose, National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.affiliation: Tilmann Bochtler, Ute Hegenbart, Anja Seckinger, Christoph Kimmich, Hartmut Goldschmidt, Anthony D. Ho, Dirk Hose, and Stefan O. Schönland, Amyloidosis Center, University Hospital Heidelberg; Christina Kunz and Axel Benner, German Cancer Research Center; Martin Granzow and Anna Jauch, Institute of Human Genetics, University Heidelberg; and Hartmut Goldschmidt and Dirk Hose, National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Kunz
authors.affiliation: Tilmann Bochtler, Ute Hegenbart, Anja Seckinger, Christoph Kimmich, Hartmut Goldschmidt, Anthony D. Ho, Dirk Hose, and Stefan O. Schönland, Amyloidosis Center, University Hospital Heidelberg; Christina Kunz and Axel Benner, German Cancer Research Center; Martin Granzow and Anna Jauch, Institute of Human Genetics, University Heidelberg; and Hartmut Goldschmidt and Dirk Hose, National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Granzow
authors.affiliation: Tilmann Bochtler, Ute Hegenbart, Anja Seckinger, Christoph Kimmich, Hartmut Goldschmidt, Anthony D. Ho, Dirk Hose, and Stefan O. Schönland, Amyloidosis Center, University Hospital Heidelberg; Christina Kunz and Axel Benner, German Cancer Research Center; Martin Granzow and Anna Jauch, Institute of Human Genetics, University Heidelberg; and Hartmut Goldschmidt and Dirk Hose, National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.affiliation: Tilmann Bochtler, Ute Hegenbart, Anja Seckinger, Christoph Kimmich, Hartmut Goldschmidt, Anthony D. Ho, Dirk Hose, and Stefan O. Schönland, Amyloidosis Center, University Hospital Heidelberg; Christina Kunz and Axel Benner, German Cancer Research Center; Martin Granzow and Anna Jauch, Institute of Human Genetics, University Heidelberg; and Hartmut Goldschmidt and Dirk Hose, National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Seckinger
authors.affiliation: Tilmann Bochtler, Ute Hegenbart, Anja Seckinger, Christoph Kimmich, Hartmut Goldschmidt, Anthony D. Ho, Dirk Hose, and Stefan O. Schönland, Amyloidosis Center, University Hospital Heidelberg; Christina Kunz and Axel Benner, German Cancer Research Center; Martin Granzow and Anna Jauch, Institute of Human Genetics, University Heidelberg; and Hartmut Goldschmidt and Dirk Hose, National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kimmich
authors.affiliation: Tilmann Bochtler, Ute Hegenbart, Anja Seckinger, Christoph Kimmich, Hartmut Goldschmidt, Anthony D. Ho, Dirk Hose, and Stefan O. Schönland, Amyloidosis Center, University Hospital Heidelberg; Christina Kunz and Axel Benner, German Cancer Research Center; Martin Granzow and Anna Jauch, Institute of Human Genetics, University Heidelberg; and Hartmut Goldschmidt and Dirk Hose, National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.affiliation: Tilmann Bochtler, Ute Hegenbart, Anja Seckinger, Christoph Kimmich, Hartmut Goldschmidt, Anthony D. Ho, Dirk Hose, and Stefan O. Schönland, Amyloidosis Center, University Hospital Heidelberg; Christina Kunz and Axel Benner, German Cancer Research Center; Martin Granzow and Anna Jauch, Institute of Human Genetics, University Heidelberg; and Hartmut Goldschmidt and Dirk Hose, National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Tilmann Bochtler, Ute Hegenbart, Anja Seckinger, Christoph Kimmich, Hartmut Goldschmidt, Anthony D. Ho, Dirk Hose, and Stefan O. Schönland, Amyloidosis Center, University Hospital Heidelberg; Christina Kunz and Axel Benner, German Cancer Research Center; Martin Granzow and Anna Jauch, Institute of Human Genetics, University Heidelberg; and Hartmut Goldschmidt and Dirk Hose, National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.affiliation: Tilmann Bochtler, Ute Hegenbart, Anja Seckinger, Christoph Kimmich, Hartmut Goldschmidt, Anthony D. Ho, Dirk Hose, and Stefan O. Schönland, Amyloidosis Center, University Hospital Heidelberg; Christina Kunz and Axel Benner, German Cancer Research Center; Martin Granzow and Anna Jauch, Institute of Human Genetics, University Heidelberg; and Hartmut Goldschmidt and Dirk Hose, National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Jauch
authors.affiliation: Tilmann Bochtler, Ute Hegenbart, Anja Seckinger, Christoph Kimmich, Hartmut Goldschmidt, Anthony D. Ho, Dirk Hose, and Stefan O. Schönland, Amyloidosis Center, University Hospital Heidelberg; Christina Kunz and Axel Benner, German Cancer Research Center; Martin Granzow and Anna Jauch, Institute of Human Genetics, University Heidelberg; and Hartmut Goldschmidt and Dirk Hose, National Center for Tumor Diseases, Heidelberg, Germany. Stefan.Schoenland@med.uni-heidelberg.de.
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Schönland
mesh_terms: D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D003520:Cyclophosphamide / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000276:immunology; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011719:Pyrazines / Q000627:therapeutic use*; D012189:Retrospective Studies; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D007147:Immunoglobulin Light Chains; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone; D003520:Cyclophosphamide