title: Interphase fluorescence in situ hybridization in untreated AL amyloidosis has an independent prognostic impact by abnormality type and treatment category.
abstract: The significance of interphase fluorescence in situ hybridization (iFISH) by regimen type was assessed in 692 immunoglobulin light-chain (AL) amyloidosis patients with iFISH at diagnosis. First-line treatment was categorized as stem cell transplant and three non-transplant regimens. The most common abnormality was t(11;14) (49% of patients) followed by monosomy 13/del(13q) (36%) and trisomies (26%). A lower rate of very good partial response (VGPR) or better was observed in patients with t(11;14) treated with bortezomib-based (52% vs 77%; P=0.004) and IMiD-based regimens (13% vs 54%; P=0.04) compared with those lacking t(11;14). This corresponded to an inferior overall survival (OS) in t(11;14)-positive bortezomib-treated (median 15 vs 27 months; P=0.05) and IMiD-treated patients (median 12 vs 32 months; P=0.05). The inferior OS associated with t(11;14) bortezomib-treated patients was restricted to patients with favorable disease. Trisomies were associated with a shorter OS (median 29 vs 69 months; P=0.001), reaching statistical significance only for melphalan (median 15 vs 32 months; P=0.02). Multivariate analysis confirmed an independent survival impact for trisomies in the entire cohort and for t(11;14) among bortezomib-treated patients. iFISH is prognostic in untreated AL amyloidosis and may influence treatment selection. Patients with t(11;14) should be considered for ASCT or standard-dose melphalan at diagnosis because the survival disadvantage may be abrogated.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: E
authors.initials: E
authors.lastname: Muchtar
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Dispenzieri
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Kumar
authors.affiliation: Cytogenetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Ketterling
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: D
authors.initials: D
authors.lastname: Dingli
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: M Q
authors.initials: MQ
authors.lastname: Lacy
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: F K
authors.initials: FK
authors.lastname: Buadi
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Hayman
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kapoor
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.|Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
authors.forename: N
authors.identifier: 0000-0002-5651-1411
authors.initials: N
authors.lastname: Leung
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.|Hospitalist Services, Essentia Health St. Joseph's Hospital, Brainerd, MN, USA.
authors.forename: R
authors.initials: R
authors.lastname: Chakraborty
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: W
authors.initials: W
authors.lastname: Gonsalves
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: R
authors.initials: R
authors.lastname: Warsame
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: T V
authors.initials: TV
authors.lastname: Kourelis
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Russell
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Lust
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Go
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Zeldenrust
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Kyle
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Rajkumar
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Gertz
mesh_terms: D000368:Aged; D000686:Amyloidosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007399:Interphase; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014178:Translocation, Genetic; D014314:Trisomy