Impact of genetic abnormalities on survival after allogeneic hematopoietic stem cell transplantation in multiple myeloma.
We analyzed the prognostic impact of the most frequent genetic abnormalities detected by fluorescence in situ hybridization in 101 patients with multiple myeloma, who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after melphalan/fludarabine-based reduced conditioning. The incidences of abnormalities in the present analysis were as follows: del(13q14) (61%), t(11;14)(q13;q32) (14%), t(4;14)(p16.3;q32) (19%), MYC-gain gains (8q24) (21%), del(17p13) (16%) and t(14;16)(q32;q23) (5%). None of the patients had t(6;14)(p25;q32). The overall complete remission (CR) rate was 50% with no differences between the genetic abnormalities except for patients with del(17p13) who achieved less CR (7 vs 56%; P=0.001). Univariate analysis revealed a higher relapse rate in patients aged >50 years (P=0.002), patients with del(13q14) (P=0.006) and patients with del(17p13) (P=0.003). In multivariate analyses, only del(13q14) (HR: 2.34, P=0.03) and del(17p13) (HR: 2.24; P=0.04) significantly influenced the incidence of relapse, whereas for event-free survival, only age (HR 2.8; P=0.01) and del(17p13) (HR: 2.05; P=0.03) retained their negative prognostic value. These data show that del(17p13) is a negative prognostic factor for achieving CR as well as for event-free survival after HSCT. Translocation t(4;14) might be overcome by allogeneic HSCT, which will have implication for risk-adapted strategies.
Schilling
G
G
Department of Oncology and Hematology, Medical Clinic II, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Hansen
T
T
Shimoni
A
A
Zabelina
T
T
Pérez-Simón
J-A
JA
Simon-Perez
J-A
JA
Gutierrez
N C
NC
Bethge
W
W
Liebisch
P
P
Schwerdtfeger
R
R
Bornhäuser
M
M
Otterstetter
S
S
Penas
E M M
EM
Dierlamm
J
J
Ayuk
F
F
Atanackovic
D
D
Bacher
U
U
Bokemeyer
C
C
Zander
A
A
San Miguel
J
J
Miguel
J S
JS
Nagler
A
A
Kröger
N
N
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan