PMID- 25371177
OWN - NLM
STAT- MEDLINE
DCOM- 20150803
LR  - 20210103
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 29
IP  - 5
DP  - 2015 May
TI  - Incidence, risk factors and clinical outcome of leukemia relapses with loss of 
      the mismatched HLA after partially incompatible hematopoietic stem cell 
      transplantation.
PG  - 1143-52
LID - 10.1038/leu.2014.314 [doi]
AB  - Genomic loss of the mismatched human leukocyte antigen (HLA) is a recently 
      described mechanism of leukemia immune escape and relapse after allogeneic 
      hematopoietic stem cell transplantation (HSCT). Here we first evaluated its 
      incidence, risk factors and outcome in 233 consecutive transplants from partially 
      HLA-mismatched related and unrelated donors (MMRD and MMUD, respectively). We 
      documented 84 relapses, 23 of which with HLA loss. All the HLA loss relapses 
      occurred after MMRD HSCT, and 20/23 in patients with acute myeloid leukemia. Upon 
      MMRD HSCT, HLA loss variants accounted for 33% of the relapses (23/69), occurring 
      later than their 'classical' counterparts (median: 307 vs 88 days, P<0.0001). 
      Active disease at HSCT increased the risk of HLA loss (hazard ratio (HR): 10.16; 
      confidence interval (CI): 2.65-38.92; P=0.001), whereas older patient ages had a 
      protective role (HR: 0.16; CI: 0.05-0.46; P=0.001). A weaker association with HLA 
      loss was observed for graft T-cell dose and occurrence of chronic 
      graft-versus-host disease. Outcome after 'classical' and HLA loss relapses was 
      similarly poor, and second transplantation from a different donor appeared to 
      provide a slight advantage for survival. In conclusion, HLA loss is a frequent 
      mechanism of evasion from T-cell alloreactivity and relapse in patients with 
      myeloid malignancies transplanted from MMRDs, warranting routine screening in 
      this transplantation setting.
FAU - Crucitti, L
AU  - Crucitti L
AD  - Hematology and Bone Marrow Transplantation Unit, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy.
FAU - Crocchiolo, R
AU  - Crocchiolo R
AD  - Humanitas Cancer Center, Rozzano, Italy.
FAU - Toffalori, C
AU  - Toffalori C
AD  - Unit of Molecular and Functional Immunogenetics, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy.
FAU - Mazzi, B
AU  - Mazzi B
AD  - Unit of Molecular and Functional Immunogenetics, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy.
FAU - Greco, R
AU  - Greco R
AD  - Hematology and Bone Marrow Transplantation Unit, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy.
FAU - Signori, A
AU  - Signori A
AD  - Department of Health Sciences, Section of Biostatistics, University of Genova, 
      Genova, Italy.
FAU - Sizzano, F
AU  - Sizzano F
AD  - San Raffaele Flow Cytometry Resource, Analytical Cytology Technical Applications 
      Laboratory, IRCCS San Raffaele Scientific Institute, Milano, Italy.
FAU - Chiesa, L
AU  - Chiesa L
AD  - Unit of Molecular and Functional Immunogenetics, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy.
FAU - Zino, E
AU  - Zino E
AD  - Unit of Molecular and Functional Immunogenetics, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy.
FAU - Lupo Stanghellini, M T
AU  - Lupo Stanghellini MT
AD  - Hematology and Bone Marrow Transplantation Unit, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy.
FAU - Assanelli, A
AU  - Assanelli A
AD  - Hematology and Bone Marrow Transplantation Unit, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy.
FAU - Carrabba, M G
AU  - Carrabba MG
AD  - Hematology and Bone Marrow Transplantation Unit, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy.
FAU - Marktel, S
AU  - Marktel S
AD  - Hematology and Bone Marrow Transplantation Unit, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy.
FAU - Marcatti, M
AU  - Marcatti M
AD  - Hematology and Bone Marrow Transplantation Unit, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy.
FAU - Bordignon, C
AU  - Bordignon C
AD  - 1] Universita 'Vita-Salute San Raffaele', Milano, Italy [2] MolMed SpA, Milano, 
      Italy.
FAU - Corti, C
AU  - Corti C
AD  - Hematology and Bone Marrow Transplantation Unit, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy.
FAU - Bernardi, M
AU  - Bernardi M
AD  - Hematology and Bone Marrow Transplantation Unit, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy.
FAU - Peccatori, J
AU  - Peccatori J
AD  - Hematology and Bone Marrow Transplantation Unit, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy.
FAU - Bonini, C
AU  - Bonini C
AD  - Experimental Hematology Unit, Division of Immunology, Transplantation and 
      Infectious Disease, IRCCS San Raffaele Scientific Institute, Milano, Italy.
FAU - Fleischhauer, K
AU  - Fleischhauer K
AD  - 1] Unit of Molecular and Functional Immunogenetics, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy [2] Institute for Experimental Cellular Therapy, University of 
      Essen, Essen, Germany.
FAU - Ciceri, F
AU  - Ciceri F
AD  - Hematology and Bone Marrow Transplantation Unit, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy.
FAU - Vago, L
AU  - Vago L
AD  - 1] Hematology and Bone Marrow Transplantation Unit, Division of Regenerative 
      Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, 
      Milano, Italy [2] Unit of Molecular and Functional Immunogenetics, Division of 
      Regenerative Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific 
      Institute, Milano, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141105
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Female
MH  - Graft vs Host Disease/immunology
MH  - HLA Antigens/*immunology
MH  - Hematopoietic Stem Cell Transplantation/*methods
MH  - Histocompatibility Testing
MH  - Humans
MH  - Incidence
MH  - Leukemia, Myeloid, Acute/epidemiology/*immunology/*therapy
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Proportional Hazards Models
MH  - Recurrence
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Young Adult
EDAT- 2014/11/06 06:00
MHDA- 2015/08/04 06:00
CRDT- 2014/11/06 06:00
PHST- 2014/07/16 00:00 [received]
PHST- 2014/10/06 00:00 [revised]
PHST- 2014/10/23 00:00 [accepted]
PHST- 2014/11/06 06:00 [entrez]
PHST- 2014/11/06 06:00 [pubmed]
PHST- 2015/08/04 06:00 [medline]
AID - leu2014314 [pii]
AID - 10.1038/leu.2014.314 [doi]
PST - ppublish
SO  - Leukemia. 2015 May;29(5):1143-52. doi: 10.1038/leu.2014.314. Epub 2014 Nov 5.