PMID- 36385618
OWN - NLM
STAT- MEDLINE
DCOM- 20230222
LR  - 20230314
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Linking)
VI  - 200
IP  - 5
DP  - 2023 Mar
TI  - Human leukocyte antigen evolutionary divergence influences outcomes of paediatric 
      patients and young adults affected by malignant disorders given allogeneic 
      haematopoietic stem cell transplantation from unrelated donors.
PG  - 622-632
LID - 10.1111/bjh.18561 [doi]
AB  - High genetic heterogeneity in the human leukocyte antigen (HLA) increases the 
      likelihood of efficient immune response to pathogens and tumours. As measure of 
      HLA diversity, HLA evolutionary divergence (HED) has been shown to predict the 
      response of tumours to immunotherapy and haematopoietic stem cell transplantation 
      (HSCT) in adults. We retrospectively investigated the association of HED with 
      outcomes of 153 paediatric/young adults patients, treated for malignant disorders 
      with HSCT from 9-10/10 HLA-matched unrelated donors. HED was calculated as 
      pairwise genetic distance between alleles in patient HLA-A, -B, -C, -DRB1, -DQB1 
      and -DPB1, using the locus median to stratify patients with 'high' or 'low' HED. 
      Patients with high HED-B and -DRB1 showed significantly improved disease-free 
      survival (DFS), especially when combined (70.8% vs 53.7% p = 0.008). High 
      HED-B + -DRB1 was also associated with improved overall survival (OS) (82.1 vs 
      66.4% p = 0.014), and concomitant reduction of non-relapse-mortality (5.1% vs 
      21.1% p = 0.006). The impact on OS and DFS of combined HED-B + -DRB1 was 
      confirmed in multivariate analysis [hazard ratio (HR) 0.39, p = 0.009; and HR 
      0.45, p = 0.007 respectively]. Only high HED scores for HLA-DPB1 were associated, 
      in univariate analysis, with reduced incidence of relapse (15.9% vs 31.1%, 
      p = 0.03). These results support HED as prognostic marker in allogeneic HSCT and, 
      if confirmed in larger cohorts, would allow its use to inform clinical risk and 
      potentially influence clinical practice.
CI  - (c) 2022 The Authors. British Journal of Haematology published by British Society 
      for Haematology and John Wiley & Sons Ltd.
FAU - Merli, Pietro
AU  - Merli P
AUID- ORCID: 0000-0001-6426-4046
AD  - Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesu 
      Children's Hospital, Rome, Italy.
FAU - Crivello, Pietro
AU  - Crivello P
AUID- ORCID: 0000-0001-9668-5013
AD  - Institute for Experimental Cellular Therapy, University Hospital Essen, Essen, 
      Germany.
FAU - Strocchio, Luisa
AU  - Strocchio L
AUID- ORCID: 0000-0002-5993-0857
AD  - Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesu 
      Children's Hospital, Rome, Italy.
FAU - Pinto, Rita Maria
AU  - Pinto RM
AD  - Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesu 
      Children's Hospital, Rome, Italy.
FAU - Algeri, Mattia
AU  - Algeri M
AD  - Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesu 
      Children's Hospital, Rome, Italy.
FAU - Del Bufalo, Francesca
AU  - Del Bufalo F
AD  - Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesu 
      Children's Hospital, Rome, Italy.
FAU - Pagliara, Daria
AU  - Pagliara D
AD  - Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesu 
      Children's Hospital, Rome, Italy.
FAU - Becilli, Marco
AU  - Becilli M
AD  - Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesu 
      Children's Hospital, Rome, Italy.
FAU - Carta, Roberto
AU  - Carta R
AD  - Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesu 
      Children's Hospital, Rome, Italy.
FAU - Gaspari, Stefania
AU  - Gaspari S
AUID- ORCID: 0000-0002-1387-0836
AD  - Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesu 
      Children's Hospital, Rome, Italy.
FAU - Galaverna, Federica
AU  - Galaverna F
AD  - Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesu 
      Children's Hospital, Rome, Italy.
FAU - Quagliarella, Francesco
AU  - Quagliarella F
AD  - Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesu 
      Children's Hospital, Rome, Italy.
FAU - Boz, Giulia
AU  - Boz G
AD  - Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesu 
      Children's Hospital, Rome, Italy.
FAU - Catanoso, Maria Luigia
AU  - Catanoso ML
AD  - Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesu 
      Children's Hospital, Rome, Italy.
FAU - Boccieri, Emilia
AU  - Boccieri E
AD  - Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesu 
      Children's Hospital, Rome, Italy.
FAU - Troiano, Maria
AU  - Troiano M
AD  - Laboratory of Transplant Immunogenetics, Department of Hematology/Oncology, Cell 
      and Gene Therapy, IRCCS Bambino Gesu Children's Hospital, Rome, Italy.
FAU - Fleischhauer, Katharina
AU  - Fleischhauer K
AUID- ORCID: 0000-0002-5827-8000
AD  - Institute for Experimental Cellular Therapy, University Hospital Essen, Essen, 
      Germany.
AD  - German Cancer Consortium, Partner Site Essen/Dusseldorf, Heidelberg, Germany.
FAU - Andreani, Marco
AU  - Andreani M
AUID- ORCID: 0000-0003-3451-3624
AD  - Laboratory of Transplant Immunogenetics, Department of Hematology/Oncology, Cell 
      and Gene Therapy, IRCCS Bambino Gesu Children's Hospital, Rome, Italy.
FAU - Locatelli, Franco
AU  - Locatelli F
AUID- ORCID: 0000-0002-7976-3654
AD  - Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesu 
      Children's Hospital, Rome, Italy.
AD  - Catholic University of the Sacred Heart, Department of Life Sciences and Public 
      Health, Rome, Italy.
LA  - eng
GR  - DFG FL 843/1-1/Deutsche Forschungsgemeinschaft/
GR  - DKMS-SLS-MHG-2018-01/Deutsche Knochermarkspenderdatei/
GR  - Joseph-Senker Stiftung/
GR  - GR-2011-02350175/Ministero della Salute/
GR  - DJCLS 11 R/2021/Deutsche Jose Carreras Leukamie Stiftung/
GR  - DJCLS 20R/2019/Deutsche Jose Carreras Leukamie Stiftung/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221116
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
SB  - IM
MH  - Humans
MH  - Child
MH  - Young Adult
MH  - Unrelated Donors
MH  - Retrospective Studies
MH  - Histocompatibility Testing
MH  - *Hematopoietic Stem Cell Transplantation/adverse effects
MH  - *Neoplasms/etiology
MH  - *Graft vs Host Disease
OTO - NOTNLM
OT  - haematopoietic stem cell transplantationhuman leukocyte antigen (HLA)HLA 
      evolutionary divergenceleukaemiapaediatric
EDAT- 2022/11/18 06:00
MHDA- 2023/02/22 06:00
CRDT- 2022/11/17 11:21
PHST- 2022/10/29 00:00 [revised]
PHST- 2022/07/07 00:00 [received]
PHST- 2022/10/31 00:00 [accepted]
PHST- 2022/11/18 06:00 [pubmed]
PHST- 2023/02/22 06:00 [medline]
PHST- 2022/11/17 11:21 [entrez]
AID - 10.1111/bjh.18561 [doi]
PST - ppublish
SO  - Br J Haematol. 2023 Mar;200(5):622-632. doi: 10.1111/bjh.18561. Epub 2022 Nov 16.