PMID- 18997170
OWN - NLM
STAT- MEDLINE
DCOM- 20090428
LR  - 20210206
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 113
IP  - 12
DP  - 2009 Mar 19
TI  - HLA mismatch combinations associated with decreased risk of relapse: implications 
      for the molecular mechanism.
PG  - 2851-8
LID - 10.1182/blood-2008-08-171934 [doi]
AB  - The finding that the risk of relapse in hematologic malignancy decreases after 
      allogeneic hematopoietic stem cell transplantation (HSCT) has lead to the concept 
      of a graft-versus-leukemia (GVL) effect. However, this beneficial effect is 
      considered to be frequently offset by graft-versus-host disease (GVHD). Thus, 
      improving HSCT outcomes by separating GVL from GVHD is a key clinical issue. This 
      cohort study registered 4643 patients with hematologic malignancies who received 
      transplants from unrelated donors. Six major human leukocyte antigen (HLA) loci 
      were retrospectively genotyped. We identified 4 HLA-Cw and 6 HLA-DPB1 mismatch 
      combinations responsible for a decreased risk of relapse; of these, 8 of 10 
      combinations were different from those responsible for severe acute GVHD, 
      including all 6 of the HLA-DPB1 combinations. Pairs with these combinations of 
      HLA-DPB1 were associated with a significantly better overall survival than were 
      completely matched pairs. Moreover, several amino acid substitutions on specific 
      positions responsible for a decreased risk of relapse were identified in HLA-Cw, 
      but not in HLA-DPB1. These findings might be crucial to elucidating the mechanism 
      of the decreased risk of relapse on the basis of HLA molecule. Donor selection 
      made in consideration of these results might allow the separation of GVL from 
      acute GVHD, especially in HLA-DPB1 mismatch combinations.
FAU - Kawase, Takakazu
AU  - Kawase T
AD  - Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan.
FAU - Matsuo, Keitaro
AU  - Matsuo K
FAU - Kashiwase, Koichi
AU  - Kashiwase K
FAU - Inoko, Hidetoshi
AU  - Inoko H
FAU - Saji, Hiroh
AU  - Saji H
FAU - Ogawa, Seishi
AU  - Ogawa S
FAU - Kato, Shunichi
AU  - Kato S
FAU - Sasazuki, Takehiko
AU  - Sasazuki T
FAU - Kodera, Yoshihisa
AU  - Kodera Y
FAU - Morishima, Yasuo
AU  - Morishima Y
CN  - Japan Marrow Donor Program
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081107
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (HLA-C Antigens)
RN  - 0 (HLA-DP Antigens)
RN  - 0 (HLA-DP beta-Chains)
RN  - 0 (HLA-DPB1 antigen)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Amino Acid Substitution
MH  - Cohort Studies
MH  - Disease-Free Survival
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Graft vs Host Disease/epidemiology/immunology
MH  - Graft vs Leukemia Effect/immunology
MH  - HLA-C Antigens/chemistry/genetics/*immunology
MH  - HLA-DP Antigens/chemistry/genetics/*immunology
MH  - HLA-DP beta-Chains
MH  - *Hematopoietic Stem Cell Transplantation
MH  - *Histocompatibility
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Leukemia/immunology/mortality/*surgery
MH  - Male
MH  - Multiple Myeloma/immunology/mortality/surgery
MH  - Proportional Hazards Models
MH  - Recurrence
MH  - Retrospective Studies
MH  - Risk
MH  - Transplantation, Homologous/immunology
MH  - Young Adult
EDAT- 2008/11/11 09:00
MHDA- 2009/04/29 09:00
CRDT- 2008/11/11 09:00
PHST- 2008/11/11 09:00 [pubmed]
PHST- 2009/04/29 09:00 [medline]
PHST- 2008/11/11 09:00 [entrez]
AID - S0006-4971(20)37552-2 [pii]
AID - 10.1182/blood-2008-08-171934 [doi]
PST - ppublish
SO  - Blood. 2009 Mar 19;113(12):2851-8. doi: 10.1182/blood-2008-08-171934. Epub 2008 
      Nov 7.