PMID- 23353119
OWN - NLM
STAT- MEDLINE
DCOM- 20130829
LR  - 20240413
IS  - 1523-6536 (Electronic)
IS  - 1083-8791 (Print)
IS  - 1083-8791 (Linking)
VI  - 19
IP  - 4
DP  - 2013 Apr
TI  - Partially mismatched transplantation and human leukocyte antigen donor-specific 
      antibodies.
PG  - 647-52
LID - S1083-8791(13)00052-9 [pii]
LID - 10.1016/j.bbmt.2013.01.016 [doi]
AB  - The presence of donor human leukocyte antigen (HLA)-specific antibodies (DSA) 
      increases engraftment failure risk in partially HLA-mismatched, or 
      HLA-haploidentical, allogeneic marrow (alloBMT) transplantation. As pre-existing 
      sensitization to HLA antigens is not well characterized among candidates for 
      HLA-haploidentical alloBMT, we retrospectively evaluated both the incidence and 
      relative strength of DSA in this patient population. Based on correlations of 
      solid-phase antibody assays on the Luminex (Luminex, Austin, TX) platform with 
      actual crossmatch tests, DSA were characterized as weak for results that were 
      consistent with negative flow cytometric crossmatch results or as 
      moderate-to-strong for results consistent with positive flow cytometric or 
      cytotoxicity crossmatches. We evaluated 296 alloBMT candidates; 111 (37.5%) were 
      female. DSA were detected in 43 (14.5%) candidates, mostly among female 
      candidates (42.9% female versus 12.5% male). Moderate-to-strong DSA strength was 
      more frequently encountered when directed against haploidentical donors as 
      compared with mismatched unrelated donors. DSA were most commonly detected in 
      female patients directed against their children. Because the presence of DSA has 
      been considered prohibitive for HLA-mismatched alloBMT, we additionally report a 
      desensitization methodology used to reduce DSA to negative or weak levels, ie, 
      levels well below those detectable in a flow cytometric crossmatch. Nine patients 
      without other available donors underwent desensitization. Eight who reduced their 
      DSA to negative or weak levels proceeded to alloBMT and achieved full donor 
      engraftment. These data support routine DSA evaluation in all patients considered 
      for mismatched alloBMT; however, for patients with no other viable options, 
      desensitization to weak or negative DSA levels may afford the opportunity for 
      successful transplantation.
CI  - Copyright (c) 2013 American Society for Blood and Marrow Transplantation. Published 
      by Elsevier Inc. All rights reserved.
FAU - Gladstone, Douglas E
AU  - Gladstone DE
AD  - Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, 
      MD 21287, USA. dgladst1@jhmi.edu
FAU - Zachary, Andrea A
AU  - Zachary AA
FAU - Fuchs, Ephraim J
AU  - Fuchs EJ
FAU - Luznik, Leo
AU  - Luznik L
FAU - Kasamon, Yvette L
AU  - Kasamon YL
FAU - King, Karen E
AU  - King KE
FAU - Brodsky, Robert A
AU  - Brodsky RA
FAU - Jones, Richard J
AU  - Jones RJ
FAU - Leffell, Mary S
AU  - Leffell MS
LA  - eng
GR  - P01 CA015396/CA/NCI NIH HHS/United States
GR  - P30 CA006973/CA/NCI NIH HHS/United States
GR  - P01 CA15396/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130122
PL  - United States
TA  - Biol Blood Marrow Transplant
JT  - Biology of blood and marrow transplantation : journal of the American Society for 
      Blood and Marrow Transplantation
JID - 9600628
RN  - 0 (HLA Antigens)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Isoantibodies)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Adult
MH  - Aged
MH  - *Bone Marrow Transplantation
MH  - Child
MH  - *Desensitization, Immunologic
MH  - Female
MH  - Graft vs Host Disease/blood/*immunology/mortality
MH  - HLA Antigens/*immunology
MH  - Haplotypes
MH  - Histocompatibility Testing
MH  - Humans
MH  - Immunoglobulins, Intravenous/therapeutic use
MH  - Isoantibodies/*blood/immunology
MH  - Male
MH  - Middle Aged
MH  - Retrospective Studies
MH  - Sex Factors
MH  - Tacrolimus/therapeutic use
MH  - Transplantation, Homologous
MH  - Unrelated Donors
PMC - PMC3768172
MID - NIHMS438442
COIS- Conflict of Interest Statement: There are no conflicts of interest to report.
EDAT- 2013/01/29 06:00
MHDA- 2013/08/30 06:00
PMCR- 2014/04/01
CRDT- 2013/01/29 06:00
PHST- 2012/11/06 00:00 [received]
PHST- 2013/01/17 00:00 [accepted]
PHST- 2013/01/29 06:00 [entrez]
PHST- 2013/01/29 06:00 [pubmed]
PHST- 2013/08/30 06:00 [medline]
PHST- 2014/04/01 00:00 [pmc-release]
AID - S1083-8791(13)00052-9 [pii]
AID - 10.1016/j.bbmt.2013.01.016 [doi]
PST - ppublish
SO  - Biol Blood Marrow Transplant. 2013 Apr;19(4):647-52. doi: 
      10.1016/j.bbmt.2013.01.016. Epub 2013 Jan 22.