The Role of HLA Matching and Recipient Sensitization in Organ Allograft Outcome

Author(s):  
Brian Tait
Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 522-528 ◽  
Author(s):  
J McCullough ◽  
M Clay ◽  
D Hurd ◽  
K Richards ◽  
C Ludvigsen ◽  
...  

The effect of leukocyte antibodies detected under different conditions on the fate in vivo of granulocytes was studied using 111-indium- labeled granulocytes. Sera from patients were tested by granulocyte agglutination (GA), granulocytotoxicity (GC), granulocyte immunofluorescence (GIF), lymphocytotoxicity (LC), and antibody- dependent lymphocyte-mediated granulocytotoxicity. Granulocytes from donors to be studied were labeled with 111-indium and injected. Then the intravascular recovery and survival or tissue localization was determined in 93 studies. Antibodies detected by granulocyte agglutination were associated with a significant reduction in recovery (6.7% v 30.8% in controls; P less than .001) and t1/2 (0.3 hours v 5.6 hours in controls; P = .002). When all possible combinations of serum reactivity were considered, reactivity in the GA plus GIF assays had the best correlation with decreased recovery (R2 = .49; P less than .001) and t1/2 (R2 = .73; P less than .001). When the relationship between the strength of antibody reactivity and the recovery and t1/2 were analyzed, the best relationship was between the combination of LC and GIF with recovery (R2 = .62; P = .001). Because of the general availability of the HLA (LC) testing, the role of LC reactivity was investigated in other ways. There was a strong relationship between sera highly reactive by LC and those reactive by GIF. These highly reactive sera were also associated with reduced recovery and t1/2. The influence of specific HLA antigen mismatches was also studied. When donor and recipient were mismatched for the HLA-A2, B8, or BW44 antigens, there was a significant reduction in either recovery, t1/2, or both. Tissue localization was studied by body scans in patients with and without known sites of inflammation. Antibodies detected by a combination of GA and GIF caused abnormal pulmonary sequestration of granulocytes (three cases) and failure of granulocytes to localize at known sites of inflammation (three cases). HLA (LC) antibodies did not alter tissue localization despite the presence of the corresponding HLA antigens on granulocytes. It appears that GA, GIF, or a combination of these tests is the most effective predictor of altered in vivo fate of granulocytes. However, sera highly reactive by LC and GIF probably define a group of highly immunized patients in whom granulocyte recovery and t1/2 are also reduced. Mismatching for certain HLA antigens is also associated with reduced granulocyte recovery and survival. At present, GA, with or without the immunofluorescence assay, is the most effective predictor of altered in vivo granulocyte activity.(ABSTRACT TRUNCATED AT 400 WORDS)


2004 ◽  
Vol 78 ◽  
pp. 643
Author(s):  
K K. Mahawar ◽  
A M. Bal

1989 ◽  
Vol 26 ◽  
pp. 86
Author(s):  
R.M Radvany ◽  
M.R Costanzo-Nordin ◽  
M.J Zucker ◽  
L.A Nonn ◽  
R Pifarre ◽  
...  

2017 ◽  
Vol 1 (11) ◽  
pp. 669-680 ◽  
Author(s):  
Francesca Lorentino ◽  
Myriam Labopin ◽  
Katharina Fleischhauer ◽  
Fabio Ciceri ◽  
Carlheinz R. Mueller ◽  
...  

Key Points In unmanipulated haplo-HSCT, antigenic HLA-DRB1 match, stem cell source, conditioning, and donor sex are associated with GVHD. The role of HLA-matching status and other factors influencing alloreactivity is more prominent with PTCy compared to ATG GVHD prophylaxis.


2008 ◽  
Vol 86 (Supplement) ◽  
pp. 201-202
Author(s):  
L Vu ◽  
L A. Baxter-Lowe ◽  
J Garcia ◽  
M McEnhill ◽  
P Stock

2018 ◽  
Vol 52 (2) ◽  
pp. 1701898 ◽  
Author(s):  
Olivier Brugière ◽  
Antoine Roux ◽  
Jerome Le Pavec ◽  
Deborah Sroussi ◽  
François Parquin ◽  
...  

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4159-4159
Author(s):  
Patali Shikhi Cheruku ◽  
Veronica H. Jude ◽  
Renee M Madden ◽  
Charles F. LeMaistre ◽  
Ka Wah Chan ◽  
...  

Abstract Abstract 4159 Limited data is available on the role of ethnicity on outcomes after umbilical cord blood transplants (UCBT). This study retrospectively analyses the role of donor and recipient ethnicity on clinical outcomes after UCBT. All patients (pts) had UCBT at the Texas Transplant Institute in San Antonio where Hispanics make up a large proportion of pts undergoing UCBT. Pts had UCBT between 2001 and 2010. CIBMTR and hospital records supplied the data and included 260 pts who were: White (76), Hispanic (141), Black (19) and Asian (6). Blacks and Asians were excluded from analysis due to small numbers. Characteristics of Whites and Hispanics are described in table. Age, cell dose, myeloablative and non-myeloablative conditioning regimens, and single (s) and double (d) UCBTs were similar between the two ethnicities. More Whites (88%) had UCBT for malignant disease than Hispanics (68%) (p<0.001). Incidence of graft-versus-host disease (GVHD) was similar between Whites (acute GVHD grades II-IV: 44%, grades III-IV: 15%, limited chronic GVHD: 9% and extensive chronic GVHD: 11%) and Hispanics (acute GVHD grades II-IV: 34%, grades III-IV: 22%, limited chronic GVHD: 28% and extensive chronic GVHD: 15%) and regardless of whether they had malignant or non-malignant disease, standard (CR1, CR2 and CML-CP) or high (all others) risk hematologic malignant disease, s or d UCBT, and age. Disease and non-disease related mortalities (DRM and NDRM) were similar between Whites (DRM: 20% and NDRM: 23%) and Hispanics (DRM: 16% and NDRM: 24%) and regardless of whether they had malignant or non-malignant disease, high or standard-risk malignant disease, s or d UCBT, and age. Overall survival (OS) was similar between Hispanics (73.7 months) and Whites (70.2 months) and regardless of whether they had malignant or non-malignant disease, high or standard-risk malignant disease, s or d UCBT, and age. Hispanics had a longer OS (88.7 months) than Whites (68.5 months) when each received an ethnically matched s UCB product (p=0.030) and a shorter OS (43.3 months) than Whites (OS=not evaluable (NE), all patients alive) when each received an ethnically mismatched s UCB product (p=0.004). Hispanics with an ethnically mismatched s UCB product and malignant disease had a shorter OS (47.4 months) than Whites (NE, all patients alive) (p=0.016). Whites and Hispanics with ethnically matched and mismatched s UCB products had similar numbers of patients with malignant and high-risk malignant disease. Only 6 of the 163 Whites and Hispanics who had s UCBT were adults (≥18 years). Improvement in OS in Hispanics with ethnically matched s UCB products was related to an increase in OS from NDRM while worse OS in Hispanics with ethnically mismatched s UCB products was related to decreases in OS from both DRM and NDRM. There was a trend to longer OS among all pts with ethnically matched (82.3 months) versus mismatched (68.5 months) s UCB products (p=0.154). OS was shorter among all Hispanics with mismatched (43.3 months) versus matched (88.7 months) s UCB products (p=0.001). Cell dose, degree of HLA-matching, and percent with malignant and non-malignant disease were similar for all pts and between Whites and Hispanics with ethnically matched and mismatched s UCB products. In conclusion, ethnic mismatches between donor and recipient appear to affect survival in pediatric s UCBT. The effect of ethnic mismatches was more pronounced in Hispanics than Whites. Table: CHARACTERISTICS AND OUTCOMES White Hispanic Number of patients 76 141 Median age at transplant, years (range) 9.0 (0.1–79.2) 8.0 (0.1–61.7) Age category, years <18 61 (82%) 116 (82%) ≥18 13 (17%) 21 (15%) Median weight, kg (range) 25 (4–111) 26.3 (4–160) Recipient sex male 43 (57%) 90 (65%) female 31 (41%) 50 (35%) Transplant type single 57 (76%) 107 (76%) double 18 (24%) 34 (24%) Recipient CMV status positive 24 (32%) 61 (43%) negative 27 (36%) 41 (29%) *Malignant disease 66 (88%) 96 (68%) Donor/Recipient ethnicity match, s UCB matched 39 (70%) 57 (53%) mismatched 10 (18%) 28 (26%) HLA-matching, s UCBT 6/6 14 (25%) 9 (8%) 5/6 28 (56%) 50 (47%) 4/6 13 (23%) 44 (41%) Median cell dose x 10'37 TNC/kg (range) 5.7 (1.5–28.5) 5.6 (1.5–45.5) Median days ANC >500/μL 21 (10–50) 20 (10–100) Median days platelets >20K/μL 51 (24–165) 47 (21–167) Median days platelets >50K/μL 60 (29–137) 49 (24–224) Overall survival, months 70.2 73.7 Median follow-up, months (range) 28 (.25–121) 25 (.25–69) * p-value < 0.05 Disclosures: Shaughnessy: Otsuka: Honoraria, Speakers Bureau; Millenium: Honoraria, Speakers Bureau; Genzyme: Honoraria, Speakers Bureau.


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