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. 2017 Apr 21;1(11):669-680.
doi: 10.1182/bloodadvances.2017006429. eCollection 2017 Apr 25.

The impact of HLA matching on outcomes of unmanipulated haploidentical HSCT is modulated by GVHD prophylaxis

Francesca Lorentino  1 , Myriam Labopin  2   3   4 , Katharina Fleischhauer  5 , Fabio Ciceri  1 , Carlheinz R Mueller  6 , Annalisa Ruggeri  2   3   4 , Avichai Shimoni  7 , Martin Bornhäuser  8 , Andrea Bacigalupo  9 , Zafer Gülbas  10 , Yener Koc  11 , William Arcese  12 , Benedetto Bruno  13 , Johanna Tischer  14 , Didier Blaise  15 , Giuseppe Messina  16 , Dietrich W Beelen  17 , Arnon Nagler  3   7 , Mohamad Mohty  2   3   4
Affiliations

The impact of HLA matching on outcomes of unmanipulated haploidentical HSCT is modulated by GVHD prophylaxis

Francesca Lorentino et al. Blood Adv. .

Abstract

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with unmanipulated grafts is increasingly adopted for high-risk acute leukemia, with acute graft-versus-host disease (aGVHD) prophylaxis based on antithymocyte globulin (ATG) or posttransplant cyclophosphamide (PTCy) as main platforms. No consensus exists on selection criteria over several haploidentical donors. We evaluated the impact of donor-recipient antigenic and allelic HLA-A, -B, -C, and -DRB1 mismatches on mismatched haplotype on outcomes of 509 unmanipulated haplo-HSCTs performed for acute leukemia under a PTCy (N = 313) or ATG (N = 196) regimen. An antigenic but not allelic mismatch at the HLA-DRB1 locus was an independent risk factor for grade ≥2 aGVHD in PTCy (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.2-4.0; P = .02) but not in ATG regimens (HR, 1.3; 95% CI, 0.4-3.4; P = .6). Moreover, the hazards of aGVHD were significantly associated with other factors influencing alloreactivity, including peripheral blood as stem cell source (HR, 2.2; 95% CI, 1.4-3; P < .01), reduced-intensity conditioning (HR, 0.6; 95% CI, 0.4-0.9; P = .04), and female donors (HR, 1.8; 95% CI, 1-3.2; P = .05), in PTCy but not ATG regimens. No significant associations were found between cumulative number of HLA mismatches and GVHD, or between HLA-matching status and other study end points including transplant-related mortality, disease-free survival, and relapse. Based on these data, the role of HLA mismatching on unshared haplotype appears not to be sufficiently prominent to justify its consideration in haploidentical donor selection. However, the role of HLA matching in haploidentical HSCT might be modulated by GVHD prophylaxis, calling for further investigations in this increasingly relevant field.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Influence of HLA-DRB1 matching status on aGVHD 2-4 in PTCy regimens. (A) Stratification according to antigenic HLA-DRB1 matching (N = 313). (B) Stratification according to allelic HLA-DRB1 matching (N = 258).
Figure 2.
Figure 2.
Influence of the number of HLA-A, B, C, DRB1 mismatches on aGVHD 2-4 in PTCy regimens. (A) Stratification according to the number of antigenic mismatches on the unshared haplotype (N = 313). (B) Stratification according to the number of allelic mismatches on the unshared haplotype (N = 258).
Figure 3.
Figure 3.
Influence of clinical variables on aGVHD 2-4 in unmanipulated HSCT. Stratification according to stem cell source (A,D), donor sex (B,E), and intensity of conditioning regimen (C,F) in PTCy regimens (A-C) or ATG regimens (D-F).
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