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Blood, 15 November 2001, Vol. 98, No. 10, pp. 3150-3155
TRANSPLANTATION
Bone marrow transplantation from unrelated donors: the impact of
mismatches with substitutions at position 116 of the human leukocyte
antigen class I heavy chain
Giovanni B. Ferrara,
Andrea Bacigalupo,
Teresa Lamparelli,
Edoardo Lanino,
Laura Delfino,
Anna Morabito,
Anna M. Parodi,
Cinzia Pera,
Sarah Pozzi,
Maria P. Sormani,
Paolo Bruzzi,
Domenico Bordo,
Martino Bolognesi,
Giuseppe Bandini,
Andrea Bontadini,
Mario Barbanti, and
Guido Frumento
From Laboratorio di Immunogenetica, Servizio di
Epidemiologia Clinica and Laboratorio di Biologia Strutturale, Istituto
Nazionale per la Ricerca sul Cancro; Dipartimento di Ematologia,
Ospedale San Martino; Medicina IV UO Oncoematologia Pediatrica,
Ospedale Gaslini; Registro Italiano Donatori di Midollo Osseo, Ospedali
Galliera; Dipartimento di Oncologia, Biologia e Genetica,
Università di Genova; Genoa, Italy; Istituto di Ematologia e
Oncologia Clinica, L. e A. Seragnoli; Servizio di Medicina
Trasfusionale, Policlinico S. Orsola, Bologna, Italy.
The hypothesis was tested that amino acid substitutions in specific
positions within human leukocyte antigen class I heavy chain would have
different impacts on transplant-related mortality (TRM) in patients
receiving transplanted bone marrow from unrelated donors. One hundred
patients and their unrelated donors were typed by sequence-based typing
for the human leukocyte antigen (HLA)-A, -B, and -C loci. All pairs
were matched for DRB1, DRB3, DRB4, DRB5, DQA1, and DQB1 loci. Forty
pairs were also matched at class I, and 60 pairs had one or more
mismatches at class I loci. It was found that substitutions at
positions 116 and 114 of class I heavy chain significantly increased
the risk for TRM in univariate and bivariate Cox analyses. Conversely,
no association between number of multiple mismatches or number of amino
acid substitutions and TRM was seen when positions 116 and 114 were
adjusted for. Variables predictive of TRM in multivariate Cox analysis
were number of cells infused, diagnosis (chronic myeloid leukemia
[CML] or non-CML), and amino acid substitution at position 116 or
152. The only variable predictive of severe acute graft-versus-host disease (GVHD) in multivariate Cox analysis was substitution at position 116. Actuarial risk for acute GVHD grade III-IV, TRM, and
relapse in pairs with substitutions at position 116 (n = 37) compared
to other pairs (n = 63) was, respectively, 36% versus 14%
(P = .01), 59% versus 28% (P = .001), and
25% versus 31% (P = .4). In conclusion these data
suggest that substitutions at position 116 of class I heavy chain
increase the risk for acute GVHD and TRM in patients who receive
transplanted bone marrow from unrelated donors.
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