H e m a t o lo g y E d u c a t io n - European Hematology Association

Table 2. The effect of HLA mismatch in unrelated donor transplants: representative studies.
the Japanese Donor Registry (JMDP) on 5210 patients,
found six specific amino acidic substitution positions in
the HLA class I that were associated with severe acute
GvHD: the authors refer to these as “non-permissive
mismatches”. 3 The positions are 9, 77, 80, 99, 116, and
156 (Table 2). One of these (116) had already been
reported as risk factor for GvHD. 2 Patients with a fully
matched donor (n=712) have the same risk of GvHD as
patients without non-permissive mismatches (n=2670),
but significantly less GvHD compared with patients
with one non-permissive (n= 602) or two non-permissive
(n=66) mismatched donors.
Petersdorf et al. showed that matching donor and
recipient for haplotypes reduces GvHD and TRM 1
(Table 2). In keeping with this result, survival in excess
of 90% has been reported for thalassemia patients,
prospectively assigned to receive transplants from UD,
matched by ancestral haplotypes: this study was possible
because the patients were from the island of
Sardinia, known to be homogeneous by HLA typing,
and ancestral haplotypes are common in the population.
12 Because of the protective effect of GvHD on
leukemia relapse, haplotype matched pairs experienced
more leukemia recurrence and survival was similar
overall in matched/mismatched pairs. 1 However, in
patients with early disease, or in patients with non
malignant disorders, one may wish to transplant from
haplotype matched donors with little risk of GvHD and
TRM. In patients with advanced disease, a partially mismatched
donor may also be acceptable, or perhaps
preferable.
An innovative approach to hematopoietic stem cell
donor-recipient matching consists in taking the conventional
allele-matching further to functional matching for
shared T cell epitopes (TCE) defined by in vitro alloreactive
cross-reactivity patterns. In this setting, allelic mismatches
not involving TCE disparity (i.e., the mismatched
alleles in both patient and donor are positive or
negative for the shared TCE) are considered to be permissive,
while allelic mismatches involving also TCE
disparity (i.e., the mismatched allele in the patient is
negative and in the donor is positive for the TCE, or vice
versa), are considered to be non-permissive in host versus
graft or graft versus host direction, respectively. In a
London, United Kingdom, June 9-12, 2011
Study Reference No. of patients Diagnosis Groups in which Mismatches
mismatching confers to be avoided
survival disadvantage
Seattle 10 1249 Leukemia Early disease C locus
NMDP CIBMTR 11 3860 AML ALL MDS CML Early disease A or DRB1
JMDP 3 5210 Malignant and non malignant All patients C locus
Non permissive mismatches
positions 9,77,80,99,116,156
Seattle 1 246 Leukemia All patients Haplotype
Mismatched
GITMO 13 537 Leukemia All patients DP non permissive mismatch
CIBMTR 14 1409 Leukemia AML Donor Cen B gene content