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

A. Bacigalupo
Ospedale San Martino,
Genova, Italy
Hematology Education:
the education program for the
annual congress of the European
Hematology Association
2011;5:51-55
Alternative donor stem cell sources
Unrelated donor transplants
Introduction
The issue of matching between donor and
recipient has been crucial from the origin of
clinical transplant activity, but the concept
has evolved over many years, with an
increasing level of sophistication (Table 1).
The methods of HLA typing have changed
from serological identification to molecular
techniques. Thus, the definition of a
matched donor in the eighties and nineties is
different from the definition of a matched
donor today. We used to match for the A, B,
DR locus at the antigenic, or serologically
determined, level, and a 6/6 match would
have identified a donor matched with his
recipient for six antigens (two on each of the
A, B, DR loci). We then started to use molecular
methodology for HLA-DR typing, but
were still calling this a 6/6 match. A 5/6
match would have been a donor with one of
the antigens mismatched.
Currently, we are matching for A, B, C,
DRB1 at the allelic level, that is with molecular
subtyping of the antigens, looking for
8/8 matched donors (Table 1). Some centers
are typing also for DQ looking for a 10/10
match and some others also for DP, looking
for a 12/12 matched donor. In an elegant
paper, Petersdorf et al. have shown that
beyond allelic matching, one can also match
for haplotypes. A donor and recipient can be
matched by phenotype (presence of the
same antigens on locus A, B, C, DR) but
mismatched by haplotypes. This study
showed that matching for haplotypes significantly
reduces the risk of GvHD, and this is
probably due to the fact that haplotype
A B S T R A C T
Unrelated donor stem cell transplantation was introduced into clinical practice in the 1980s and is
now more frequently performed worldwide than sibling transplant. The inherent increase in both major
and minor histocompatibility increases the complexity of the procedure and in unmanipulated grafts,
results in an increase in the risks of graft rejection and graft versus host disease. In contrast, the
enhanced alloimmunity leads to a reduction in disease recurrence. Improvements in the methodology
of HLA-typing and thus in donor selection, and in patient selection have resulted in steady improvements
in outcome since inception. The overall availability of donors and the speed of identifying suitable
donors remain a challenge to the success of this technique. On-going controversies include the
optimal source of stem cells (blood or bone marrow) and optimal graft versus host disease prophylaxis.
More recently, data have become available regarding donor safety, further underlining the need for
appropriate patient and donor selection.
matching indicates that a greater part of
chromosome 6 is matched between donor
and recipient. Finally, mismatching can be
permissive or non permissive: some studies
have shown that mismatching at specific
aminoacidic positions may be conductive to
more GvHD. 2,3
Bone Marrow Donors Worldwide (BMDW),
based at Leiden University, compiles different
national databases (registries) in one single
file. The initial resistance to the creation
of one single registry rather than individual
national registries was won by the scientific
stature of the founder, Jan van Rood. Today,
BMDW is a potent, fast, and up-to-date tool,
comprising over 15,000,000 volunteer
donors. It has proved to be clinically useful (a
preliminary search is done on line in “real
time”), but is also scientifically relevant,
since the large number of individuals represented
allows for genetic insight in different
populations.
Challenges to unrelated
transplantation
Finding a donor
The time to identify a donor depends on
the HLA of the patient (a common HLA will
lead to larger number of potential donors),
whether there is a fast lane for a specific disease
(acute leukemia) or disease phase, and
whether the transplant center is willing to
accept a donor who is less than a perfect
match. The time to identify a donor is as little
as 30 days to as long as many months. An
unrelated donor transplant should ideally be
considered early in the course of the disease.
Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1) | 51 |