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

etween 1995 and 2005. 11 Five hundred and thirty-five
MDS patients (aged 40–78 years) and 545 AML patients
(aged 40–79 years) from 148 centers underwent RIC or
non-myeloablative (NMA) HSCT (although predominantly
RIC). Patients over the age of 65 accounted for
only 12% of the AML and 10% of the MDS cohort,
underlining the low numbers of HSCT performed in
this age range. The authors surmised that the low numbers
are due to lack of data regarding outcomes for older
patients undergoing HSCT and as a result, fewer referrals
for this procedure within this age group.
Significantly, there was no effect of recipient age on
NRM, DFS, or OS in either the AML or MDS patient
groups and 2-year survival was 30% across the ages,
confirming the potentially curative role of HSCT for
these diseases.
Such studies highlight the different conditioning regimens
used worldwide (Figure 1) and indeed, the variation
within regimens classified as SMC, RIC, or NMA.
The distinctions between the categories are not clearcut:
under the umbrella of RIC conditioning, some regimens
may be more or less myeloablative than others, 12
for example, those regimens using more than 10 mg/kg
of busulphan versus less than10 mg/kg busulphan, 13 and
this should be borne in mind when considering data collected
from multiple, or even single, centers. Newer
agents, such as treosulfan, are also being explored in
RIC regimens, and one retrospective study showed an
improved estimated 3-year RFS for patients undergoing
HSCT conditioned with treosulfan (54%) versus 11%
with total body irradiation-based conditioning. 14 The
considerable variation between treatment regimens
adds to the complexity of interpreting outcomes for
“RIC” or “NMA” transplantation.
In summary, current data suggests that with the
advent of RIC, age alone is not a barrier to HSCT in
older patients and this procedure may be curative, with
an acceptable NRM. With advancing age however,
comes the attendant increased possibility of disease
refractoriness to therapy and this remains an additional
hurdle to overcome in the treatment of the older patient
with MDS: the number of such patients who will enter
a remission long enough to proceed to HSCT remains
small. For those patients who can undergo HSCT, there
is still an absence of data from randomized controlled
clinical trials in this area to confirm the OS benefit and
this should be a focus of future research.
Comorbidity
Since the majority of patients with MDS are in their
6th or 7th decade of life, it is to be expected that this
patient group will be afflicted by comorbid conditions
that may have an impact upon outcome following
HSCT. Whilst clinical investigation of organ function
provides objective data upon which to form opinions
regarding a candidate patient’s suitability to undergo
HSCT, it is natural for there to be subjective biases
which may influence this decision and lead to variations
and selection bias between physicians. To standardize
assessments of patients’ suitability for HSCT, it is therefore
useful to employ a scoring tool that not only identifies
patients with greater relevant comorbidities, but
also has sufficient prognostic impact to identify those
patients for whom HSCT (irrespective of conditioning
London, United Kingdom, June 9-12, 2011
strength) has unacceptably high NRM. Universal adoption
of such scores in analyses of outcomes of HSCT
will also enable greater ease of comparison between
studies.
Several comorbidity scores have been used to assess
patients prior to transplantation previously, 15-17 but have
limitations in that they may not have been developed
specifically to evaluate patients undergoing HSCT for
hematological malignancy or were developed in the era
of SMC HSCT and therefore, may not be applicable to
the predominantly older patients now undergoing RIC
HSCT. A single scoring system may not be valid in the
setting of transplantation for different malignant hematological
diseases and this would need to be prospectively
evaluated.
There has been considerable interest in the Haematopoietic
Cell Transplantation Comorbidity Index (HCT-CI), 18
which has been demonstrated to provide prognostic
information not only for patients with MDS undergoing
transplantation, but also in those unsuitable for transplantation.
19 When specifically applied to patients with
MDS or AML undergoing NMA or SMC HSCT, Sorror
et al. (Table 2 and Figure 1) showed in a retrospective
analysis that HCT-CI score was a strong predictor of
worse outcome following HSCT at multivariate analysis
(along with poor risk cytogenetics and high risk disease).
20 Additionally, patients could be stratified according
to HCT-CI score and disease risk, with increasing
NRM in patients with higher HCT-CI score and higher
risk disease. Those patients with highest HCT-CI score
and higher risk disease also suffered the worst OS (29%
at 2 years) irrespective of conditioning regimen, with
the reduced NRM of NMA HSCT being offset by an
increased risk of relapse. Prospective use of HCT-CI and
disease risk in clinical trials to analyze outcomes post
RIC, NMA, and SMC HSCT are highly desirable.
There is limited data regarding the use of HCT-CI in
MDS patients undergoing RIC HSCT. A retrospective
analysis from our institution examined outcomes for 128
patients undergoing RIC HSCT (sibling and unrelated
donors) with a uniform alemtuzumab-based conditioning
regimen for high risk MDS and AML. 21 Patients with
HCT-CI greater than or equal to 3 had the greatest NRM
(42% at 3 years), thus defining a sub-group of patients
for whom RIC HSCT may not be the optimal treatment
option, especially with the emergence of novel therapeutic
agents but this too requires evaluation prospectively.
Iron overload
An additional factor to be considered with regards to
comorbidity in patients with MDS undergoing HSCT is
the impact of iron overload secondary to repeated transfusion.
An elevated serum ferritin (>1000 μg/L) has been
associated with reduced OS and increased risk of infection
(fungal and bacterial) following HSCT, largely in
analyses of SMC HSCT patients. 22,23 Ferritin alone is considered
an unsatisfactory marker of iron overload, given
that as an acute phase reactant, it will be elevated in the
presence of inflammation; for this reason, an evaluation
of degree of transfusion dependency along with other
biomarkers of body iron load add further impact to the
suggestion of a detrimental impact of repeated transfusion
on outcomes post HSCT. A recent retrospective
analysis by the Gruppo Italiano Trapianto di Midollo
Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1) | 237 |