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

attainment of FDC post DLI. Interestingly, this study
identified that patients with delayed attainment of FDC
at day 100 showed superior DFS and OS compared with
those with FDC by day 100 but similar RFS to those
with delayed FDC. Deaths in those with early FDC
were mainly attributable to GvHD or post-transplant
complications, such as infection. 47
In practice, with the limited objective data available to
guide timing and dosage of pre-emptive DLI for falling
donor chimerism, local policy will operate regarding
institution of therapy. Additionally, the use of a variety
of RIC regimens by different transplant centers means
that treatment decisions should be guided by review of
local outcomes; better reporting and if possible,
prospective studies would add greatly to this field.
Hematological relapse
Data addressing management of patients relapsing
with MDS HSCT is scant; however, in general, the longterm
outlook for these patients is poor. Remissions, if
attained, are frequently transient. The main options for
therapy (following withdrawal of immunosuppression)
in this setting comprise DLI, chemotherapy, second
HSCT and supportive care only. Treatment with DLI
alone achieves (often temporary) responses in a minority
of patients with clear morphological relapse 48 and
therefore, some form of induction chemotherapy is usually
desirable in addition to DLI to improve outcomes
but has not been the subject of prospective studies. In a
report by Oran et al. of 63 patients relapsing with MDS
or AML post RIC HSCT, therapy consisted of
chemotherapy for aggressive relapse or DLI/second
HSCT for more indolent relapses – response rates were
in the region of 40–50% for chemotherapy or second
HSCT but no patients responded to DLI alone. 49
Remission re-induction with chemotherapy may be
consolidated by DLI or a second transplant – in the
handful of patients who have received a second transplant
in this setting, long-term remissions can be seen
(2-year actuarial survival 50% reported in this study,
where 18 patients received a second HSCT) but may be
offset by increased TRM from a second procedure, for
example, due to GvHD. 49
Standard induction chemotherapy may be used for reinduction,
but with the advent of newer therapies for
MDS, could these agents be effectively employed following
HSCT to treat and even prevent relapse? There is
emerging data from a Phase I trial of low dose 5-
Azacytidine post HSCT 50 supporting its tolerability and
potential for treatment of relapsed/refractory MDS, and
it has also been used in a small group of patients at risk
of relapse as a maintenance therapy, 50,51 with a dose of 32
mg/m 2 for 5 days and four cycles shown to be both tolerable
and safe. 51 However, larger scale, prospective, and
randomized studies are required to evaluate the efficacy
of these novel agents in such a setting in the future.
Other treatments, which may come to the forefront of
future therapy for relapsed myeloid disease post HSCT,
include immunotherapeutic strategies, for example, peptide
vaccination targeting leukemia-associated antigens,
such as the Wilm’s Tumor protein (WT1) 52-54 and whole
cell leukemia vaccination with CD80 and IL-2 genetically
modified leukemic blasts, 55-57 which is currently the
subject of a Phase I clinical trial at our institution.
London, United Kingdom, June 9-12, 2011
Conclusion
The landscape of therapy for MDS has undergone
considerable change over the last several years with
the advent of RIC HSCT and as a result of the increasing
arsenal of therapeutic agents that may be
employed. Improvements in prognostication increase
confidence in decision-making in this area, and with
discoveries in the fields of genetics and flow cytometry,
this continues to evolve. However, along with
these innovations come new challenges and questions
to be answered. The lack of good quality data from
prospective, randomized, controlled clinical trials
results in conflicting data garnered from small, single
institution studies. The focus of future studies in transplantation
for MDS should be to strive towards the initiation
of prospective trials to answer the most pertinent
questions for the patient with MDS considering
HSCT: what, when, and how?
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