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

Table 4. A risk-based approach to develop individualized
management plans for myelofibrosis.
London, United Kingdom, June 9-12, 2011
as a thorough understanding by the patient of the complexity
and potential adverse effects of the therapy they
might choose to undertake.
Analysis of recent large series of ASCT in MF is sobering
(Table 2), with TRM ranging from 10–30% (depending
on age, donor compatibility, and conditioning regimen)
and rates of acute GVHD (grades II–IV) ranging
from 10–60%. Rates of chronic GVHD are even higher,
with certain series reporting 85% of patients with grades
II–IV chronic GVHD. Overall survival ranges from 30–
60%; the largest retrospective IBMTR series suggests
about one-third of patients with MF who are transplanted
might expect long term disease-free survival. 27
Given the risks and unanswered questions in 2011,
which patients with MF should be transplanted? The
group of patients where the risk-benefit ratio appears
most favorable is those progressing towards blastic
transformation. Given the median survival of patients
after transformation is less than 3 months, 5 ASCT, if it is
at all an option, should occur before transformation
occurs.
Clinical trials with newer agents that still may have a
greater impact on the natural history of these diseases
are viewed with great interest, but their impact on natural
history is of course, by definition, uncertain. Finally,
therapies may help to delay the natural progression of
the illness, but this again remains uncertain and their
use depends on the scenario. In patients with earlier
myelofibrosis, there is increasing data suggesting interferon
alpha 2a may be a consideration (Table 3).
Individuals with higher risk disease, that is, specifically
an increase in blasts hypomethylationtherapy, may be a
reasonable option. 26,28
Goal of palliation
If palliation is the goal for the MF patient, then we
must determine what is it that we are trying to palliate.
For splenomegaly, I would refer you to the low risk section
as the initial option that we would consider. For
individuals who have failed other options, one might
consider a clinical trial next if available and appropriate,
and finally, in select scenarios of overwhelming
mechanical symptoms, we will consider splenectomy 29
or splenic radiotherapy. 30 With limiting toxicities of both
of these latter therapies being first for splenectomy,
short and long-term morbidity and mortality, thrombosis,
and hemorrhage in the perioperative setting, and
long-term complications of leukocytosis and thrombocytosis,
splenic radiotherapy leading to profound
cytopenias and short duration of response.
Anemia based palliation revolves around the use of
immunomodulatory drugs, thalidomide, 31 lenalidomide,
32 and now pomalidomide 33 with individuals who
have a deletion 5q 34 in their cytogenetic profile being the
clearest candidates for lenalidomide therapy. The selective
use of erythropoietin for individuals with an inadequate
erythropoietin response is a reasonable option for
intermediate risk myelofibrosis patients. Androgen
based therapy, simply agents, such as danazol, 35 are reasonable
considerations. Clinical trials, specifically trying
to improve anemia, remain of interest but clearly have
an experimental endpoint.
And finally, for generally symptomatic burden, I
would refer you to the low risk section, as it would
Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1) | 269 |