FEATURE
Drawing First Blood
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for the years they were out of range of
immediate care.
Obviously, those are two very specific
cases, but they highlight one of the major
reasons for choosing splenectomy as
second-line therapy: the durability and
ability to go for longer periods without
treatment.
Dr. McCrae: You make a good point, Dr.
Kitchens. There are some younger adult
patients – missionaries or not – who say
to me, “Look, I don’t want to come to the
doctor’s office. I’m in a far, distant land
– it’s called college – and I never want to
see the doctor.” For certain patients, that
is their main concern; they don’t want to
worry about their platelet count in their
day-to-day life and they want the most
definitive long-term treatment, which is
splenectomy. I don’t try to talk them out
of it, but I just make sure that I present
the options. If for some reason I feel that
one option is better than another, I’ll push
them in that direction.
The point I always make when I
discuss management of ITP is that
every patient is different; you have to
individualize the therapy to the patient.
We operate in an era of guidelines
and flowcharts outlining how to treat
patients if they meet certain criteria.
That may work well for certain diseases
– particularly for oncologic diseases,
where there is an abundance of data from
randomized controlled trials – but ITP
is a rare condition. We are lacking headto-head comparisons of these different
therapeutic approaches. That’s why
individualization is so critical.
Dr. Kitchens: Absolutely. And honestly,
I believe that the mortality of ITP and
the incidence of fatal bleeding from ITP
is much lower than nearly all physicians
estimate. I realized this in my own practice
over the past two decades; very few deaths
occurred, and only in very complex cases.
This was supported in the literature: James
N. George, MD, and colleagues found that
the overall mortality of ITP is less than 5
percent, and operative mortality with splenectomy was less than 1 percent.1,2. Furthermore, 66 percent of the 2,623 patients with
one- to 153-month follow up experienced
a complete response, and relapse rates were
only a median of 15 percent.
Dr. McCrae: There are some interest-
ing data that I think are closing the gap
between rituximab and splenectomy in
terms of which approach offers the best,
most durable response. Newer studies
are showing that there are long-term
responses with rituximab. Last year, James
B. Bussel, MD, and colleagues published
results of upfront treatment with rituximab plus three cycles of dexamethasone
in patients who had ITP for less than
two years.3 After more than five years of
ASHClinicalNews.org
follow-up, about two-thirds of patients
experienced long-term responses, which
is comparable to response rates with
splenectomy.
Risk of infection is another area in
which rituximab may have an advantage.
Clearly, the overall risk of infection is
higher in splenectomized patients, but the
literature on rates of infection in rituximabtreated patients is more controversial. It
depends on whether a patient is vaccinated
prior to receiving rituximab; this may be
more commonly done in Europe, but I try
to vaccinate most patients in my practice
who plan to start rituximab. Occasionally,
patients do not respond well to rituximab
and need a splenectomy quickly, so
immunization of such patients after
receiving rituximab is not optimal.
Infection, though uncommon after
splenectomy, is definitely a concern,
and will remain a concern. Patients
undergoing splenectomy may need
prophylactic antibiotics and need proper
education about the risk of infection.
“TP is a rare
I
condition and
every patient is
different. In the
management of
ITP, you have to
individualize the
therapy to the
patient.”
—KEITH MCCRAE, MD
We’ve mentioned patient preference
– but what about cost? Looking at
rituximab, the cost, to my knowledge,
is about $20,000, though that depends
largely upon institutional agreements. I
suspect splenectomy is considerably more
expensive in most hospitals.
Dr. Kitchens: On the splenectomy side,
cost depends on the approach – with
laparoscopic splenectomy, there will be
a decrease in morbidity and mortality
which, as has been shown in meta-analyses, is already very low. In my experience,
though, there is not a great savings with
the laparoscopic splenectomy, as opposed
to the open surgical approach.
Another issue I hear from many
hematologists whom I have trained is,
in determining whether a patient even
needs therapy, how low is too low in terms
of platelet counts? Is a count of 45,000
platelets low enough to start rituximab or
to undergo splenectomy? In my opinion,
that patient doesn’t need anything with
those types of numbers. This feeds
into the idea of the hematologist as the
ultimate “therapeutic nihilist,” but I would
not subject any patient to either of those
treatments if their platelet counts were in
a safe range – especially now that we have
thrombopoietin-receptor agonists like
eltrombopag and romiplostim.
In my 40 years of doing this, there has
been approximately every variable you can
possibly imagine for deciding treatment –
gender, age, whether the patient has lupus
– but none of these variables has a major
impact on outcomes.
Dr. McCrae: The only factor that may
have some value is age – younger patients
respond better to treatment than older
patients. But I agree that ther