NcXHF

DAVID I. MARKS
TABLE 1. Prospective Studies of Acute Lymphoblastic
Leukemia in Patients Older Than Age 54
Author
Complete Remission
Rate (%)
Median Survival
(Months)
Kantarjian 1994 65 11
Bassan 1996 59 9
Delannaoy 1997 85 14
Delannaoy 2002 58 9
Offidiani 2003 73 Not stated
KEY POINTS
Older patients with ALL require an individualized
assessment of comorbidities and therapy adapted to their
performance status, disease response, and personal
treatment goals. Newer targeted therapies are likely to
play a larger role.
Optimal postremission therapies in older patients are
unknown as are their effects on quality of life and in
maintaining complete remission (CR). Reduced intensity
conditioning (RIC) allografting in fit patients who have
responded well to therapy and have high-quality donors
deserves further exploration.
Arguably, older patients with Philadelphia-positive (Ph-pos)
ALL have better outcomes than older patients with Phnegative
disease. This patient group can reliably achieve
CR with vincristine, steroids, and a tyrosine kinase inhibitor
(TKI) with minimal toxicity. Medium-term survival can be
achieved in many older patients with gentle maintenance
therapy and a TKI. Using a different agent at relapse may
prolong survival.
Internationally, ALL investigators need to target this
neglected group of patients by opening clinical trials that
ask questions aimed at improving survival and the quality
of that survival. Physicians who manage these patients are
urged to enter patients into these clinical trials so that we
can learn which therapy can be tolerated and is most
efficacious. These basic studies would provide the
background data that will enable study of newer targeted
therapies that have less marrow and extramedullary
toxicity.
should be stopped, if possible. Nutrition is a major issue; all
older patients should be seen by a dietitian and their diets
proactively managed.
One of the key treatment decisions in this age group is
whether an older patient can safely receive conventional
doses of anthracycline. A baseline echocardiogram with estimation
of ejection fraction is essential. However, many patients
will have had a past history of ischemic heart disease or
abnormal echocardiograms. Cardiac arrhythmias are common
pretreatment (and during induction) and may require
cardiac consultation and a change in therapeutic strategy. Liposomal
daunorubicin deserves further testing and liposomal
vincristine may result in less autonomic neuropathy.
GOALS OF THERAPY AND PHILOSOPHY
OF TREATMENT
Progress in ALL in older patients has been inhibited by a lack
of systematic prospective trials and a lack of consensus about
the goals of therapy. Only a small percentage of older patients
are enrolled in trials, 5 and these patients may not represent
the entire group. Prospective studies of older patients show
CR rates that range from 30% to greater than 70%, but median
survivals generally less than a year. Some studies using a
less aggressive treatment intent showed similar survival.
Their data may be informing us that one treatment does not
fıt all: that some are suitable for treatment with curative intent
but many are not.
Intensive, prolonged inpatient chemotherapy, with high
toxicity and a substantial NRM, can only be justifıed in this
age group within the context of a clinical trial or if there is a
signifıcant chance of at least medium term survival.
HOVON
The fairly small-scale data by the HOVON group highlights
the uncertainties of how to manage this disease. 9 In 24 patients
age 61 to 70 (who were undoubtedly highly selected),
79% achieved CR, and overall survival at 3 years was a remarkable
50%. However, the price for these results was 21%
induction mortality. Patients and physicians might accept
this NRM as it was accompanied by a realistic chance of
medium-term survival. Three of the 24 patients underwent
an allogeneic transplant.
POTENTIAL ROLE OF MINIMUM RESIDUAL
DISEASE
Eligibility for the United Kingdom ALL XIV trial is for people
age 65 or younger, although patients older than age 60
who are less fıt may be entered onto the United Kingdom
elderly patient trial (ALL 60). There are few prospective
minimum residual disease (MRD) data in the age 60 or older
group.
Of the 19 patients older than age 60 analyzed so far, only
three were MRD negative after phase I, but fıve of 16 were
negative after phase II (Zakout, unpublished data) with some
additional patients being very low-level positive. This shows
that intensively treated older patients can be rendered MRD
negative. How to use this very limited information is uncertain.
MRD-positive patients, depending on their clinical
well-being, could be informed of the result and given the
choice of therapy to attempt to render them MRD negative or
to receive more gentle palliative treatment.
Patients who are MRD-negative, on the other hand, would
be candidates for RIC allografts, further intensive chemotherapy,
or possibly even an autograft. We need further MRD
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