NcXHF

MANAGING OLDER PATIENTS WITH ALL
TABLE 2. Outcome Data Concerning Older Patients with Acute Lymphoblastic Leukemia
Group/Study
Age
No. of
Patients CR Rate (%) OS (at 3 to 8 Yrs) Author
UK NCRI 55-64 100 70 19% at 8 yrs Sive 2012
CALGB 60 129 57 12% at 3 yrs Larson 2005
MD Anderson 60 44 79 17% at 5 yrs Kantarjian 2000
SWOG 8419 50-84 85 41 Not reported Petersdorf 2001
GIMEMA 0208 50-60 121 68 15% at 8 yrs Annino 2002
PETHEMA ALL96 56-67 33 58 39% at 5 yrs Sancho 2007
SWOG 9400 50-65 43 63 23% at 5 yrs Pullarkat 2008
EWALL 56-73 40 85 Not reported Gokbuget 2008
Abbreviations: CR, complete remission; OS, overall survival; Yrs, years.
data in patients who are less intensively treated. It is likely
that some of those patients will also be MRD negative; this
gives the option of escalating or de-escalating therapy. Most
available MRD data uses molecular techniques; MRD data
using flow cytometric techniques require further standardization
and prospective evaluation. This latter technology is
more frequently used in the United States.
UNITED KINGDOM DATA
Issues with the Data
Fewer patients in this age group are enrolled in trials, and they
are clearly a selected group and are probably unrepresentative of
newly diagnosed older patients with ALL. The chance of early
death is high as is refractoriness to chemotherapy.
FIGURE 1. Survival of Adults with Acute
Lymphoblastic Leukemia by Age Group
Adapted from Rowe JM et al. Blood. 2005;106:3760-3767.
SIVE ET AL
The United Kingdom Medical Research Council (MRC)/
Eastern Cooperative Oncology Group (ECOG) collaborative
group reported outcomes of therapy in 100 patients older
than age 55 out of a total of 1,914 recruited to United Kingdom
ALL XII/ECOG2993 (median age 56, range 55 to 65). 10
Patients were treated with the full protocol as detailed in
Goldstone et al, 7 with no planned dose reductions. Compared
with younger patients on study (younger than age 55),
more were female, Ph-pos (28% vs. 17%, p 0.02) and
slightly more were in a high-risk cytogenetic group (46% vs.
35%, p 0.07). The chance of CR was reduced by 20% (73%
vs. 93%, p 0.001).
Strikingly, 5-year overall survival was 21% in the older
group compared with 41% in the younger group (Fig. 2). Induction
mortality was higher (18% vs. 4%) and infections
were more frequent (81% vs. 70%, p 0.05). A reported infection
was associated with higher mortality, particularly if it
occurred in both phases of induction. Bacterial infections
also occurred at a 50% greater frequency in the older age
group. Forty-six percent of older patients had dose reductions
compared with 28% in the younger group (p 0.0009).
The most common reason for dose attenuations was hepatic
derangement and asparaginase was the drug most often
omitted. Reductions in chemotherapy dose were not signifıcantly
associated with worse outcomes but numbers were
small.
Importantly, Sive et al concluded that the induction protocol
used in this study was too intensive for many older patients
with ALL. They further stated that stratifying patients
based on their disease risk and fıtness for therapy might be a
way of individualizing therapy; those who are less fıt should
be treated less aggressively. Although unproven, using MRD
to guide decision making may also be valuable.
ALL 60
Recognizing the lack of prospective data to inform decision
making, the United Kingdom National Cancer Research Institute
ALL group initiated a prospective study in patients
with ALL older than age 60 with the goal of informing how
physicians and patients use information about comorbidities
and performance status at diagnosis to determine therapy.
Comorbidity information is being collected using a variety of
tools that have been validated in other groups of infırm
patients including many with cancer. There is also a noninterventional
registration arm (of patients not wishing to
participate) that will enable the estimation of the proportion
of older patients with ALL willing to enter prospective
trials.
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