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

of the aging process with respect to organ function, cognitive,
and functional status, as well as social resources.
Comorbidity and geriatric assessment may help to
screen these dimensions systematically and to develop
better models for decision making. It also helps to detect
unknown health problems and social factors, such as
dependency and depression.
For practical reasons, different steps for an age-based
stratification can be defined, such as the age of 55–60
years as a cut point for very intensive chemotherapy
and SCT with full conditioning. The cut point of 75
years is often used for the definition of old age.
For future treatment of older ALL patients, it will be
essential to distinguish between frail or unfit patients in
whom an unacceptable high mortality of induction therapy
has to be expected and fit patients who can tolerate
intensive chemotherapy. A third group are patients with
good general condition before onset of leukemia but the
presence of leukemia associated complications, who
may benefit from an extended pre-phase treatment
with intensive supportive measures in order to stabilize
their general condition. For decision making, the
patient’s wish and individual status, disease characteristics,
and the expected outcomes regarding early mortality
and long-term survival have to be considered and
discussed.
The major risk for older ALL patients treated with
chemotherapy is death due to infections. It is therefore
essential to provide intensive supportive care, including
G-CSF, anti-infectious prophylaxis, and environment.
All older patients need a comprehensive diagnostic
classification. The identification of the bcr-abl translocation
is crucial since even in very old patients, the use of
TK inhibitors offers a realistic chance of complete
remission with very limited toxicity.
The attempt to achieve a remission should be made
whenever possible. Specific risks, such as the prolonged
use of steroids or asparaginase in induction, should be
avoided. On the other hand, there is still space for intensification
of chemotherapy particularly during consolidation
for fit patients. This includes the use of asparaginase
and RIC transplantation. It will be crucial to identify
prognostic factors for older ALL patients to define
indications for SCT. In unfit older patients, a minimal
induction and consolidation therapy is recommended
with the aim to control the disease. In both groups the
use of targeted therapies, such as Nelarabine, TK
inhibitors, antibody treatment, or new drugs with
potentially reduced or alternative toxicity will be essential.
Persistence of MRD is one of the most important
risk factors in ALL. Therefore, MRD evaluation should
also take place in older patients to identify those who
could benefit from experimental therapies.
A population based study from the US compared survival
data of two periods (1980–1984) and (2000–2004).
Most improvement was achieved in younger patients
aged 15–29 years, whereas in older patients above 60
years, the survival rates remained nearly unchanged
with 8% versus 13% relative survival at 5 years. 54
Whereas the current discussion has a strong focus on
treatment optimization in adolescents and young
adults, management of older ALL patients remains an
unmet medical need. Prospective trials specifically
designed for older ALL patients are needed, and patients
should, whenever possible, be entered in trials or registries
since otherwise, there is no gain of knowledge
and no chance of treatment optimization.
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