NcXHF

DAVID I. MARKS
who received RIC allografts will be discussed later in the
manuscript.
GERIATRIC ASSESSMENT, RECOMMENDATIONS FOR
ADJUSTED THERAPY, USE OF NEW AGENTS
A thorough pretreatment assessment of comorbidities is important.
Diabetes and prior malignancy are commonly seen. 5
These objective geriatric assessments have become more formalized
recently. 11 On the basis of simple, easy-to-apply criteria
(e.g., activities of daily living, performance status,
assessment of cognition, and physical function), patients can
be divided into three categories: fıt, vulnerable, and frail.
Some very simple individualized adjustments to treatment
can make treatment effective and tolerable. Shortening the
period of neutropenia with granulocyte-colony stimulating
factor (G-CSF) is sensible, and one study showed that this
resulted in improved survival. 12 Some older patients are unable
to tolerate the combination of prolonged neutropenia in
the presence of steroids and require omission or dose reductions
in myelotoxic drugs. If these drugs are omitted, physicians
should consider using rituximab in patients with
CD20-positive B-cell disease. Two randomized trials are currently
evaluating rituximab’s effıcacy, but historic control
data are encouraging. 13
Asparaginase is more likely to cause severe hepatic dysfunction
especially in the presence of hepatotoxic drugs such
as omeprazole, cotrimoxazole, and imatinib. Asparaginase
should be used sparingly, if at all, in patients older than 60
and with very careful monitoring.
Patients with signifıcant smoking histories and concomitant
cardiac and pulmonary dysfunction tolerate sepsis
poorly. Although its use remains controversial, use of quinolone
prophylaxis, G-CSF, and very early treatment of possible
sepsis is recommended.
The use of agents such as blinatumomab may be an effective
means of eliminating MRD with less immune suppression,
but large scale effıcacy data are lacking in older patients
as are tolerability data, especially with regard to central nervous
system toxicity. 14 Nelarabine may be an important adjunct
up-front in T-cell disease; 15 United Kingdom ALL XIV
is examining this issue. Inotuzumab has been examined in a
phase III comparison with standard of care therapy in relapsed
disease; this trial should yield important safety and effıcacy
data in patients older than age 50. 16-17
PH-POS ALL
Ph-pos ALL will be only discussed briefly as it will be dealt
with in detail in a subsequent manuscript. One-quarter of all
adults are Ph-pos, and the incidence is approximately 50% in
patients older than age 50. Until the results of recent studies
in older patients became available, most patients with Ph-pos
ALL were managed with intensive chemotherapy and a tyrosine
kinase inhibitor. Imatinib has improved the CR rate in
a number of trials to greater than 90% and makes more patients
eligible for transplant. 18 Imatinib resistance mutations
are increasingly reported, and these should be sought in patients
with relapsed and refractory disease.
Nearly all older patients with Ph-pos disease should be
treated with a TKI, vincristine, steroid, and possibly reduceddose
anthracycline. If they achieve CR, subsequent therapy
should be individually tailored depending on toxicity, comorbidities,
and, possibly, MRD status. B-cell antibodies are
also worth considering in this age group; rituximab is well
tolerated. This de-escalation of therapy is well tolerated and
highly effective in the short term, but data are lacking regarding
medium- to long-term survival. An alternative and very
effective strategy in older patients is to use dasatinib alone or
with steroids. 19
ISSUES OF SUPPORTIVE CARE
Infection
Unless the patient has a contraindication to quinolones, such
as past Clostridium diffıcile infection, they should be used in
this patient group as bacterial infection is a common cause of
death in induction. Similarly, G-CSF should be routinely
used to mitigate neutropenia. There is randomized controlled
evidence to support this practice, albeit from an older
study. Antifungal prophylaxis should be considered during
induction chemotherapy, but azoles need to be used carefully
to avoid excess vincristine toxicity.
HEPATOTOXICITY
Some patients older than age 50 will be treated with asparaginase;
this is the major cause of induction-associated liver
dysfunction. There is an association between inductionassociated
liver dysfunction and anthracycline use and possibly
with imatinib. Patients are generally given asparaginase
in the third week from the start of chemotherapy. Liver function
tests should be carefully monitored, and asparaginase
should not be given to patients with signifıcantly abnormal
liver function tests. Hepatotoxic drugs such as cotrimoxazole,
omeprazole, and many antifungals should be stopped.
RENAL DYSFUNCTION
Many older patients have abnormal baseline renal function.
Careful attention should be paid to hydration and the avoidance
of nephrotoxic drugs unless there is no alternative. Allowing
patients to become fluid overloaded can necessitate
the later use of furosemide, which depletes intravascular fluid
with downstream effects on the kidneys.
A ROLE FOR REDUCED-INTENSITY
ALLOGENEIC TRANSPLANTATION?
It may seem illogical to be contemplating reduced-intensity
allogeneic transplantation in a group of patients who tolerate
chemotherapy poorly; however, RIC allografting, if studies
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