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

asparaginase (PEG), where the Escherichia coli is conjugated
to polyethyleneglycol, improved efficiency. 37-40
Given the longer half life and the lower risk of antibody
formation, 41 it is likely that this form of asparaginase
will replace the native source and will be included in
future trials of induction therapy in adult ALL.
As most patients get into morphologic CR, any
attempts to improve on this would be directed at reducing
the level of minimal residual disease (MRD), in the
hope that such reduction will ultimately impact on the
overall long term survival. Several new agents have
been introduced in the past few years for relapsed disease
and are currently being evaluated as adjunctive
therapy in induction. These include nelarabine for T-cell
ALL, 42 clofarabine for all ALL patient, 43 and liposomal
vincristine. 44 Inhibitors of purine nucleoside phosphorylase,
such as forodesine, are in early stage of development
and have the potential to improve the outcome,
especially in T-cell ALL. 45
Monoclonal antibody therapy is an attractive option to
consider in induction therapy for ALL. Some encouraging
data have been reported with the use of rituximab, a
monoclonal antibody to CD20, in the management of Bcell
ALL. 46 Epratuzumab, a monoclonal antibody to
London, United Kingdom, June 9-12, 2011
CD22 is thought to act by an immunomodulatory action
and is an important potential agent also for B-cell ALL. 47
Alentuzumab, an antibody directed against CD52, is a
monoclonal antibody with broad expression on most Tand
B-cell ALL patients. However, to date there are only
scant data on this in ALL. 48 Perhaps, the antibody with
the greatest potential is blinatumomab, which belongs
to a new class of bi-specific T-cell engagers (BiTEs). This
compound is a monoclonal antibody combining two
binding sites: a CD3 site for T-cells and a CD19 site for
the target B-cells. The drug works by linking these two
cell types and activating the T-cells to exert cytotoxic
activity on the target cell. Although preliminary, some
extraordinary results have been reported both in pediatric
ALL, 49 as well as in adult ALL. 50 In fact, the Eastern
Cooperative Oncology Group (ECOG) will shortly
embark on a prospective randomized study evaluating
blinatumomab in induction, with the aim of achieving a
greater degree of MRD negativity.
Mortality from induction, occurring in 3–8% of
patients, is also an important issue as this is due mostly
to opportunistic infections, such as Aspergillus. 14 This is,
in part, related to the prolonged exposure to glucocorticoids.
Substituting dexamethasone for prednisone and
reducing the overall period of exposure to glucocorticoids
will hopefully reduce the induction mortality further.
CNS prophylaxis
The incidence of CNS involvement at diagnosis is
about 4–7%. 51,52 Although such involvement portends
for a poor outcome, if treated appropriately at diagnosis,
the ultimate prognosis is not different from those
patients who presented without CNS involvement. 53,54
CNS involvement at first relapse occurs in about 30% of
adults without prophylaxis 55 and in only 5–15% of
those who got prophylaxis. 51,52
As CNS relapse carries a very poor prognosis, prophylaxis
is an imperative in the management of ALL. There
are three modalities of CNS prophylaxis: intrathecal (IT)
therapy, high dose systemic therapy that can cross the
blood-brain barrier (BBB), and radiotherapy. The main
drugs for the first two modalities are glucocorticoids,
methotrexate (MTX), and cytarabine. While the efficacy
of prophylaxis was established in the early 1980s, 55 the
best modality is still an open issue. In pediatric ALL,
dexamethasone was more effective in the prevention of
CNS leukemia than prednisome was. 56 Most of the adult
protocols currently combine IT MTX with high dose
therapy (MTX and/or cytarabine). Radiotherapy is a
very effective prophylaxis but is toxic for children and
can cause cognitive impairment in adults, especially in
patients over 60 years. 57,58 In a Spanish retrospective
study, the preventive results of IT plus systemic high
dose therapy were as good as other studies, which
included radiotherapy in their protocol. Thus, the issue
of radiotherapy remains open and most of the current
protocols omit radiotherapy as prophylaxis, 59 although
some reserve this modality for very high risk patients.
The ideal interval between IT treatments still has to be
established. A relatively new agent is liposomal cytarbine,
which when given IT, maintains elevated levels of
AraC in the CSF for at least 14 days, 60 thus requiring less
frequent IT administrations.
Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1) | 13 |