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

J.M. Rowe 1,2
C. Ganzel 1
1 Shaare Zedek Medical Center,
Jerusalem, Israel; 2 Technion, Israel
Institute of Technology, Haifa, Israel
Hematology Education:
the education program for the
annual congress of the European
Hematology Association
2011;5:9-19
Acute lymphoblastic leukemia
Management of acute lymphoblastic leukemia
in adults
The treatment of adults with acute lymphoblastic
leukemia (ALL) remains
challenging. While there has been a
gradual improvement in the overall results
over the past 40 years, the long term survival
from diagnosis for adults less than 60 years is
still no more than 35–40%. The therapeutic
options have increased over the past decade
to include a better understanding of the indications
for transplantation and a broadening
of the number of patients who are eligible
for such a procedure. New drugs, as well as
potential targeted monoclonal antibodies,
have opened up novel areas for study in the
management of ALL. Sensitive techniques
for the detection of minimal residual disease
have also opened new strategies for post
remission management. This paper will
focus on the management of young adults,
up to age 60 years, and will include both
patients who are Philadelphia chromosome
negative ALL, as well as those who are positive.
Most of the discussion will focus on
newly diagnosed patients.
Prognostic factors
At presentation
It has long been realized that the management
of patients with ALL is dependent on
the prognostic factors at diagnosis. Patients
with known very high risk features are often
assigned different post remission strategies,
even if the induction therapy is not always
altered. Decisions regarding the appropriateness
of bone marrow transplantation are also
dependent on the prognostic factors at diagnosis.
Over the past four decades, there has
been a shift in the understanding of the prognostic
factors such that morphology 1 and
cytochemistry, 2 so dominant in the 1970s,
have no prognostic significance nowadays.
Even immunophenotyping, which was the
dominant determining factor for several
decades since the 1980s, is rapidly becoming
less important for prognostication, even if its
use remains crucial for the initial diagnosis,
for the detection of minimal residual disease,
and for the application of specific and targeted
therapies. Thus, although B- and T-lineage
patients are often treated differently,
the level of maturity within B-lineage is no
longer important for prognosis, 3,4 although
among T-lineage patients, there appears to
be a difference depending on the level of
maturity. 5 At the same time, certain
immunologic markers have been recognized
as having significant prognostic impact, the
most important of these being CD20, which,
in several trials, has been reported among
adults with B-lineage ALL to have a low
complete remission rate and inferior overall
survival. 6,7 While these historic prognostic
factors clearly have relevance, they have
now been mostly superseded by genetic
and/or molecular markers leading to a
changing paradigm, incorporating cytogenetics
and molecular determinants 8 (Figure
1). The importance of immu no phenotyping
for assigning specific targeted therapies
against antigenic determinants for B or T-cell
ALL, such as nelarabine, foro desine, or monoclonal
antibodies, 9–11 will be fully discussed
in the Therapy section.
Age has withstood the test of time and
remains the most important prognostic factor
in ALL that is unlikely to be superseded
by any of the new molecular determinants.
Not only are there enormous differences in
prognosis between childhood and adult ALL,
but age also critically affects the prognosis
within adult groups. Although most clinical
studies have used an arbitrary cutoff of 35 or
40 years, 12–14 the prognostic significance of
age, in fact, is a continuum between ages 20
and 60. 14
The prognostic classification in ALL, much
like AML, is now moving rapidly towards
cytogenetics and molecular markers. The
Philadelphia chromosome, t(9;22) (q34;q11),
remains the most frequent and clinically significant
abnormality in adult ALL, with an
incidence that increases with age, reaching
50% among older adults with B-lineage. 15
The importance of determining the presence
of the Philadelphia chromosome at diagnosis,
either by cytogenetics or by molecular
detection of BCR-ABL, cannot be overstated,
as the entire approach to such a patient is
different (see Philadelphia chromosome-positive
ALL section). Among patients who are
Philadelphia chromosome-negative, management
is also affected by cytogenetics
(Table 1) and this categorization has a major
impact on choosing the appropriate therapy
for ALL. 16 In the past, due to the relative rarity
of ALL in adults, the precise prognostic
significance of many of the recurring cytogenetic
abnormalities could not be determined
due to the relatively small numbers. The
analysis of cytogenetics among patients
Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1) | 9 |