Acute Leukemias - Republican Scientific Medical Library

Relapsed Acute Lymphoblastic Leukemia
Nicole Lamanna, Melissa von Hassel, Mark Weiss
Contents
22.1 Introduction ................... 275
22.2 Bone Marrow Transplant in Adult
Acute Lymphoblastic Leukemia ..... 276
22.3 Philadelphia Chromosome-Positive
Adult Acute Lymphoblastic Leukemia 277
22.4 CNS Relapsed in Adult Acute
Lymphoblastic Leukemia ......... 277
22.5 Newer Agents .................. 278
22.6 Conclusions ................... 278
References ......................... 278
22.1 Introduction
Treatment of acute lymphoblastic leukemia in children
is one of the great success stories of combination chemotherapy.
Unfortunately, adults fare much worse and
the majority of adult patients ultimately fail their initial
treatment program. Most current induction regimens
obtain complete responses (CRs) in 65–90% of
newly diagnosed adult patients with acute lymphoblastic
leukemia (ALL). Early deaths account for some
of the induction failures, but in most studies 10–25%
of patients have disease resistant to vincristine/prednisone-based
regimens. In addition to these primary
refractory patients, 60–70% of patients who achieve a
CR relapse. Treatment of relapsed and refractory patients
is therefore an important and common problem.
Numerous regimens have been reported in the setting
of relapsed ALL. There are two widely tested
approaches to reinduction therapy for adult patients
with recurrent or refractory ALL. One option is to
treat the patient with a regimen that is similar to their
original induction therapy (this strategy is obviously
not used for primary refractory patients). Combinations
of vincristine, prednisone, and an anthracycline
intensified with cyclophosphamide and/or L-asparaginase
represent traditional induction therapy, and variations
on this approach are employed frequently in
the salvage setting. Patients who have had a long first
remission or who develop recurrent disease after completing
maintenance chemotherapy occasionally can
achieve a second CR with a repetition of their initial
induction regimen [1].
Unfortunately most patients develop recurrent disease
within the first 12–24 months of achieving their
first remission, at a time when they are still receiving
maintenance chemotherapy [2–5]. For these patients,
the likelihood of achieving a second CR with reinduction
therapy similar to their initial regimen is low. In
addition, for the 10–25% of patients whose disease is
primarily refractory to standard induction therapy,
simply repeating the same induction treatments offers
essentially no hope of obtaining a CR. A second option
for these patients is to employ an active salvage regimen
that relies on agents that are relatively distinct from traditional
induction treatments. The most commonly
tested regimens of this type are based on high-dose cytarabine,
which, as a single agent, may induce a CR in
approximately 30% of patients with recurrent or refractory
ALL. In combination with other agents, particularly
anthracyclines, high-dose cytarabine-based regimens
appear to yield even higher response rates.