Acute Leukemias - Republican Scientific Medical Library

Recent Clinical Trials in Acute Lymphoblastic Leukemia
by the Cancer and Leukemia Group B
Richard A. Larson, Daohai Yu, Ben L. Sanford, Wendy Stock
Contents
10.1 Introduction .................... 137
10.2 CALGB Study 8811 ............... 137
10.3 CALGB Study 9111 ............... 138
10.4 CALGB Study 9311 ............... 140
10.5 CALGB Study 9511 ............... 140
10.6 CALGB Study 9251 ............... 141
10.7 CALGB Study 19802 .............. 142
10.8 CALGB Study 19801: T-cell ALL
in Relapse ...................... 143
Acknowledgments ................... 143
References ......................... 144
10.1 Introduction
The Cancer and Leukemia Group B (CALGB) has performed
a series of studies evaluating different aspects
of induction and postremission treatment in adults with
acute lymphoblastic leukemia (ALL). In recent years,
these clinical trials have been supplemented by systematic
morphologic, immunophenotyping, cytogenetic
and molecular genetic studies, leading to the identification
of different risk groups of patients who may warrant
individualized treatments. Importantly, these protocols
have enrolled all adult patients older than 15 years
with ALL without an upper age restriction and did not
exclude Philadelphia (Ph) chromosome positive patients.
Between 1988 and 2001, the CALGB enrolled and
treated 759 adults with untreated acute lymphoblastic
leukemia (ALL) on one of five clinical trials using intensive
multiagent therapy. The median age was 36 years
(range 16 to 83 years); < ˆ 17% were 60 years old. Of 276
centrally reviewed and evaluable cases, 28% were Ph
chromosome positive; 5% had a t(4;11). Overall, complete
remission (CR) was achieved in 81% of the patients
[611/759, 95% confidence interval (CI), 78–83%]. The
median disease-free survival (DFS) measured from time
of CR was 2.0 years (95% CI, 1.6–2.3 years), and the
median overall survival was 2.0 years (95% CI, 1.7–2.3
years). At 3 years, 40% (95% CI, 36–44%) remained in
continuous CR, and 41% (95% CI, 37–44%) were still
alive. Age was a strong determinant of patient outcomes
as shown in Figs 10.1 and 10.2.
10.2 CALGB Study 8811
Intensive multiagent chemotherapy programs produce
CRs in the majority of adults with ALL. CALGB study
8811 built upon observations by the CALGB and others
that a more intensive remission induction program
might produce more durable responses [1]. A single
dose of cyclophosphamide (1200 mg/m 2 ) was added to
a modification of the four-drug regimen (daunorubicin,
vincristine, prednisone, L-asparaginase) used in earlier
CALGB studies (7612 and 8011) [2, 3]. The treatment
schema is shown in Table 10.1. In addition, a more intensive
program of L-asparaginase administration was
used during induction and the first 2 months of postremission
consolidation because of reports suggesting the
importance of intensive asparaginase therapy in chil-