Acute Leukemias - Republican Scientific Medical Library

134 Chapter 9 · General Approach to the Therapy of Adult Acute Lymphoblastic Leukemia
zumab may therefore provide additional benefit to patients
with particularly T-cell leukemias or lymphomas.
The group at M.D. Anderson has started to incorporate
alemtuzumab in the hyper-CVAD induction program for
patients with relapsed or refractory T-cell hematopoietic
malignancies. The CALGB is testing alemtuzumab
in the setting of postremission therapy for those patients
whose lymphoblasts were CD52-positive at diagnosis
[8]. In another randomized CALGB study, anti-
B4bR (anti-CD19 monoclonal antibody conjugated to
blocked ricin) during minimal residual disease showed
little additional clinical evidence [21].
Imatinib is increasingly explored in Philadelphia
chromosome-positive ALL. Thomas et al. pioneered
imatinib-chemotherapy combinations in previously untreated
patients [22]. Imatinib is added at a dose of 400
mg/day for the first 14 days of each of the eight induction/consolidation
courses of the hyper-CVAD regimen
which is followed by 1 year of maintenance with imatinib
at 600 mg orally daily. Of 15 patients who have been
treated with active disease (11 with de novo ALL and
four who were primary failures following nonimatinib
containing induction therapy), all achieved CR. Ten patients
underwent allogeneic stem cell transplantation
within a median of 3.5 months. Among 10 patients
who did not undergo transplant, five remain in continuous
CR for a median of 20 months. The German ALL
study group (GMALL) is conducting a randomized
phase II study of induction therapy with imatinib versus
standard induction chemotherapy in patients > 55 years
with Philadelphia chromosome-positive ALL [23]. In a
preliminary update, all patients treated with imatinib
induction achieved CR whereas two patients assigned
to chemotherapy induction failed and were crossed over
to the imatinib arm. It is hoped that accumulating experience
resulting from these and other regimens will
establish the role of in kinase situs in Philadelphia
chromosome-positive ALL and set a new standard of
care for these patients.
A number of other novel agents are investigated in
relapsed in refractory disease states and include new
nucleoside analogs (clofarabine, nelarabine), liposomal
agents (liposomal vincristine), or hypomethylating
agents (decitabine).
9.4 Conclusion
ALL is a heterogeneous disease where ALL subsets are
characterized by distinct clinical, biological, and thus
prognostic features. In addition to developing novel
therapies, adapting these therapies according to the risk
profile of individual patients has become a main focus
in ALL treatment in recent years [24]. Traditional risk
factors such as age, white blood cell count, time to response,
or cytogenetic abnormalities have shown to influence
outcome. More recently, assessment of minimal
residual disease has emerged as a tool to gauge individual
response following achievement of a complete remission.
The GMALL study group is prospectively monitoring
minimal residual disease of patients during induction
and early consolidation and has started to stratify
patients according to residual disease levels at day
71 as low-, high-, or intermediate risk for relapse. The
goal of these further refinements is clear: (i) identification
of patients who should be transplanted in first CR;
(ii) adjustments of intensity during consolidation; and
(iii) possible modifications in the intensity and duration
of maintenance therapy.
ALL therapy in adults has stepped out of the
shadows from its pediatric role model. Even though
battling the odds seems more cumbersome in adults,
important progress has been made to combine an increasing
understanding of the biology of adult ALL with
the development of novel therapies and the accumulating
experience of the clinical behavior of ALL during
therapy. ALL therapy has become a complex endeavor
and will be even more so in the future. The following
articles in this section will provide a far more in-depth
description of this progress and create an outlook at
state-of-the art therapy in this intriguing disease.
References
1. Kantarjian HM, O’Brien S, Smith TL, et al. (2000) Results of treatment
with hyper-CVAD, a dose-intensive regimen, in adult acute
lymphocytic leukemia. J Clin Oncol 18:547–561
2. Larson RA, Dodge RK, Burns CP, et al. (1995) A five-drug remission
induction regimen with intensive consolidation for adults with
acute lymphoblastic leukemia: Cancer and Leukemia Group B
Study 8811. Blood 85:2025–2037
3. Durrant IJ, Richards, SM, Prentice HG, et al. (2000) The Medical Research
Council trials in adult acute lymphocytic leukemia. Hem
Onc Clin North Am 14:1327–1352