Vacunas

The

n e w e ng l a n d j o u r na l

of

m e dic i n e

review article

drug therapy

Treatment of Acute Lymphoblastic Leukemia
Ching-Hon Pui, M.D., and William E. Evans, Pharm.D.
From the Departments of Hematology and Oncology (C.-H.P.), Pharmaceutical Sciences (W.E.E.), and Pathology (C.-H.P.), St. Jude Children’s Research Hospital; and the Colleges of Medicine (C.-H.P., W.E.E.)and Pharmacy (W.E.E.), University of Tennessee Health Science Center — both in Memphis. Address reprint requests to Dr. Pui at St. Jude Children’s Research Hospital, 332 N. Lauderdale St., Memphis, TN 38105-2794, or at ching-hon. pui@stjude.org.

N Engl J Med 2006;354:166-78.
Copyright © 2006 Massachusetts Medical Society.

lmost 4000 cases of acute lymphoblastic leukemia (ALL) are diagnosedannually in the United States, approximately two thirds of which are in children and adolescents, making ALL the most common cancer in these age groups.1 Optimal use of the same antileukemic agents that were developed from the 1950s through the 1980s, together with a stringent application of prognostic factors for risk-directed therapy in clinical trials, has resulted in a steady improvement intreatment outcome.1 In the 1990s, the five-year event-free survival rates for childhood ALL generally ranged from 70 to 83 percent in developed countries (Table 1),2-11 with an overall cure rate of approximately 80 percent.1 Emerging results suggest that a cure rate of nearly 90 percent will be attained in the near future12 (Fig. 1). Unfortunately, the experience with adult ALL has been far lessrewarding: reported cure rates seldom exceed 40 percent (Table 2), despite the use of hematopoietic stem-cell transplantation in many cases.13-20 The poor outcome in adult ALL has been variously attributed to an increased frequency of high-risk leukemia with greater drug resistance, poorer tolerance of and compliance with treatment, reluctance to accept certain temporary toxic effects, and lesseffective treatment regimens, as compared with childhood ALL. In this review, we consider recent advances in the treatment of ALL, emphasizing issues that must be addressed if treatment outcome is to improve further.

A

R isk A s se s smen t
A stringent assessment of the risk of relapse for subgroups of patients is critical in selecting therapy that will avoid excessive toxicity but maintain ahigh cure rate. Risk classification has been based mainly on readily apparent clinical features of patients and characteristics of leukemia cells.1 Certain host factors are now recognized to exert a critical influence on treatment efficacy and toxicity.21,22 In some patients, for example, treatment failure results from inadequate drug dosing rather than from an intrinsic drug resistance of theleukemia cells.1,23 Although most pediatric study groups classify patients into categories of standard, high (i.e., intermediate or average), or very high risk, the Children’s Oncology Group has proposed a four-category system that recognizes patients with a very low probability of relapse.24 Adults are generally divided into only standard-risk and high-risk groups.

Fac t or s Pr edic t ing Cl inica l Ou t c ome
treatment regimen

Improved treatment has abolished the prognostic strength of many clinical and biologic variables that previously were related to outcome. For example, T-cell ALL or mature B-cell ALL in children, once associated with a very poor prognosis, has a cure rate of 75 to 80 percent with contemporary treatments.25,26 Similarly, although

166

n engl j med 354;2www.nejm.org

january 12, 2006

Downloaded from www.nejm.org by ROBIN WINTER on March 25, 2007 . Copyright © 2006 Massachusetts Medical Society. All rights reserved.

drug ther apy

black children still have poor outcomes in national studies, they have the same high cure rates as white children when given equal access to effective treatment in trials at single institutions.27 The...