| Abstract: |
Therapy for childhood lymphoblastic leukemia has evolved during the past three decades, but key questions about what are the least toxic, most effective forms of treatment remain unanswered because of the lack of comprehensive follow-up information. To assess long-term outcome in the series of clinical trials conducted at St. Jude Hospital, we compared the results of treatment typical of four eras: exploratory combination chemotherapy (era 1, 1962 to 1966; 91 patients), regimens for the control of meningeal leukemia (era 2, 1967 to 1979; 825 patients), limited intensification of therapy (era 3, 1979 to 1983; 428 patients), and extended intensification of therapy (era 4, 1984 to 1988; 358 patients). (“Intensification” refers to strategies of systemic chemotherapy that are more aggressive than conventional ones.) The major end points were survival and event-free survival; we also calculated the relative risk of treatment failure and the rate of relapse or death after treatment ended (post-treatment failure rate). The probability of event-free survival improved significantly in each successive era (P<0.001 by the log-rank test), reaching 71 percent in era 4. There was a decrease of approximately 50 percent in the risk of treatment failure from one era to the next in each subgroup of patients defined according to different combinations of the leukocyte count, race, age, and sex. Leukemia appeared to be eradicated in patients who remained in complete remission for three years or more after treatment in era 4. The incidence of death due to nonleukemic causes remained 4 to 6 percent despite the trend toward more intensive treatment. An estimated 765 patients (45 percent) are long-term survivors; most of them (80 percent) have no health problems related to leukemia or its treatment. The development and successful application of preventive therapy for meningeal leukemia, followed by the intensification of systemic chemotherapy, has progressively improved the rate of cure of childhood lymphoblastic leukemia, with relatively few adverse sequelae., When treated with effective multiagent chemotherapy, about two thirds of children with newly diagnosed acute lymphoblastic leukemia survive for long periods of time1–4. Much of this success can be credited to more intensive early treatment, especially of patients at higher risk of relapse. Although the benefits of intensive therapy are clear, its appropriateness for all groups of patients remains in question5–7. Moreover, the inevitable lag between the planning of treatment for acute lymphoblastic leukemia and the recognition of severe delayed toxicity has exacted a high toll in morbidity and mortality due to potentially avoidable side effects... © 1993, Massachusetts Medical Society. All rights reserved. |
| Keywords: |
adolescent; cancer survival; child; treatment outcome; child, preschool; treatment failure; major clinical study; cancer recurrence; cancer radiotherapy; methotrexate; follow-up studies; bone marrow suppression; antineoplastic combined chemotherapy protocols; antineoplastic activity; cancer mortality; acute lymphoblastic leukemia; childhood cancer; cancer regression; infant; leukocyte count; second cancer; cotrimoxazole; sulfamethoxazole; trimethoprim; epipodophyllotoxin; drug mixture; leukemia, lymphocytic, acute; prognosis; human; male; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; brain leukemia
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