Long-term results of Total Therapy studies 11, 12 and 13A for childhood acute lymphoblastic leukemia at St Jude Children's Research Hospital

Abstract

We present the long-term results of three consecutive clinical trials (Total Therapy studies 11, 12 and 13A) conducted for children with newly diagnosed acute lymphoblastic leukemia (ALL) between 1984 and 1994. In study 11 (1984)(1985)(1986)(1987)(1988), the overall event-free survival rates (؎1 s.e.) were 71.8 ؎ 2.4% and 69.3 ؎ 2.4%, and the cumulative risks of isolated central nervous system (CNS) relapse 5.6 ؎ 1.2% and 5.9 ؎ 1.3%, at 5 and 10 years, respectively. In study 12 (1988-1991), event-free survival rates were 67.6 ؎ 3.4% and 61.5؎ 9.0%, and isolated CNS relapse rates were 10.4 ؎ 2.3% and 10.4 ؎ 2.3%, respectively. Early intensive intrathecal therapy in study 13A (1991-1994) has yielded a very low 5-year isolated CNS relapse rate of 1.2 ؎ 0.9%, boosting the 5-year event-free survival rate to 76.9 ؎ 3.3%. Factors consistently associated with an adverse prognosis included male sex, infant or adolescent age group, leukocyte count Ͼ100 ؋ 10 9 /l, nonhyperdiploidy karyotype and poor early response to treatment. Risk classification based on age and leukocyte count had prognostic significance in B-lineage but not T-lineage ALL. Early therapeutic interventions or modifications for patients with specific genetic abnormalities or persistent minimal residual leukemia may further improve long-term results. Leukemia (2000) 14, 2286-2294.

Implementation of an intensive risk‐stratified treatment protocol for children and adolescents with acute lymphoblastic leukemia in Lebanon

“…The overall 5-year EFS of 78.7% for our patients was comparable to the 5-year EFS of 75% for patients treated on the CCG-1800 series [6], 76.9% in the TOTAL therapy study 13A at St. Jude Children's Research Hospital [28], and 78% in the BFM 90 [29]. The percentage of patients who relapsed in our study (7.2%) compares favorably with that in many resource-poor countries (17.5%-41.1%) [20,21,30,31].…”

International childhood Acute Lymphoblastic Leukemia workshop: Sausalito, CA, 30 November–1 December 2000

“…The intent was to identify effective treatment for certain well-defined subsets of patients. This unprecedented effort resulted in 12 informative articles published together in the December 2000 issue of Leukemia, [5][6][7][8][9][10][11][12][13][14][15][16] providing valuable clues to advance the cure rate in future trials.…”

Low-dose oral etoposide-based induction regimen for children with acute lymphoblastic leukemia in first bone marrow relapse

“…In all, 39 patients were previously treated on St Jude Total Therapy studies XI, XII, XIIIA, and XIIIB. 1,20 Six patients including three with an initial diagnosis of non-Hodgkin's lymphoma received frontline therapies other than those used in these Total Therapy protocols. 21,22 All patients but one had received prior treatment with epipodophyllotoxins.…”

“…1,2 Nevertheless, disease in approximately 20-25% of patients relapses or is refractory to frontline therapies. 3 The results of salvage treatments for relapsed ALL, especially for early hematologic relapse, have been disappointing.…”