Retrospective Survey of Children Treated for Relapsed Acute Lymphoblastic Leukemia (Complete Remission (CR) Rates): A Report from the Therapeutic Advances in Childhood Leukemia (TACL) Consortium.

Abstract

Introduction: Event-free survival (EFS) for children with ALL is approximately 80%. Despite substantial success in achieving second and subsequent remissions, survival of patients with relapsed ALL (rALL) remains dismal. We propose that progress depends on identification of novel drug combinations with more activity in rALL than those commonly employed. The literature suggests a 40% CR rate for second and subsequent relapse (Br. J Haematol 2005; 131:579). However, CR rates depend on the number of prior therapeutic attempts and duration of any prior response, complicating identification of promising regimens. Limited patient numbers and a large number of potential candidate regimens discourage randomized trials. We surveyed local experience with rALL to establish a robust benchmark for evaluation of novel drug combinations.Methods: The TACL Consortium (www.tacl.us) was formed to develop novel drug combinations for patients with rALL. We initiated a review of all patients with rALL treated between 1995 and 2004 at eight TACL institutions. Detailed data on therapy, response, and duration of response were collected on all patients.Results: Of 313 rALL patients, 62% were males, 27% were older than 10 years at diagnosis, 26% had initial white blood counts (WBC) at diagnosis >=50,000/uL, and 46% were high-risk by NCI risk criteria. Re-induction attempts ranged between 1 and 9 and most commonly employed combinations of traditional ALL agents. Limiting analyses to patients with marrow involvement, we obtained 86% CR's for 1st relapse (95% confidence interval 80%–90%), 44% for second relapse (35%–53%), and 30% for third relapse (19%–43%). CR rates declined with the number of prior treatment attempts (see Table, p<0.001). With first relapse, the CR rate trended lower in older patients (<10 y.o., 89%; ≥ 10 y.o., 78%; p=.056). With second relapse, CR rates increased with a longer duration of the prior remission (p<0.005), but this was not true for first relapse. (p=0.33).Conclusion: Our data support a 40% baseline CR rate for 2nd and subsequent relapse ALL and provide a useful benchmark for comparison with new therapies.CR Rates by Treatment Attempt and Duration of Any Prior RemissionCR Rates (percent)CR status/ duration of previous CR2nd Attempt3rd Attempt4th AttemptCR not achieved with prior attempt8/8 (100)3/14 (21)10/35 (29)CR < 18 months41/52 (79)26/ 69 (38)5/ 22 (23)CR 18–36 months59/ 66 (89)14/ 23 (61)1/ 1(100)CR ≥ 36 months61/ 68 (90)7/ 10 (70)1/ 1(100)CR unknown16/22 (73)2/2 (100)1/ 1(100)Totals185/216 (86)52/118 (44)18/ 60 (30)