Purpose We examined post relapse outcomes for children initially treated on CCG-1952 and compared stem cell transplant (SCT) with chemotherapy (CT) as salvage treatment in second remission (CR2).
Methods Between 5-96 and 1-00, 2176 eligible patients with standard risk (SR)-ALL (WBC ≤ 50,000/mcl; age ≥ 1, ≤ 10 years) were enrolled on CCG-1952, 321 of whom experienced a relapse. We evaluated outcomes after bone marrow (BM)  extramedullary (EM) relapse and isolated EM (iEM: CNS, testicular, or ocular) relapse using Kaplan-Meier life table analysis and compared event-free survival (EFS) and overall survival (OS) after SCT with outcomes after CT using the log rank test.
Results Among the relapses, 196 are BM ± EM relapses (61%) and 125 are iEM relapses (39%). The median (range) from first remission to BM relapse, iCNS relapse, and itesticular relapse is 34.1 (2 to 79) month (mo.), 19.6 (1 to 70) mo., and 39.2 (4 to 74) mo., respectively. The 3-year EFS and OS after relapse for all patients are 41% and 53%. Three-year EFS and OS after BM ± EM relapse are 32% and 40%, and after iEM relapse, are 55% and 71%. Patients with early BM relapse (CR1 ≤ 36 months) or early iEM relapse (CR1 ≤ 18 months) are 2.3 times (p=0.002) and 2.8 times (p=0.01) more likely to suffer a subsequent adverse event than patients with later relapse by Cox regression analysis after adjustment for age, pre-relapse treatment, day 7/14 BM status, and type of treatment in CR2. The 3-year OS for early and late relapses are 31% vs 59% (p=0.001) for BM relapse and 50% vs 87% (p=0.01) for iEM relapse. We compared 73 SCT and 215 CT patients, excluding 33 patients with adverse events prior to the median time to SCT (130 days, range 56 to 1148 days). The cohorts are similar with respect to age (p=0.57), duration of CR1 (p=0.96), and initial Day 14 BM status (p=0.69). Thus far, no difference between SCT and CT is apparent among all BM relapse patients (OS, p=0.45; EFS p=0.70), among patients with early BM relapse (OS, p=0.95; EFS p=0.66), or among patients with iEM relapse (OS, p=0.44, EFS, p=0.96). Among patients with later BM relapse, a trend favors CT (OS, p=0.08, EFS, p= 0.14).
Conclusion Duration of CR1 remains the most significant predictor of outcome after either BM or iEM relapse. Prognosis after early BM relapse remains poor and is not improved with SCT in this SR-ALL cohort.
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