Bilateral Involvement Is an Independent Risk Factor in Testicular Relapse of Childhood ALL: Results of the Trials ALL-REZ BFM 83 - 2002

Abstract

▪Introduction:In childhood acute lymphoblastic leukemia (ALL) about 15-20% of patients suffer from relapse after frontline therapy. The testes are the second most frequent site of extramedullary relapse. Up to now there are no data on the impact of the extent of testicular relapse on prognosis.Patients and Methods:We retrospectively analyzed outcome of children with testis relapse of ALL who were treated according to ALL-REZ BFM trials from March 1983 until December 2013. Only patients with first relapse were included in the analysis. From a total of 1603 boys registered within the ALL-REZ trials since 1983, testicular involvement was identified in 302 patients. Local therapy consisted of orchiectomy (or irradiation at 24 Gray) of clinically involved testes. Clinically not involved testes were irradiated at 15 or 18 Gray in case of histologically proven leukemic infiltration. Most patients received intensive multi-drug chemotherapy followed by conventional maintenance therapy.Results:Extent and time point of relapse did not significantly differ between isolated testicular (n=135) and combined BM and testicular relapse (n=167). Isolated testicular relapse was associated with improved 5 year-event free survival (pEFS) compared with combined relapse (0.70±0.04 vs. 0.54±0.04, p=0.005). Bilateral testicular involvement accounted for a worse pEFS than unilateral involvement (0.48±0.05 vs. 0.71±0.04, p<0.0001). This was particularly evident in patients with isolated testicular relapse (bilateral (0.53±0.08) vs. unilateral relapse (0.79±0.05), p<0.0001), but not in combined relapse (bilateral (0.45±0.06) vs. unilateral relapse (0.62±0.06), p=0.11). Only in patients with very early/early isolated testicular relapse bilateral testicular involvement was associated with poor outcome (0.40±0.09 vs. 0.68±0.08, p=0.015), whereas no significant differences were detected in the late relapse group (0.79±0.11 vs 0.86±0.05, p=0.11). Multivariate analysis identified time point of relapse, extent of testicular relapse and combined relapse as independent risk factors in testicular ALL relapse. Subsequent local relapse was rare, ninty-eight patients (32.5%) suffered a subsequent, mostly BM relapse.Conclusion:Isolated testicular relapse is associated with improved outcome compared to combined BM/testicular relapse. Bilateral testicular involvement is an independent risk factor for relapse, particularly prognosis of patients with (very) early isolated bilateral testicular relapse was poor. As local in contrast to systemic subsequent relapse was rare, this group of patients might benefit from intensification of chemotherapy including allogeneic stem cell transplantation. DisclosuresNo relevant conflicts of interest to declare.