Treatment of occult or late overt testicular relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study.
Author(s): Wofford MM, Smith SD, Shuster JJ, Johnson W, Buchanan GR, Wharam MD, Ritchey AK, Rosen D, Haggard ME, Golembe BL
Affiliation(s): Bowman-Gray School of Medicine, Winston Salem, NC.
Publication date & source: 1992-04, J Clin Oncol., 10(4):624-30.
Publication type: Clinical Trial; Randomized Controlled Trial
PURPOSE: The Pediatric Oncology Group (POG) designed a randomized two-arm protocol (8304) to improve the survival of children with acute lymphoblastic leukemia (ALL) who experience an isolated testicular relapse and to evaluate the efficacy of teniposide (VM-26) and doxorubicin as intensification agents during second remission. The outcome and toxicity observed in 80 patients with isolated testicular leukemia treated on POG 8304 are presented. PATIENTS AND METHODS: The following are common features of POG 8304: (1) remission reinduction therapy with vincristine, prednisone, and doxorubicin; (2) bilateral testicular irradiation (2,600 cGy) during reinduction therapy; (3) CNS prophylaxis with intrathecal hydrocortisone, methotrexate (MTX), and cytarabine (Ara-C); and (4) continuation therapy (for 80 weeks) with alternating 6-week cycles of oral mercaptopurine (6-MP)/MTX and intravenous vincristine and cyclophosphamide. Treatment differences consisted of pulses (administered every 7 weeks) of either prednisone and doxorubicin (arm 1) or VM-26 and Ara-C (arm 2) during continuation therapy and a 4-week late intensification phase with either vincristine, prednisone, and doxorubicin (arm 1) or VM-26 and Ara-C (arm 2). RESULTS: Fifty-five boys with ALL had isolated microscopic testicular leukemia detected by an elective biopsy at completion of initial treatment, and 25 had a late (greater than or equal to 6 months off-therapy) isolated overt testicular relapse. All patients with overt testicular leukemia attained a second clinical remission, and no patient with microscopic testicular leukemia progressed during reinduction. Of 42 patients on arm 1, 11 have relapsed compared with 18 of 38 patients on arm 2 (log-rank analysis, P = .22), indicating no significant difference between an anthracycline and an epipodophyllotoxin-Ara-C combination in the treatment of testicular leukemia. The overall 4-year event-free survival (EFS) among boys with occult testicular relapse was 53% +/- 8%. Age greater than 10 years at initial diagnosis, a WBC count greater than 50,000/microL at diagnosis, and black race were associated with a worse outcome. The 4-year EFS for boys with a late overt testicular relapse was 84% +/- 10%, and these patients fared significantly better than patients with occult disease (P = .007). CONCLUSION: The treatment approach reported here can secure a prolonged second remission in many patients with occult or late overt testicular leukemia.