Journal of Clinical Oncology, Vol 10, 624-630, Copyright © 1992 by American Society of Clinical Oncology
Treatment of occult or late overt testicular relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study
MM Wofford, SD Smith, JJ Shuster, W Johnson, GR Buchanan, MD Wharam, AK Ritchey, D Rosen, ME Haggard and BL Golembe
Bowman-Gray School of Medicine, Winston Salem, NC.
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.
