Isolated late testicular relapse of B-cell acute lymphoblastic leukemia treated with intensive systemic chemotherapy and response-based testicular radiation: A Children's Oncology Group study

Abstract

Background: The incidence of isolated testicular relapse (ITR) of acute lymphoblastic leukemia (ALL) has decreased with contemporary treatment strategies, but outcomes are suboptimal with a 58% 5-year overall survival (OS). This study aimed to improve outcome in patients with ITR of B-cell ALL (B-ALL) occurring after 18 months of first clinical remission using intensive systemic chemotherapy and to decrease long-term sequelae by limiting use of testicular radiation.

Procedure: Forty patients in first ITR of B-ALL were enrolled. Induction (dexamethasone, vincristine, daunorubicin, and intrathecal triple therapy) was preceded by one dose of high-dose methotrexate (MTX, 5 g/m² ). Following induction, 25 of 26 patients who had persistent testicular enlargement underwent testicular biopsy. Eleven had biopsy-proven disease and received bilateral testicular radiation (24 Gy), whereas twenty-nine did not.

Results: Overall 5-year event-free survival (EFS)/OS was 65.0 ± 8.8%/73.1 ± 8.3%, with 5-year EFS 62.1 ± 11.0% vs. 72.7 ± 14.4% for patients who did not receive radiation therapy (XRT) (n = 29) compared with those who did (n = 11), respectively (P = 0.64). There were six second bone marrow relapses and six second ITRs. The proportion of second relapses was similar in the patients that received testicular radiation and those who did not. However, the 5-year OS was similar for patients who did not receive XRT (72.6 ± 10.2%) compared with those who did (72.7 ± 14.4%) (P = 0.85).

Conclusions: A 5-year OS rate of 73.1 ± 8.3% was obtained in children with first ITR of B-ALL occurring after 18 months of CR1 (length of first clinical remission) using intensive chemotherapy and limiting testicular radiation.

FIGURE 1

CONSORT Diagram: Patient treatment and outcomes. Pathway followed by all patients enrolled on AALL02P2. Patients were excluded from the final analysis for ITR patients based on ineligibility (2), isolated CNS relapse (124), and T-ALL phenotype (32). The remainder 40 B-ALL ITR patients had an initial assessment of response at the end of induction therapy. Testicular biopsy positive patients received testicular radiation during consolidation therapy, whereas those with a negative biopsy did not

FIGURE 2

Event-free survival (EFS) and overall survival (OS) of ITR patients with B-ALL enrolled on the Children's Oncology Group (COG) AALL02P2 and stratified by testicular radiation. Five-year EFS for B-ALL patients with ITR was 65.0 ± 8.8% (Figure 2A), whereas 5-year OS was 73.1 ± 8.3% (Figure 2B). Five-year EFS was 72.7 ± 14.4% for those who receive testicular radiation and 60.7 ± 11.5% for patients who did not (Figure 2C). In comparison, 5-year OS for patients with ITR treated with testicular radiation was 72.7 ± 14.4% compared to 71.4 ± 10.6% for patients who did not receive testicular radiation (Figure 2D)