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.

Outcomes after late bone marrow and very early central nervous system relapse of childhood B-acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433

“…However, more recent reports suggest similar HCT outcomes regardless of donor type [20] [23] . COG AALL0433 (NCT# 00381680) for intermediate-risk first relapse of B-ALL was instituted to evaluate the efficacy of a hybrid platform, combining elements from prior COG studies for both bone marrow and IEM relapse [24] [25] [26]. Eligible patients overlap considerably with the S2 group from BFM relapse trials [15].…”

“…This report details results from AALL0433. Treatment AALL0433 utilized chemotherapy beginning with three intensive blocks from COG AALL01P2 [24], followed by intensification, reinduction, and maintenance from COG 9412/AALL02P2 [25] [26] (Figure 1, Supplemental Table S1). The duration of therapy was 2 years.…”

FERTILITY PRESERVATION: Testicular transplantation for fertility preservation: clinical potential and current challenges

“…For acute lymphoblastic leukaemia (ALL), focal leukaemic infiltrates have been reported in 7/33 (21%) prepubertal boys prior to treatment (Kim et al 1986). Furthermore, late relapse may occur >10 years after treatment (Barredo et al 2018).…”

“…However, whether this approach can be used to detect contamination in tissues containing very few malignant cells or whether this can also be applied to human tissue is unknown. Furthermore, the duration of xenografting used for such studies may not be sufficient to determine the potential for late relapse from leukaemia as has been described in humans many years after completion of treatment (Barredo et al 2018).…”

Is testicular irradiation necessary for patients with acute lymphoblastic leukemia and testicular relapse?

“…The Barredo study would have been more informative had it been possible to compare prognostic indicators between the irradiated and the nonirradiated cohorts. The presence of minimal residual disease (MRD) at diagnosis of testicular relapse was correlated with a poor outcome for the entire cohort; two relapses (both hematologic) occurred in two of the three patients with a positive MRD finding (0.01% and 0.1%) as compared to only seven relapses (five hematologic and two testicular) in the remaining 26 patients without detectable MRD . Although MRD was not predictive of subsequent testicular relapse, regardless of treatment with or without testicular radiation, it is unclear whether MRD results were balanced between the two cohorts of patients.…”