PURPOSE Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored. PATIENTS AND METHODS We prospectively registered AAP (n = 168) during treatment of 2,448 consecutive ALL patients aged 1.0-45.9 years diagnosed from July 2008 to October 2018 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. RESULTS Compared with patients aged 1.0-9.9 years, adjusted AAP hazard ratios (HRa) were associated with higher age with almost identical HRa (1.6; 95% CI, 1.1 to 2.3; P = .02) for adolescents (10.0-17.9 years) and adults (18.0-45.9 years). The day 280 cumulative incidences of AAP were 7.0% for children (1.0-9.9 years: 95% CI, 5.4 to 8.6), 10.1% for adolescents (10.0 to 17.9 years: 95% CI, 7.0 to 13.3), and 11.0% for adults (18.0-45.9 years: 95% CI, 7.1 to 14.9; P = .03). Adolescents had increased odds of both acute (odds ratio [OR], 5.2; 95% CI, 2.1 to 13.2; P = .0005) and persisting complications (OR, 6.7; 95% CI, 2.4 to 18.4; P = .0002) compared with children (1.0-9.9 years), whereas adults had increased odds of only persisting complications (OR, 4.1; 95% CI, 1.4 to 11.8; P = .01). Fifteen of 34 asparaginase-rechallenged patients developed a second AAP. Asparaginase was truncated in 17/21 patients with AAP who subsequently developed leukemic relapse, but neither AAP nor the asparaginase truncation was associated with increased risk of relapse. CONCLUSION Older children and adults had similar AAP risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse.

中文翻译：

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急性淋巴细胞白血病中的天冬酰胺酶相关胰腺炎：NOPHO ALL2008 治疗 1-45 岁患者的结果

目的 天冬酰胺酶相关性胰腺炎 (AAP) 在急性淋巴细胞白血病 (ALL) 患者中很常见，但尚未探讨与首次 AAP 和天冬酰胺酶再次暴露相关的年龄组之间的风险差异。患者和方法 我们在 2,448 名年龄在 1.0-45.9 岁的连续 ALL 患者的治疗期间前瞻性登记了 AAP（n = 168），这些患者从 2008 年 7 月至 2018 年 10 月诊断并根据北欧儿童血液学和肿瘤学会 (NOPHO) ALL2008 协议进行治疗。结果 与 1.0-9.9 岁的患者相比，调整后的 AAP 风险比 (HRa) 与更高的年龄相关，青少年（10.0-17.9 岁）的 HRa 几乎相同（1.6；95% CI，1.1 至 2.3；P = .02）和成人（18.0-45.9 岁）。儿童（1.0-9.9 岁：95% CI，5. 4 至 8.6），青少年为 10.1%（10.0 至 17.9 岁：95% CI，7.0 至 13.3），成人为 11.0%（18.0-45.9 岁：95% CI，7.1 至 14.9；P = .03）。青少年发生急性（比值比 [OR]，5.2；95% CI，2.1 至 13.2；P = .0005）和持续并发症（OR，6.7；95% CI，2.4 至 18.4；P = .0002）的几率增加与儿童（1.0-9.9 岁）相比，成人仅出现持续并发症的几率增加（OR，4.1；95% CI，1.4 至 11.8；P = .01）。34 名接受天冬酰胺酶治疗的患者中有 15 名发生了第二次 AAP。17/21 的 AAP 患者随后发生白血病复发，天冬酰胺酶被截断，但 AAP 和天冬酰胺酶截断均与复发风险增加无关。结论 年龄较大的儿童和成人有相似的 AAP 风险，而发病率在青少年中最为明显。