Background

Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with cytarabine and methotrexate (hyper-CVAD) is a commonly used regimen in adults with acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). Adult patients fit for pediatric-inspired protocols have an excellent outcome with chemotherapy alone. However, it is unclear whether patients receiving hyper-CVAD should undergo allogeneic hematopoietic cell transplantation (HCT) as postremission therapy. Our aim was to examine the role of HCT at first complete remission (CR1) in adult ALL/LBL after hyper-CVAD.

Patients and Methods

Adult patients with newly diagnosed ALL/LBL receiving frontline hyper-CVAD from 2008 to 2018 were identified and records retrospectively extracted.

Results

A total of 85 patients were identified and included for further analysis. The median (range) age was 23 (14-68) years, and 56 (66%) were male. A total of 24 (28%) had adverse cytogenetics, and 48 (56%) had at least one risk factor. All patients received hyper-CVAD as induction; induction failure was seen in 10 (12%). A total of 38 patients continued the hyper-CVAD course, while the remaining 47 received HCT in CR1. Three-year event-free survival (EFS) and overall survival for the entire cohort were 51.4% and 61.6%, respectively. Median follow-up of alive patients was 39.9 (3.8-123.8) months. At multivariable analysis for EFS, induction failure was associated with worse outcome (hazard ratio [HR], 4.8; 95% confidence interval [CI] 1.7-13.7; P = .003), whereas HCT in CR1 improved outcome (HR, 0.42; 95% CI 0.18-0.97; P = .044). Furthermore, HCT in CR1 was the only prognostic factor for overall survival (HR, 0.3; 95% CI 0.11-0.85; P = .023).

Conclusion

HCT at CR1 resulted in a favorable EFS and overall survival in ALL/LBL patients after hyper-CVAD frontline therapy. Given that hyper-CVAD is a widely used protocol for adult patients, further examination of this observation is warranted.

中文翻译：

---

同种异体 HCT 作为前线 Hyper-CVAD 后适合移植的成人淋巴细胞白血病/淋巴瘤的缓解后治疗的作用。

背景

超分割环磷酰胺、长春新碱、多柔比星和地塞米松与阿糖胞苷和甲氨蝶呤交替（hyper-CVAD）是成人急性淋巴细胞白血病（ALL）/淋巴细胞淋巴瘤（LBL）的常用方案。适合儿科方案的成年患者仅接受化疗即可获得出色的结果。然而，目前尚不清楚接受 hyper-CVAD 的患者是否应接受异基因造血细胞移植 (HCT) 作为缓解后治疗。我们的目的是检查 HCT 在首次完全缓解 (CR1) 时在成人 ALL/LBL 中 hyper-CVAD 后的作用。

患者和方法

对 2008 年至 2018 年接受一线 hyper-CVAD 的新诊断 ALL/LBL 成人患者进行识别并回顾性提取记录。

结果

共有 85 名患者被确定并纳入进一步分析。中位（范围）年龄为 23（14-68）岁，56 人（66%）为男性。共有 24 人 (28%) 有不良细胞遗传学，48 人 (56%) 有至少一种危险因素。所有患者均接受 hyper-CVAD 作为诱导；在 10 个 (12%) 中观察到感应失败。共有 38 名患者继续进行 hyper-CVAD 疗程，而其余 47 名患者在 CR1 中接受了 HCT。整个队列的三年无事件生存率 (EFS) 和总生存率分别为 51.4% 和 61.6%。存活患者的中位随访时间为 39.9 (3.8-123.8) 个月。在 EFS 的多变量分析中，诱导失败与更差的结果相关（风险比 [HR]，4.8；95% 置信区间 [CI] 1.7-13.7；P = .003)，而 CR1 中的 HCT 改善了结果（HR，0.42；95% CI 0.18-0.97；P  = .044）。此外，CR1 中的 HCT 是总生存期的唯一预后因素（HR，0.3；95% CI 0.11-0.85；P  = .023 ）。

结论

在超 CVAD 一线治疗后，CR1 的 HCT 导致 ALL/LBL 患者良好的 EFS 和总生存期。鉴于 hyper-CVAD 是一种广泛用于成人患者的方案，因此有必要进一步检查这一观察结果。