采用改良的风险适应方案治疗朗格汉斯细胞组织细胞增生症-来自印度一家三级癌症研究所的经验。

Treatment of Langerhans cell histiocytosis with a modified risk-adapted protocol-experience from a tertiary cancer institute in India.

机构信息

Pediatric Hematolymphoid Disease Management Group, Department of Medical Oncology, Tata Memorial Center, Mumbai, India.

出版信息

Pediatr Blood Cancer. 2018 Aug;65(8):e27028. doi: 10.1002/pbc.27028. Epub 2018 Mar 7.

DOI:10.1002/pbc.27028

PMID:29512864

Abstract

BACKGROUND

Involvement of risk-organs (RO+) in Langerhans cell histiocytosis (LCH) and inadequate early response identifies patients at high risk for relapse and mortality requiring intensive salvage therapy including stem cell transplant, adding cost and toxicity. To mitigate this, we used a standard induction, augmented with metronomic etoposide, and prolonged maintenance-similarly augmented for RO+, and retrospectively analyzed its impact.

PROCEDURE

LCH patients from 2009 through 2014 were included. Patients received standard vinblastine and prednisolone therapy weekly till week 25 for RO+. Single site (SS) and multisystem (MS) without risk organ involvement (RO-) received 3-weekly pulses from week 13 till week 25. Maintenance was 3-weekly vinblastine and 5-day prednisolone pulses, daily 6-mercaptopurine (60 mg/m ) and weekly methotrexate (15 mg/m ) for 18 and 9 months for RO+ and MSRO-, respectively. RO+ also received oral etoposide (50 mg/m ) for 21 of every 28-day cycle for the first year.

RESULTS

Fifty consecutive patients were analyzed. Median age was 36 months (4-189 months). SS, MSRO-, and RO+ were 29 (58%), 12 (24%), and nine (18%), respectively. Four were lost to follow-up and excluded from further evaluation. On response evaluation at week 6, 24 (52%) had no active disease (NAD), 17 (37%) had AD-better (where AD is active disease), and one (2%) had AD-worse. In RO+, eight (66.6%) had AD-better and three (25%) had NAD. Forty-five patients had NAD by week 12. Three patients relapsed. With median follow-up of 39 months (8-84), 5-year event free survival was 85.6% (RO- and SS), and 100% for RO+. One patient's death in remission from unrelated causes resulted in overall survival of 97%.

CONCLUSIONS

RO+LCH receiving oral etoposide augmented induction and maintenance had early and durable responses. Prolonging maintenance lowered reactivation rates in RO+ and RO-LCH, resulting in excellent survival.

摘要

背景

朗格汉斯细胞组织细胞增生症（LCH）累及风险器官（RO+）和早期反应不足会使患者面临高复发和死亡风险，需要强化挽救性治疗，包括干细胞移植，这会增加成本和毒性。为了降低这种风险，我们使用标准诱导方案，加用节拍式依托泊苷，并延长维持治疗-同样针对 RO+进行强化，然后回顾性分析其影响。

方法

纳入 2009 年至 2014 年的 LCH 患者。患者接受每周一次的长春新碱和泼尼松治疗，共 25 周，用于 RO+。单部位（SS）和多系统（MS）且无风险器官受累（RO-）的患者从第 13 周开始接受每 3 周一次的脉冲治疗，直至第 25 周。维持治疗为每 3 周一次的长春新碱和 5 天一次的泼尼松脉冲治疗，每天 6-巯基嘌呤（60mg/m2）和每周甲氨蝶呤（15mg/m2），用于 RO+和 MSRO-分别为 18 个月和 9 个月。RO+在第 1 年的每个 28 天周期中还接受 21 天的口服依托泊苷（50mg/m2）。

结果

分析了 50 例连续患者。中位年龄为 36 个月（4-189 个月）。SS、MSRO-和 RO+分别为 29 例（58%）、12 例（24%）和 9 例（18%）。4 例失访，被排除在进一步评估之外。在第 6 周的反应评估时，24 例（52%）无活动性疾病（NAD），17 例（37%）AD 改善（AD 为活动性疾病），1 例（2%）AD 恶化。RO+中，8 例（66.6%）AD 改善，3 例（25%）NAD。45 例患者在第 12 周时 NAD。3 例患者复发。中位随访 39 个月（8-84 个月）后，5 年无事件生存率为 85.6%（RO-和 SS），RO+为 100%。1 例因无关原因缓解后死亡，总生存率为 97%。