在马拉维资源有限的环境中，晚期儿科成熟B细胞非霍奇金淋巴瘤患者使用高剂量甲氨蝶呤时未进行药物水平监测

High-Dose Methotrexate Usage Without Drug-Level Monitoring in Advanced Pediatric Mature B-Cell Non-Hodgkin Lymphoma in a Resource-Limited Setting in Malawi.

作者信息

Mzikamanda Rizine R, Mulanje Loviisa, McAtee Casey L, Matatiyo Apatsa, Mwale Zoe, Chirwa Grace, Wanda Watipaso, Mpasa Atupele Miranda, Wachepa Stella, Huibers Minke H W, Martin Steve, Tomoka Tamiwe, Mulenga Maurice, Fedoriw Yuri, Mapurisa Gugulethu, Gastier Foster Julie M, El-Mallawany Nader, Westmoreland Katherine D, Wasswa Peter, Allen Carl E, Ozuah Nmazuo

机构信息

Pediatric Hematology-Oncology, Kamuzu Central Hospital, Lilongwe, Malawi.

Baylor College of Medicine Children's Foundation-Malawi, Lilongwe, Malawi.

出版信息

JCO Glob Oncol. 2025 Mar;11:e2400591. doi: 10.1200/GO-24-00591. Epub 2025 Mar 28.

DOI:10.1200/GO-24-00591

PMID:40153690

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12004980/

Abstract

PURPOSE

Excellent survival for advanced (stages II with high lactate dehydrogenase, III, and IV) pediatric mature B-cell non-Hodgkin lymphoma (MB-NHL) has been achieved with intensive regimens, but adoption in sub-Saharan Africa is limited by inadequate supportive care. We provide real-world data on treating advanced MB-NHL with high-dose methotrexate (HD-MTX; ≥1,000 mg/m/cycle) where real-time serum MTX monitoring is unavailable.

METHODS

We identified two cohorts-a retrospective (January 2017-December 2020) cohort treated with 1,000 or 3,000 mg/m/cycle of HD-MTX and a prospective (July 2022-July 2023) cohort-with a modified LMB96 protocol containing 3,000 mg/m/cycle of HD-MTX. All doses of HD-MTX were given over 3 hours. Estimates of 12-month event-free survival (EFS) and overall survival (OS) were calculated with abandonment as an event. Clinical toxicity data were available for the prospective cohort.

RESULTS

The retrospective cohort had 108 patients who received HD-MTX 1,000 mg/m (n = 98, 91%) or 3,000 mg/m per cycle. The 12-month EFS and OS were 39% (95% CI, 30 to 50) and 54% (95% CI, 44 to 64), respectively. HD-MTX at 3,000 mg/m had superior EFS: 69% (95% CI, 49 to 96) versus 33% (95% CI, 24 to 46), = .004. The prospective cohort had 38 patients. Two ≥grade 3 mucositis, one acute kidney injury, and three treatment-related deaths (8%) occurred. Seven (18%) abandoned treatment. With a median follow-up of 14.5 months, 12-month EFS and OS were 45% (95% CI, 32 to 65) and 59% (95% CI, 45 to 79), respectively. Most relapses were stage IV: EFS 20% versus 51% (non-stage IV; = .057). Severe malnutrition was associated with OS of 33% versus 58% (normal) or 76% (moderate; = .055).

CONCLUSION

HD-MTX dosed at 3,000 mg/m/cycle is feasible in low-resource settings where routine MTX monitoring is unavailable. Stage IV disease and severe malnutrition may contribute to poorer outcomes.

摘要

目的

采用强化治疗方案已使晚期（乳酸脱氢酶水平高的II期、III期和IV期）儿童成熟B细胞非霍奇金淋巴瘤（MB - NHL）获得了良好的生存率，但撒哈拉以南非洲地区因支持治疗不足，该方案的采用受到限制。我们提供了在无法进行实时血清甲氨蝶呤（MTX）监测的情况下，使用大剂量甲氨蝶呤（HD - MTX；≥1000 mg/m²/周期）治疗晚期MB - NHL的真实世界数据。

方法

我们确定了两个队列——一个回顾性队列（2017年1月至2020年12月），接受1000或3000 mg/m²/周期的HD - MTX治疗，以及一个前瞻性队列（2022年7月至2023年7月），采用改良的LMB96方案，其中包含3000 mg/m²/周期的HD - MTX。所有HD - MTX剂量均在3小时内给予。以放弃治疗作为事件计算12个月无事件生存率（EFS）和总生存率（OS）。前瞻性队列可获得临床毒性数据。

结果

回顾性队列有108例患者，接受每周期1000 mg/m²（n = 98，91%）或3000 mg/m²的HD - MTX治疗。12个月的EFS和OS分别为39%（95%CI，30至50）和54%（95%CI，44至64）。3000 mg/m²的HD - MTX具有更好的EFS：69%（95%CI，49至96）对33%（95%CI，24至46），P = 0.004。前瞻性队列有38例患者。发生了2例≥3级粘膜炎、1例急性肾损伤和3例治疗相关死亡（8%）。7例（18%）放弃治疗。中位随访14.5个月时，12个月的EFS和OS分别为45%（95%CI，32至65）和59%（95%CI，45至79）。大多数复发为IV期：EFS为20%对51%（非IV期；P = 0.057）。严重营养不良与33%的OS相关，而正常营养状态者为58%，中度营养不良者为76%（P = 0.055）。