在儿童癌症组的两项连续试验中接受治疗的急性淋巴细胞白血病婴儿的治疗结果及预后因素

Treatment outcome and prognostic factors for infants with acute lymphoblastic leukemia treated on two consecutive trials of the Children's Cancer Group.

作者信息

Reaman G H, Sposto R, Sensel M G, Lange B J, Feusner J H, Heerema N A, Leonard M, Holmes E J, Sather H N, Pendergrass T W, Johnstone H S, O'Brien R T, Steinherz P G, Zeltzer P M, Gaynon P S, Trigg M E, Uckun F M

机构信息

Children's National Medical Center and George Washington University School of Medicine, Washington, DC, USA.

出版信息

J Clin Oncol. 1999 Feb;17(2):445-55. doi: 10.1200/JCO.1999.17.2.445.

DOI:10.1200/JCO.1999.17.2.445

PMID:10080584

Abstract

PURPOSE

Infants represent a very poor risk group for acute lymphoblastic leukemia (ALL). We report treatment outcome for such patients treated with intensive therapy on consecutive Children's Cancer Group (CCG) protocols.

PATIENTS AND METHODS

Between 1984 and 1993, infants with newly diagnosed ALL were enrolled onto CCG-107 (n = 99) and CCG-1883 (n = 135) protocols. Postconsolidation therapy was more intensive on CCG-1883. On both studies, prophylactic treatment of the CNS included both high-dose systemic chemotherapy and intrathecal therapy, in contrast to whole-brain radiotherapy, which was used in earlier studies.

RESULTS

Most patients (>95%) achieved remission with induction therapy. The most frequent event was a marrow relapse (46 patients on CCG-107 and 66 patients on CCG- 1883). Four-year event-free survival was 33% (SE = 4.7%) on CCG-107 and 39% (SE = 4.2%) on CCG- 1883. Both studies represent an improvement compared with a 22% (SE = 5.1%) event-free survival for historical controls. Four-year cumulative probabilities of any marrow relapse or an isolated CNS relapse were, respectively, 49% (SE = 5%) and 9% (SE = 3%) on CCG-107 and 50% (SE = 5%) and 3% (SE = 2%) on CCG-1883, compared with 63% (SE = 6%) and 5% (SE = 3%) for the historical controls. Independent adverse prognostic factors were age less than 3 months, WBC count of more than 50,000/microL, CD10 negativity, slow response to induction therapy, and presence of the translocation t(4;11).

CONCLUSION

Outcome for infants on CCG-107 and CCG- 1883 improved, compared with historical controls. Marrow relapse remains the primary mode of failure. Isolated CNS relapse rates are low, indicating that intrathecal chemotherapy combined with very-high-dose systemic therapy provides adequate protection of the CNS. The overall unsatisfactory outcome observed for the infant ALL population warrants the future use of novel alternative therapies.

摘要

目的

婴儿是急性淋巴细胞白血病（ALL）的高危群体。我们报告了连续采用儿童癌症组（CCG）方案进行强化治疗的此类患者的治疗结果。

患者与方法

1984年至1993年间，新诊断为ALL的婴儿被纳入CCG - 107方案（n = 99）和CCG - 1883方案（n = 135）。CCG - 1883方案的巩固治疗强度更大。在两项研究中，中枢神经系统的预防性治疗包括高剂量全身化疗和鞘内治疗，这与早期研究中使用的全脑放疗不同。

结果

大多数患者（>95%）通过诱导治疗实现缓解。最常见的事件是骨髓复发（CCG - 107方案中有46例患者，CCG - 1883方案中有66例患者）。CCG - 107方案的4年无事件生存率为33%（标准误 = 4.7%），CCG - 1883方案为39%（标准误 = 4.2%）。与历史对照的22%（标准误 = 5.1%）无事件生存率相比，两项研究均有改善。CCG - 107方案中任何骨髓复发或孤立性中枢神经系统复发的4年累积概率分别为49%（标准误 = 5%）和9%（标准误 = 3%），CCG - 1883方案分别为50%（标准误 = 5%）和3%（标准误 = 2%），而历史对照分别为63%（标准误 = 6%）和5%（标准误 = 3%）。独立的不良预后因素包括年龄小于3个月、白细胞计数超过50,000/μL、CD10阴性、诱导治疗反应缓慢以及存在t(4;11)易位。