Outcome of Down Syndrome (DS) Children with Acute Myeloid Leukemia (AML) or Myelodysplasia (MDS) Treated with a Uniform Prospective Clinical Trial - Initial Report of the COG Trial A2971.
Outcome of Down Syndrome (DS) Children with Acute Myeloid Leukemia (AML) or Myelodysplasia (MDS) Treated with a Uniform Prospective Clinical Trial - Initial Report of the COG Trial A2971.
复制标题
患有急性髓性白血病 (AML) 或骨髓增生异常 (MDS) 的唐氏综合症 (DS) 儿童接受统一前瞻性临床试验的结果 - COG 试验 A2971 的初步报告。
DOI：
--
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
R. Arceci
中科院分区：
文献类型：
--
作者：
A. Gamis;T. Alonzo;J. Hilden;R. Gerbing;T. Loew;Lois Hathaway;L. Mcgavran;D. Barnard;J. Taub;Y. Ravindranath;F. Smith;R. Arceci
与患有 AML 的非 DS 儿童相比，患有 AML 的 DS 儿童具有更好的结果。对于 COG A2971，依托泊苷、地塞米松以及先前 CCG 2891 试验中使用的标准定时 DCTER 方案的 3 个月维持疗程被取消。从1999年到2003年，A2971招募了130名患有AML（n = 86）或MDS（N = 44）的DS患者。中位随访时间为 1253 天 (290 – 2140)。 16 名患者此前已入组该试验的 TMD（短暂性骨髓增生性疾病）组，并在后来出现 AML 或 MDS 时转移至该治疗组。诱导包括 2 个疗程（IND C1 和 C2），每个疗程 2 个周期，硫鸟嘌呤 PO，AraC 和道诺霉素，96 小时输注（CI-TAD）。巩固（CON），随后密集定时高剂量 AraC 和 L-天冬酰胺酶，随后每周 IT AraC × 3。诊断时的中位年龄为 1.6 岁 (y) (0.3-13.6)，其中 0-2 岁组有 85 人，2-4 岁组有 39 人，4 岁以上有 6 人。 CBC 中值：WBC：6,200 (900–164,900)，Hgb：9 (2.5–16.8)，血小板：29,000 (2,000–325,000)。没有患者在诊断时患有中枢神经系统疾病或复发。诱导缓解可评估为 108 分。 84% 和 8% 的患者获得 CR 和 PR，6.5% 的患者出现疾病进展，诱导期间有 1 例死亡（p=NS vs 2891）。在 IND C1、IND C2 和 CON 期间，分别有 55%、29% 和 54% 的患者报告至少一种非血液学毒性。 IND 1、IND 2、CON 中分别观察到以下毒性：粘膜炎 7%、0% 和 10%；感染性并发症，包括未识别微生物的中性粒细胞减少性发热 42%、20%、42%；高血糖7%、0%、5%；肺部 9%、3%、7%。 2891 和 A2971 试验之间的毒性没有临床显着差异。在所有患者中，3 年 OS 为 84%（相对于 2891 例中的 80%），EFS 为 79%（相对于 77%），TRM 为 3%（相对于 4%），DFS（来自 CR）为 90%（相对于 85%）。在 CCG 2891 中，年龄增长是一个不利的危险因素。按年龄组 0–2、2–4 和 >4 岁，A2971 3y OS 分别为 89、82 和 33%，3y EFS 分别为 83、79 和 33%，DFS 分别为 91、92 和 33%（年龄 0–2 与 2–4 岁，所有 p=NS，OS 趋势除外：p=.007）。在 CCG 2891 中，按年龄组划分的 3 年结果为： OS：86%、75% 和 42%； EFS：86%、68%、33%； DFS：92%、81% 和 43%。试验之间的生存率有所改善，特别是在 2-4 岁儿童中，但与年龄组相比，没有任何统计学意义。在先前入组的 16 名 TMD 患者中，诊断 AML/MDS 时的中位年龄为 1.0 岁，并且全部获得 CR。 14 名患者在 2 岁之前被诊断，并且与年龄相似的新诊断患者具有相似的诊断结果和结果 (p=NS)。该报告表明，消除了 2 种药物并维持治疗，且存活率没有降低。年龄作为不利危险因素仍然存在，但在本研究中对 2 至 4 岁组的影响较小，并且未能始终达到统计显着性。由于操作系统和 EFS 仍然存在
DS children with AML have a superior outcome as compared to nonDS children with AML. For COG A2971, etoposide, dexamethasone, & the 3 month maintenance course from the standard timing DCTER regimen used in the prior CCG 2891 trial, were eliminated. From 1999–2003, A2971 enrolled 130 DS patients(pts) with AML(n= 86) or MDS(N=44). Median followup was 1253 days (290 – 2140). Sixteen pts had previously been enrolled in this trial’s TMD (transient myeloproliferative disorder) arm & transferred to this treatment arm when they later developed AML or MDS. Induction consisted of 2 courses(IND C1 & C2) of 2 cycles each of thioguanine PO, with AraC & daunomycin by 96 hour infusion(CI-TAD). Consolidation(CON) followed with intensively timed high dose AraC & L-asparaginase followed by IT AraC weekly ×3. Median age at diagnosis was 1.6 years (y) (0.3–13.6) with 85 in the 0–2y group, 39 ages 2–4y, & 6 over 4y of age. Median CBC values: WBC: 6,200 (900–164,900), hgb: 9 (2.5–16.8), & platelets: 29,000 (2,000–325,000). No patient had CNS disease at diagnosis or relapse. Induction remission was evaluable in 108 pts. CR & PR were achieved in 84% & 8%, progressive disease occurred in 6.5%, and there was one death during induction(p=NS vs 2891). At least one non-hematologic toxicity was reported in 55%, 29%, and 54% of pts during IND C1, IND C2, and CON, respectively. The following toxicities were seen respectively in IND 1, IND 2, CON: mucositis 7%, 0%, & 10%; infectious complications including neutropenic fever without an identified organism 42%, 20%, 42%; hyperglycemia 7%, 0%, 5%; pulmonary 9%, 3%, 7%. There were no clinically significant differences in toxicity between 2891 & A2971 trials. Among all pts, 3y OS was 84%(vs 80% in 2891), EFS was 79%(vs 77%), TRM was 3%(vs 4%), & DFS(from CR) was 90%(vs 85%). In CCG 2891, increasing age was an adverse risk factor. By age groups 0–2, 2–4, & >4y, A2971 3y OS was 89, 82, & 33%, 3y EFS was 83, 79, & 33%, & DFS was 91, 92, & 33%, respectively(ages 0–2 vs 2–4y, all p=NS, except OS trend: p=.007). In CCG 2891, these 3y outcomes by age group were: OS: 86, 75, & 42%; EFS: 86, 68, & 33%; and DFS: 92, 81, & 43%. Improvements in survival were seen between trials, particularly in the 2–4 yo’s, but none were statistically significant when compared by age cohorts. Among the 16 previously enrolled with TMD, median age at AML/MDS diagnosis was 1.0 y and all achieved CR. Fourteen were diagnosed before age 2y & had similar diagnostic findings and outcomes to newly diagnosed pts of similar age(p=NS). This report shows that the elimination of 2 agents and maintenance was achieved without a decrease in survival. Age as an adverse risk factor persisted though with less impact in the 2 to 4 year old group in this study and failed to consistently reach statistical significance. As OS & EFS remain