Woods William G, Barnard Dorothy R, Alonzo Todd A, Buckley Jonathan D, Kobrinsky Nathan, Arthur Diane C, Sanders Jean, Neudorf Steven, Gold Stuart, Lange Beverly J
AFLAC Cancer Center, Emory University/Children's Healthcare, Atlanta, GA, USA.
J Clin Oncol. 2002 Jan 15;20(2):434-40. doi: 10.1200/JCO.2002.20.2.434.
We report the first large prospective study of children with myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML) treated in a uniform fashion on Children's Cancer Group protocol 2891.
Ninety children with JMML, various forms of MDS, or acute myeloid leukemia (AML) with antecedent MDS were treated with a five-drug induction regimen (standard or intensive timing). Patients achieving remission were allocated to allogeneic bone marrow transplantation (BMT) if a matched family donor was available. All other patients were randomized between autologous BMT and aggressive nonmyeloablative chemotherapy. Results were compared with patients with de novo AML.
Patients with JMML and refractory anemia (RA) or RA-excess blasts (RAEB) exhibited high induction failure rates and overall remission of 58% and 48%, respectively. Remission rates for patients with RAEB in transformation (RAEB-T) (69%) or antecedent MDS (81%) were similar to de novo AML (77%). Actuarial survival rates at 6 years were as follows: JMML, 31% +/- 26%; RA and RAEB, 29% +/- 16%; RAEB-T, 30% +/- 18%; antecedent MDS, 50% +/- 25%; and de novo AML, 45% +/- 3%. For patients achieving remission, long-term survivors were found in those receiving either allogeneic BMT or chemotherapy. The presence of monosomy 7 had no additional adverse effect on MDS and JMML.
Childhood subtypes of MDS and JMML represent distinct entities with distinct clinical outcomes. Children with a history of MDS who present with AML do well with AML-type therapy. Patients with RA or RAEB respond poorly to AML induction therapy. The optimum treatment for JMML remains unknown.
我们报告了第一项关于骨髓增生异常综合征（MDS）和青少年粒单核细胞白血病（JMML）患儿的大型前瞻性研究，这些患儿按照儿童癌症组方案2891以统一方式接受治疗。
90例患有JMML、各种形式的MDS或伴有前驱MDS的急性髓系白血病（AML）的患儿接受了五药诱导方案（标准或强化疗程）治疗。如果有匹配的家庭供者，达到缓解的患者被分配接受异基因骨髓移植（BMT）。所有其他患者在自体BMT和积极的非清髓性化疗之间随机分组。结果与初发AML患者进行比较。
JMML以及难治性贫血（RA）或原始细胞过多的难治性贫血（RAEB）患者表现出较高的诱导失败率，总体缓解率分别为58%和48%。转化中的RAEB（RAEB-T）（69%）或前驱MDS（81%）患者的缓解率与初发AML（77%）相似。6年的精算生存率如下：JMML为31%±26%；RA和RAEB为29%±16%；RAEB-T为30%±18%；前驱MDS为50%±25%；初发AML为45%±3%。对于达到缓解的患者，接受异基因BMT或化疗的患者中均发现了长期存活者。7号染色体单体的存在对MDS和JMML没有额外的不良影响。
MDS和JMML的儿童亚型代表了具有不同临床结局的不同实体。有MDS病史且表现为AML的儿童采用AML型治疗效果良好。RA或RAEB患者对AML诱导治疗反应较差。JMML的最佳治疗方法仍然未知。
