Silverman L B, McLean T W, Gelber R D, Donnelly M J, Gilliland D G, Tarbell N J, Sallan S E
Children's Hospital, the Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Cancer. 1997 Dec 15;80(12):2285-95.
Infants with acute lymphoblastic leukemia (ALL) have a very poor prognosis. Since 1985, we have intensified therapy for infants with ALL by including a month of high dose multiagent chemotherapy after remission induction.
Between 1985 and 1995, we treated 23 infants (age < 12 months). We compared the presenting characteristics and outcomes of these infants with the 11 infants treated on our protocols between 1973 and 1985, an era prior to the intensification of therapy. Available bone marrow samples from infants treated since 1985 were analyzed for the presence of MLL gene rearrangements by Southern blot analyses and for TEL-AML1 gene fusion by reverse transcriptase-polymerase chain reaction.
With a median follow-up of 5.6 years, the 50-month event free survival (EFS) (+/- standard error) for the 23 infants was 54 +/- 11%, a significant improvement (P = 0.001) compared with the outcome for the 11 infants treated on our protocols prior to 1985 (EFS = 9 +/- 9%). Of the seven infants found to have a rearranged MLL gene, three (43%) remained in first complete remission. None of the nine infant bone marrow specimens tested had evidence of TEL-AML1 gene fusion. The intensified therapy was complicated by a high incidence of infections, including septicemia in 52% of patients and Pneumocystis carinii pneumonitis in 22% of patients. Late effects identified in the 13 long term survivors (median age, 6 years) included developmental delay and learning disabilities of varying severity (82% of evaluable patients), asymptomatic cataracts (67%), asymptomatic echocardiographic abnormalities (30%), obesity (27%), and short stature (18%).
Intensification of therapy significantly improved the EFS of infants with ALL compared with previous, less intensive regimens and with the experience of other investigators. Future treatment for infants should attempt to improve efficacy while minimizing toxicity.
急性淋巴细胞白血病（ALL）婴儿的预后非常差。自1985年以来，我们通过在缓解诱导后增加一个月的高剂量多药化疗，加强了对ALL婴儿的治疗。
1985年至1995年期间，我们治疗了23名婴儿（年龄<12个月）。我们将这些婴儿的临床表现和预后与1973年至1985年期间按照我们的方案治疗的11名婴儿进行了比较，1973年至1985年是强化治疗之前的时期。对1985年以来接受治疗的婴儿的可用骨髓样本进行Southern印迹分析，以检测MLL基因重排的存在，并通过逆转录聚合酶链反应检测TEL-AML1基因融合情况。
中位随访5.6年，23名婴儿的50个月无事件生存率（EFS）（±标准误）为54±11%，与1985年之前按照我们的方案治疗的11名婴儿的预后（EFS = 9±9%）相比有显著改善（P = 0.001）。在发现有MLL基因重排的7名婴儿中，3名（43%）仍处于首次完全缓解状态。检测的9份婴儿骨髓标本中均无TEL-AML1基因融合的证据。强化治疗的并发症是感染发生率高，包括52%的患者发生败血症，22%的患者发生卡氏肺孢子虫肺炎。在13名长期存活者（中位年龄6岁）中发现的晚期效应包括不同严重程度的发育迟缓及学习障碍（82%的可评估患者）、无症状性白内障（67%）、无症状性超声心动图异常（30%）、肥胖（27%）和身材矮小（18%）。
与之前强度较低的治疗方案及其他研究者的经验相比，强化治疗显著提高了ALL婴儿的EFS。未来对婴儿的治疗应在尽量减少毒性的同时提高疗效。
