Bordigoni P, Esperou H, Souillet G, Pico J, Michel G, Lacour B, Reiffers J, Sadoun A, Rohrlich P, Jouet J P, Milpied N, Lutz P, Plouvier E, Cornu G, Vannier J P, Gandemer V, Rubie H, Gratecos N, Leverger G, Stephan J L, Boutard P, Vernant J P
Unité de Transplantation Médullaire, Hôpital d'Enfants, Nancy, France.
Br J Haematol. 1998 Aug;102(3):656-65. doi: 10.1046/j.1365-2141.1998.00825.x.
We investigated the use of a new conditioning regimen followed by allogeneic bone marrow transplantation (BMT) for treating children with acute lymphoblastic leukaemia (ALL) after relapse within 6 months of the completion of therapy. One hundred and sixteen children with acute lymphoblastic leukaemia in second or subsequent complete remission (CR) underwent allogeneic bone marrow transplantation from HLA-identical siblings after a preparative regimen comprising total body irradiation (TBI), high-dose cytosine arabinoside and melphalan (TAM regimen). The Kaplan-Meier product-limit estimate (mean +/- SE) of disease-free survival (DFS) at 7 years was 59.5 +/- 9% (95% confidence interval). The estimated chance of relapse was 22.5 +/- 15% with a median follow-up of 88.5 months (range 51-132). 26 patients (22.4%) died with no evidence of recurrent leukaemia, mainly from interstitial pneumonitis, veno-occlusive disease or acute graft-versus-host disease (GVHD). Three factors significantly affected DFS: acute GVHD. site of relapse and, for children in second remission after a marrow relapse, the disease status at the time of transplantation. The DFS were 59.02 +/- 12.6%, 37.5 +/- 19.8% and 774 +/- 15% among patients in CR2 after a marrow relapse, in CR3 or in untreated partial marrow relapse, and in CR2 after an isolated CNS relapse, respectively. The lowest DFS was seen in children with acute GVHD grades 3-4. Two significant factors were associated with relapse: the marrow status at the time of transplantation and chronic GVHD. The relapse rate was lower among children in CR2 or with chronic GVHD. We conclude that transplantation after the TAM regimen is an effective therapy for this population with acceptable toxicity, particularly for children in second remission after a very early marrow relapse, or those with early isolated CNS involvement.
我们研究了采用一种新的预处理方案后进行异基因骨髓移植(BMT)治疗在治疗完成后6个月内复发的急性淋巴细胞白血病(ALL)儿童的情况。116例处于第二次或后续完全缓解(CR)期的急性淋巴细胞白血病儿童,在接受了包括全身照射(TBI)、大剂量阿糖胞苷和美法仑的预处理方案(TAM方案)后,接受了来自HLA相同同胞的异基因骨髓移植。7年无病生存率(DFS)的Kaplan-Meier乘积限估计值(均值±标准误)为59.5±9%(95%置信区间)。估计复发几率为22.5±15%,中位随访时间为88.5个月(范围51 - 132个月)。26例患者(22.4%)死亡,无白血病复发证据,主要死于间质性肺炎、静脉闭塞性疾病或急性移植物抗宿主病(GVHD)。三个因素显著影响DFS:急性GVHD、复发部位,以及对于骨髓复发后处于第二次缓解期的儿童,移植时的疾病状态。在骨髓复发后处于CR2期、CR3期或未治疗的部分骨髓复发期以及孤立性中枢神经系统复发后处于CR2期的患者中DFS分别为59.02±12.6%、37.5±19.8%和77.4±15%。急性GVHD 3 - 4级的儿童DFS最低。两个显著因素与复发相关:移植时的骨髓状态和慢性GVHD。CR2期儿童或患有慢性GVHD的儿童复发率较低。我们得出结论,TAM方案后的移植对于该人群是一种有效的治疗方法,毒性可接受,特别是对于极早期骨髓复发后处于第二次缓解期的儿童或早期孤立性中枢神经系统受累的儿童。