Graduate School of Medicine, Osaka City University, Osaka, Japan.
J Exp Clin Cancer Res. 2011 Apr 10;30(1):36. doi: 10.1186/1756-9966-30-36.
There has been insufficient examination of the factors affecting long-term survival of more than 5 years in patients with leukemia that is not in remission at transplantation.
We retrospectively analyzed leukemia not in remission at allogeneic hematopoietic cell transplantation (allo-HCT) performed at our institution between January 1999 and July 2009. Forty-two patients with a median age of 39 years received intensified conditioning (n = 9), standard (n = 12) or reduced-intensity conditioning (n = 21) for allo-HCT. Fourteen patients received individual chemotherapy for cytoreduction during the three weeks prior to reduced-intensity conditioning. Diagnoses comprised acute leukemia (n = 29), chronic myeloid leukemia-accelerated phase (n = 2), myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) (n = 10) and plasma cell leukemia (n = 1). In those with acute leukemia, cytogenetic abnormalities were intermediate (44%) or poor (56%). The median number of blast cells in bone marrow (BM) was 26.0% (range; 0.2-100) before the start of chemotherapy for allo-HCT. Six patients had leukemic involvement of the central nervous system. Stem cell sources were related BM (7%), related peripheral blood (31%), unrelated BM (48%) and unrelated cord blood (CB) (14%).
Engraftment was achieved in 33 (79%) of 42 patients. Median time to engraftment was 17 days (range: 9-32). At five years, the cumulative probabilities of acute graft-versus-host disease (GVHD) and chronic GVHD were 63% and 37%, respectively. With a median follow-up of 85 months for surviving patients, the five-year Kaplan-Meier estimates of leukemia-free survival rate and overall survival (OS) were 17% and 19%, respectively. At five years, the cumulative probability of non-relapse mortality was 38%. In the univariable analyses of the influence of pre-transplant variables on OS, poor-risk cytogenetics, number of BM blasts (>26%), MDS overt AML and CB as stem cell source were significantly associated with worse prognosis (p = .03, p = .01, p = .02 and p < .001, respectively). In addition, based on a landmark analysis at 6 months post-transplant, the five-year Kaplan-Meier estimates of OS in patients with and without prior history of chronic GVHD were 64% and 17% (p = .022), respectively.
Graft-versus-leukemia effects possibly mediated by chronic GVHD may have played a crucial role in long-term survival in, or cure of active leukemia.
对于在移植时未缓解的白血病患者，其 5 年以上长期生存的影响因素尚未得到充分研究。
我们回顾性分析了 1999 年 1 月至 2009 年 7 月期间我院所有接受异基因造血细胞移植（allo-HCT）的未缓解白血病患者。42 例患者中位年龄 39 岁，接受强化预处理（n=9）、标准预处理（n=12）或减低强度预处理（n=21）。14 例患者在接受减低强度预处理前的 3 周内接受了个体化化疗进行细胞减灭。诊断包括急性白血病（n=29）、慢性髓系白血病加速期（n=2）、骨髓增生异常综合征/急性髓系白血病（MDS/AML）（n=10）和浆细胞白血病（n=1）。在急性白血病患者中，细胞遗传学异常为中危（44%）或高危（56%）。allo-HCT 开始前骨髓（BM）中 blast 细胞的中位数为 26.0%（范围 0.2-100）。6 例患者有中枢神经系统白血病累及。干细胞来源为亲缘 BM（7%）、亲缘外周血（31%）、无关 BM（48%）和无关 cord blood（CB）（14%）。
42 例患者中有 33 例（79%）获得了 engraftment。中位 engraftment 时间为 17 天（范围 9-32 天）。在 5 年时，急性移植物抗宿主病（GVHD）和慢性 GVHD 的累积发生率分别为 63%和 37%。在对存活患者的中位随访 85 个月时，5 年无白血病生存率和总生存率（OS）分别为 17%和 19%。在 5 年时，非复发死亡率的累积概率为 38%。在移植前变量对 OS 的单变量分析中，高危细胞遗传学、BM blast 数量（>26%）、MDS 转化为 AML 和 CB 作为干细胞来源与预后不良显著相关（p=0.03、p=0.01、p=0.02 和 p<0.001）。此外，基于移植后 6 个月的 landmark 分析，有和无慢性 GVHD 既往史患者的 5 年 OS 估计值分别为 64%和 17%（p=0.022）。
慢性 GVHD 介导的移植物抗白血病效应可能在活跃性白血病的长期生存或治愈中发挥了关键作用。
