Krijanovski O I, Hill G R, Cooke K R, Teshima T, Crawford J M, Brinson Y S, Ferrara J L
Department of Pediatric Oncology, Dana Farber Cancer Institute, Children's Hospital, and Harvard Medical School, Boston, MA, USA.
Blood. 1999 Jul 15;94(2):825-31.
The major obstacles to successful outcome after allogeneic bone marrow transplantation (BMT) for leukemia remain graft-versus-host disease (GVHD) and leukemic relapse. Improved survival after BMT therefore requires more effective GVHD prophylaxis that does not impair graft-versus-leukemia (GVL) effects. We studied the administration of human recombinant keratinocyte growth factor (KGF) in a well- characterized murine BMT model for its effects on GVHD. KGF administration from day -3 to +7 significantly reduced GVHD mortality and the severity of GVHD in the gastrointestinal (GI) tract, reducing serum lipopolysaccharide (LPS) and tumor necrosis factor (TNF)alpha levels, but preserving donor T-cell responses (cytotoxic T lymphocyte [CTL] activity, proliferation, and interleukin [IL]-2 production) to host antigens. When mice received lethal doses of P815 leukemia cells at the time of BMT, KGF treatment significantly decreased acute GVHD compared with control-treated allogeneic mice and resulted in a significantly improved leukemia-free survival (42% v 4%, P <.001). KGF administration thus offers a novel approach to the separation of GVL effects from GVHD.
异基因骨髓移植（BMT）治疗白血病后获得成功结局的主要障碍仍然是移植物抗宿主病（GVHD）和白血病复发。因此，提高BMT后的生存率需要更有效的GVHD预防措施，且不损害移植物抗白血病（GVL）效应。我们在一个特征明确的小鼠BMT模型中研究了人重组角质形成细胞生长因子（KGF）的给药情况，以观察其对GVHD的影响。从第-3天至+7天给予KGF可显著降低GVHD死亡率以及胃肠道（GI）中GVHD的严重程度，降低血清脂多糖（LPS）和肿瘤坏死因子（TNF）α水平，但保留供体T细胞对宿主抗原的反应（细胞毒性T淋巴细胞[CTL]活性、增殖和白细胞介素[IL]-2产生）。当小鼠在BMT时接受致死剂量的P815白血病细胞时，与对照处理的同种异体小鼠相比，KGF治疗显著降低了急性GVHD，并导致无白血病生存率显著提高（42%对4%，P<.001）。因此，给予KGF为将GVL效应与GVHD分离提供了一种新方法。
