Söderdahl Gunnar, Barkholt Lisbeth, Hentschke Patrik, Mattsson Jonas, Uzunel Mehmet, Ericzon Bo-Göran, Ringdén Olle
Department of Transplantation Surgery, B56, Huddinge University Hospital, S-141 86 Stockholm, Sweden. gunnar.soderdahl@ karo.ki.se
Transplantation. 2003 Apr 15;75(7):1061-6. doi: 10.1097/01.TP.0000058515.02300.5E.
Tumor recurrence after orthotopic liver transplantation (OLT) in patients with advanced primary liver cancer is common. To achieve an adjuvant graft-versus-tumor effect, the authors investigated whether transplantation of allogeneic peripheral blood stem cells (PSCT) after OLT can induce sustained complete donor chimerism.
Five patients with advanced primary liver cancer were included in the trial. None of the patients had signs of extrahepatic tumor before OLT. However, overall, the extent of surgery, as judged by morphologic examination of the explanted liver, was considered inadequate. A nonmyeloablative preparative regimen of fludarabine combined with total-body irradiation or cyclophosphamide preceded the allogeneic PSCT, which was then performed 16 to 135 days after OLT with human leukocyte antigen-matched donors. Mixed chimerism was monitored weekly by polymerase chain reaction of variable number tandem repeats after PSCT.
In two patients, no engraftment of donor cells was seen, whereas one rejected the cells 2 months after PSCT. In two of the patients, a stable mixed donor chimerism was established. A mild transient graft-versus-host reaction was also noted in two patients. Three of the patients died of progressive disease 7 to 9 months after OLT. The other two are presently alive without recurrence at a follow-up of 26 and 10 months, respectively.
These data suggest that PSCT after OLT is feasible, with low transplant-related morbidity. The rate of nonengraftment or rejection of the transplanted stem cells in this group of patients was three of five. An augmented pretreatment to prevent donor T-cell rejection seems to be necessary in this setting.
晚期原发性肝癌患者原位肝移植（OLT）后肿瘤复发很常见。为实现辅助性移植物抗肿瘤效应，作者研究了OLT后同种异体外周血干细胞移植（PSCT）是否能诱导持续的完全供体嵌合状态。
5例晚期原发性肝癌患者纳入试验。所有患者在OLT前均无肝外肿瘤迹象。然而，总体而言，根据切除肝脏的形态学检查判断，手术范围被认为不充分。在同种异体PSCT前采用氟达拉滨联合全身照射或环磷酰胺的非清髓性预处理方案，然后在OLT后16至135天与人类白细胞抗原匹配的供体进行PSCT。PSCT后每周通过可变数目串联重复序列的聚合酶链反应监测混合嵌合状态。
2例患者未见供体细胞植入，1例在PSCT后2个月排斥细胞。2例患者建立了稳定的混合供体嵌合状态。2例患者还出现了轻度短暂的移植物抗宿主反应。3例患者在OLT后7至9个月死于疾病进展。另外2例目前存活，分别随访26个月和10个月无复发。
这些数据表明OLT后PSCT是可行的，移植相关发病率低。该组患者中移植干细胞未植入或被排斥的发生率为五分之三。在这种情况下，似乎有必要加强预处理以防止供体T细胞排斥。
