Lang Peter, Greil Johann, Bader Peter, Handgretinger Rupert, Klingebiel Thomas, Schumm Michael, Schlegel Paul-Gerhard, Feuchtinger Tobias, Pfeiffer Matthias, Scheel-Walter Hans, Führer Monika, Martin David, Niethammer Dietrich
Children's University Hospital, University of Tuebingen, Germany.
Blood Cells Mol Dis. 2004 Nov-Dec;33(3):281-7. doi: 10.1016/j.bcmd.2004.08.017.
We present an update of our results with transplantation of highly purified stem cells from one to three loci mismatched parental donors. Sixty-three pediatric patients with acute lymphoblastic leukemias (n = 32), acute myeloid, chronic myeloid and myelomonocytic leukemias (n = 13), myelodysplastic syndromes (n = 4), lymphomas (n = 4), and various nonmalignant diseases (n = 10) underwent transplantation. Mobilized peripheral-blood stem cells were selected with either anti-CD34- or anti-CD133-coated microbeads. Patients received a median of 19.5 x 10(6) purified cells and <25,000 CD3+ T lymphocytes per kilogram, with no regular posttransplant pharmacological immunosuppression. Engraftment occurred in 98% of patients (primary sustained engraftment, 83%; engraftment after reconditioning/stem cell boosts, 15%). Moreover, all survivors but one had a stable three-lineage engraftment with a median follow up of 4.1 years (range 0.6-8 years). Primary acute graft-versus-host disease (GvHD) grade II was seen in only 7% of patients. No severe primary acute GvHD grades III-IV occurred. Thirteen percent of the patients developed transient chronic GvHD. Probability of disease-free survival (DFS) at 3 years was 60% for patients with nonmalignant diseases and 48% for patients with acute lymphatic leukemia (ALL)/non-Hodgkin lymphoma (NHL) in complete remission (CR)1-3. None of the ALL/NHL patients with active disease survived. Children with acute and chronic myeloid leukemias had a poorer outcome (3-year DFS = 18%), whereas two of four patients with myelodysplastic syndrome (MDS) are alive. Relapse probability of the whole group was not significantly increased when compared to a historical control group. The incidence of lethal viral infections was 18% between 1995 and 2002 and has since been reduced to 8% by the introduction of new therapeutic strategies. In summary, the use of stem cells from haploidentical parental donors should be strongly considered in all children who need transplantation but lack an identical donor.
我们展示了使用来自一个至三个位点不匹配的亲代供体的高度纯化干细胞进行移植的最新结果。63例患有急性淋巴细胞白血病（n = 32）、急性髓系白血病、慢性髓系白血病和骨髓单核细胞白血病（n = 13）、骨髓增生异常综合征（n = 4）、淋巴瘤（n = 4）以及各种非恶性疾病（n = 10）的儿科患者接受了移植。使用抗CD34或抗CD133包被的微珠筛选动员的外周血干细胞。患者每千克体重接受中位数为19.5×10⁶个纯化细胞和少于25,000个CD3⁺T淋巴细胞，移植后未进行常规的药物免疫抑制。98%的患者实现了植入（初次持续植入，83%；预处理/干细胞增强后植入，15%）。此外，除1例幸存者外，所有幸存者均有稳定的三系植入，中位随访时间为4.1年（范围0.6 - 8年）。仅7%的患者出现原发性急性移植物抗宿主病（GvHD）II级。未发生严重的原发性急性GvHD III - IV级。13%的患者发生了短暂性慢性GvHD。非恶性疾病患者3年无病生存率（DFS）为60%，完全缓解（CR）1 - 3期的急性淋巴细胞白血病（ALL）/非霍奇金淋巴瘤（NHL）患者为48%。所有患有活动性疾病的ALL/NHL患者均未存活。急性和慢性髓系白血病患儿的预后较差（3年DFS = 18%），而4例骨髓增生异常综合征（MDS）患者中有2例存活。与历史对照组相比，整个组的复发概率没有显著增加。1995年至2002年间，致命病毒感染的发生率为18%，自引入新的治疗策略后已降至8%。总之，对于所有需要移植但缺乏同基因供体的儿童，应强烈考虑使用单倍体亲代供体的干细胞。
