Christina Peters, Susanne Matthes-Martin, and Ulrike Poetschger, St Anna Children's Hospital, Vienna, Austria; Martin Schrappe, University Medical Center Schleswig-Holstein and Christian-Albrechts-University Kiel; André Schrauder, Kinderarztpraxis am Aalborgring, Kiel; Arend von Stackelberg and Wolfram Ebell, Charité-Children's Hospital Berlin, Berlin; Peter Bader and Thomas Klingebiel, Johann Wolfgang Goethe University, Frankfurt; Peter Lang, University Hospital Tübingen, Tübingen; Karl-Walter Sykora and Martin Zimmerman, Hannover Medical School, Hannover; Johanna Schrum, University Medical Center Hamburg-Eppendorf, Hamburg; Bernhard Kremens, University Hospital Essen, Essen; Karoline Ehlert, University Clinic Greifswald, Greifswald; Michael H. Albert, Dr. von Hauner University Children's Hospital, München; Roland Meisel, University Hospital Düsseldorf, Düsseldorf; Wolfgang Holter, Children's University Hospital Erlangen, Erlangen; Brigitte Strahm, University Hospital Freiburg, Freiburg; Bernd Gruhn, University Hospital Jena, Jena; Ansgar Schulz, University Hospital Ulm, Ulm; Wilhelm Woessmann, University Clinic Giessen, Giessen, Germany; and Tayfun Gungor, University Children's Hospital Zürich, Zürich, Switzerland.
J Clin Oncol. 2015 Apr 10;33(11):1265-74. doi: 10.1200/JCO.2014.58.9747. Epub 2015 Mar 9.
Although hematopoietic stem-cell transplantation is widely performed in children with high-risk acute lymphoblastic leukemia (ALL), the influence of donor types is poorly understood. Thus, transplantation outcomes were compared in the prospective multinational Berlin-Frankfurt-Muenster (BFM) study group trial: ALL-SCT-BFM 2003 (Allogeneic Stem Cell Transplantation in Children and Adolescents with Acute Lymphoblastic Leukemia).
After conditioning with total-body irradiation and etoposide, 411 children with high-risk ALL received highly standardized stem-cell transplantations during the first or later remissions. Depending on donor availability, grafts originated from HLA-genoidentical siblings or from HLA-matched unrelated donors who were identified and matched by high-resolution allelic typing and were compatible in at least 9 of 10 HLA loci.
Four-year event-free survival (± standard deviation [SD]) did not differ between patients with transplantations from unrelated or sibling donors (0.67 ± 0.03 v 0.71 ± 0.05; P = .405), with cumulative incidences of nonrelapse mortality (± SD) of 0.10 ± 0.02 and 0.03 ± 0.02 (P = .017) and relapse rates (± SD) of 0.22 ± 0.02 and 0.24 ± 0.04 (P = .732), respectively. Among recipients of transplantations from unrelated donors, no significant differences in event-free survival, overall survival, or nonrelapse mortality were observed between 9/10 and 10/10 matched grafts or between peripheral blood stem cells and bone marrow. The absence of chronic graft-versus-host disease had no effect on event-free survival. Engraftment was faster after bone marrow transplantation from siblings and was associated with fewer severe infections and pulmonary complications.
Outcome among high-risk pediatric patients with ALL after hematopoietic stem-cell transplantation was not affected by donor type. Standardized myeloablative conditioning produced a low incidence of treatment-related mortality and effective control of leukemia.
尽管造血干细胞移植已广泛应用于高危急性淋巴细胞白血病（ALL）患儿，但供者类型的影响仍不清楚。因此，在前瞻性多国柏林-法兰克福-明斯特（BFM）研究组试验：ALL-SCT-BFM 2003（儿童和青少年急性淋巴细胞白血病的异基因造血干细胞移植）中比较了移植结局。
在全身照射和依托泊苷预处理后，411 例高危 ALL 患儿在首次或后续缓解期接受高度标准化的干细胞移植。根据供者的可用性，移植物来源于 HLA 基因相同的同胞或通过高分辨率等位基因分型鉴定和匹配且至少 10 个 HLA 位点中 9 个匹配的 HLA 匹配的无关供者。
无关供者和同胞供者移植的 4 年无事件生存率（±标准偏差[SD]）无差异（0.67 ± 0.03 对 0.71 ± 0.05；P =.405），非复发死亡率（±SD）的累积发生率分别为 0.10 ± 0.02 和 0.03 ± 0.02（P =.017），复发率（±SD）分别为 0.22 ± 0.02 和 0.24 ± 0.04（P =.732）。在接受无关供者移植的受者中，9/10 匹配和 10/10 匹配移植物之间、外周血干细胞和骨髓之间的无事件生存率、总生存率或非复发死亡率无显著差异。无慢性移植物抗宿主病对无事件生存率无影响。同胞来源的骨髓移植的植入更快，与严重感染和肺部并发症发生率较低有关。
高危儿童 ALL 患者造血干细胞移植后的结局不受供者类型的影响。标准化的清髓性预处理产生了低的治疗相关死亡率和有效的白血病控制。
