Lindemans Caroline A, Te Boome Liane C J, Admiraal Rick, Jol-van der Zijde Els C, Wensing Anne M, Versluijs A Birgitta, Bierings Marc B, Kuball Jürgen, Boelens Jaap J
Pediatric Blood and Bone Marrow Program, University Medical Center Utrecht, The Netherlands.
Department of Hematology, University Medical Center Utrecht, The Netherlands; Tumorimmunology, Lab Translational Immunology, University Medical Center Utrecht, The Netherlands.
Biol Blood Marrow Transplant. 2015 Oct;21(10):1839-45. doi: 10.1016/j.bbmt.2015.06.001. Epub 2015 Jun 26.
In haploidentical (haplo)-cord blood (CB) transplantations, early haplo donor engraftment serves as a myeloid bridge to sustainable CB engraftment and is associated with early neutrophil recovery. The conditioning regimens as published for haplo-cord protocols usually contain serotherapy, such as rabbit antithymocyte globulin (ATG) (Thymoglobulin, Genzyme, Cambridge, MA). However, reducing or omitting serotherapy is an important strategy to improve early immune reconstitution after transplantation. The need for serotherapy in successful haplo-cord transplantation, defined as having a haplo-derived myeloid bridge to CB engraftment, has not been investigated before. Two consecutive cohorts of patients underwent transplantation with haplo-CB. The first group underwent transplantation with haplo-CB for active infection and/or an underlying condition with expected difficult engraftment without a conventional donor available. They received a single unit (s) CB and haplo donor cells (CD34(+) selected, 5 × 10(6) CD34(+)/kg). The second cohort included patients with poor-risk malignancies, not eligible for other treatment protocols. They received a sCB and haplo donor cells (CD19/αβTCR-depleted; 5 × 10(6) CD34(+)/kg). Retrospectively in both cohorts, active ATG (Thymoglobulin) levels were measured and post-hematopoietic cell transplantation area under the curve (AUC) was calculated. The influence of ATG exposure for having a successful haplo-myeloid bridge (early haplo donor engraftment before CB engraftment and no secondary neutropenia) and transplantation-related mortality (TRM) were analyzed as primary endpoints. Twenty patients were included (16 in the first cohort and 4 in the second cohort). In 58% of evaluable patients, there was no successful haplo-derived myeloid bridge to CB engraftment, for which a low post-transplantation ATG exposure appeared to be a predictor (P <.001). TRM in the unsuccessful haplo-bridge group was 70% ± 16% versus 12% ± 12% in the successful haplo-bridge group (P = .012). In conclusion, sufficient in vivo T depletion with ATG is required for a successful haplo-myeloid bridge to CB engraftment.
在单倍体相合的脐带血移植中，早期单倍体供者植入作为通向可持续脐带血植入的髓系桥梁，并与早期中性粒细胞恢复相关。已公布的单倍体 - 脐带血方案的预处理方案通常包含血清疗法，如兔抗胸腺细胞球蛋白（ATG）（即胸腺球蛋白，健赞公司，马萨诸塞州剑桥市）。然而，减少或省略血清疗法是改善移植后早期免疫重建的一项重要策略。在成功的单倍体 - 脐带血移植（定义为具有通向脐带血植入的单倍体来源的髓系桥梁）中血清疗法的必要性此前尚未得到研究。连续两组患者接受了单倍体 - 脐带血移植。第一组患者因活动性感染和 / 或存在预期植入困难且无常规供者可用的基础疾病而接受单倍体 - 脐带血移植。他们接受了单个单位的脐带血和单倍体供者细胞（经CD34(+)选择，5×10⁶个CD34(+)/kg）。第二组包括患有高危恶性肿瘤且不符合其他治疗方案的患者。他们接受了单个单位的脐带血和单倍体供者细胞（去除CD19/αβTCR；5×10⁶个CD34(+)/kg）。对两组患者进行回顾性研究，检测了活性ATG（胸腺球蛋白）水平并计算了造血细胞移植后曲线下面积（AUC）。将ATG暴露对形成成功的单倍体 - 髓系桥梁（在脐带血植入前早期单倍体供者植入且无继发性中性粒细胞减少）和移植相关死亡率（TRM）的影响作为主要终点进行分析。共纳入20例患者（第一组16例，第二组4例）。在58%的可评估患者中，不存在通向脐带血植入的成功的单倍体来源的髓系桥梁，对于这部分患者，移植后低ATG暴露似乎是一个预测因素（P <.001）。未成功形成单倍体桥梁组的TRM为70%±16%，而成功形成单倍体桥梁组为12%±12%（P =.012）。总之，为了成功形成通向脐带血植入的单倍体 - 髓系桥梁，需要用ATG在体内充分清除T细胞。
