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与来自人类白细胞抗原匹配的相关或无关供体的异基因造血干细胞移植相比,单倍体相合T细胞充足移植联合移植后环磷酰胺用于60岁及以上患者的治疗

Haploidentical T Cell-Replete Transplantation with Post-Transplantation Cyclophosphamide for Patients in or above the Sixth Decade of Age Compared with Allogeneic Hematopoietic Stem Cell Transplantation from an Human Leukocyte Antigen-Matched Related or Unrelated Donor.

作者信息

Blaise Didier, Fürst Sabine, Crocchiolo Roberto, El-Cheikh Jean, Granata Angela, Harbi Samia, Bouabdallah Reda, Devillier Raynier, Bramanti Stephania, Lemarie Claude, Picard Christophe, Chabannon Christian, Weiller Pierre-Jean, Faucher Catherine, Mohty Bilal, Vey Norbert, Castagna Luca

机构信息

Transplant and Cellular Therapy Unit, Institut Paoli Calmettes, Marseille, France; Hematology Department, Institut Paoli Calmettes, Marseille, France; Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France; Aix-Marseille University (AMU), Marseille, France.

Transplant and Cellular Therapy Unit, Institut Paoli Calmettes, Marseille, France; Hematology Department, Institut Paoli Calmettes, Marseille, France.

出版信息

Biol Blood Marrow Transplant. 2016 Jan;22(1):119-24. doi: 10.1016/j.bbmt.2015.08.029. Epub 2015 Sep 1.

Abstract

It has recently been shown that a T cell-replete allogeneic (allo) hematopoietic stem cell transplantation (HSCT) from a haploidentical donor (haplo-ID) could be a valid treatment for hematological malignancies. However, little data exist concerning older populations. We provided transplantation to 31 patients over the age of 55 years from a haplo-ID and compared their outcomes with patients of the same ages who underwent transplantation from a matched related (MRD) or an unrelated donor (UD). All 3 groups were comparable, except for their conditioning. Patients in haplo-ID group received 2 days of post-transplantation high-dose cyclophosphamide followed by cyclosporine A and mycophenolate mofetil, whereas patients in other groups received pretransplantation antithymocyte globulin, cyclosporine A, and additional mycophenolate mofetil in case of 1-antigen mismatch. All patients but 1 in the haplo-ID group engrafted. The incidence of grades 2 to 4 acute graft-versus-host disease (GVHD) was not statistically different between recipients from haplo-ID (cumulative incidence, 23%) and MRD (cumulative incidence, 21%) transplantations but it was lower than after UD HSCT (cumulative incidence, 44%). No patient in the haplo-ID group developed severe chronic GVHD, compared with cumulative incidences of 16% and 14% after MRD (P = .02) and UD (P = .03) grafts, respectively. The cumulative incidences of relapse were similar in the 3 groups, whereas nonrelapse mortality after UD HSCT was 3-fold higher than after haplo-ID or MRD HSCT. Overall, 2-year overall survival (70%), progression-free survival (67%), and progression and severe chronic GVHD-free survival (67%) probabilities after haplo-ID did not statistically differ from MRD transplantation (78%, 64%, and 51%, respectively), although they were higher than after UD transplantation (51% [P = .08], 38% [P = .02], and 31% [P = .007]). We conclude that T cell-replete haplo-ID HSCT followed by post-transplantation high-dose- cyclophosphamide in patients over 55 years is associated with promising results, similar to MRD HSCT, and is deserving prospective evaluation.

摘要

最近研究表明,来自单倍体相合供者(haplo-ID)的富含T细胞的异基因造血干细胞移植(HSCT)可能是治疗血液系统恶性肿瘤的一种有效方法。然而,关于老年人群的数据很少。我们为31名55岁以上的患者进行了haplo-ID造血干细胞移植,并将他们的结果与接受匹配相关供者(MRD)或无关供者(UD)移植的同龄患者进行了比较。除预处理方案外,所有3组具有可比性。haplo-ID组患者在移植后接受2天高剂量环磷酰胺治疗,随后使用环孢素A和霉酚酸酯,而其他组患者在移植前接受抗胸腺细胞球蛋白、环孢素A治疗,在出现1个抗原不匹配的情况下额外使用霉酚酸酯。haplo-ID组除1名患者外所有患者均实现造血重建。haplo-ID移植受者(累积发生率为23%)和MRD移植受者(累积发生率为21%)之间2至4级急性移植物抗宿主病(GVHD)的发生率无统计学差异,但低于UD HSCT后(累积发生率为44%)。haplo-ID组没有患者发生严重慢性GVHD,而MRD移植(P = 0.02)和UD移植(P = 0.03)后累积发生率分别为16%和14%。3组复发的累积发生率相似,而UD HSCT后的非复发死亡率比haplo-ID或MRD HSCT高3倍。总体而言,haplo-ID移植后2年总生存率(70%)、无进展生存率(67%)以及无进展和严重慢性GVHD生存率(67%)与MRD移植(分别为78%、64%和51%)相比无统计学差异,尽管高于UD移植(51% [P = 0.08]、38% [P = 0.02]和31% [P = 0.007])。我们得出结论,55岁以上患者接受富含T细胞的haplo-ID HSCT并在移植后使用高剂量环磷酰胺,可取得与MRD HSCT相似的良好结果,值得进行前瞻性评估。

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