Clinica Pediatrica, Università degli Studi di Milano Bicocca, Fondazione Monza e Brianza per il Bambino e la sua Mamma, Ospedale San Gerardo, Monza, Italy.
Hemato-Immunology Department, Robert-Debre Hospital, APHP and Paris-Diderot University, Paris, France.
Biol Blood Marrow Transplant. 2019 Nov;25(11):2197-2210. doi: 10.1016/j.bbmt.2019.07.011. Epub 2019 Jul 15.
Eligibility criteria for hematopoietic stem cell transplantation (HSCT) in acute lymphoblastic leukemia (ALL) vary according to disease characteristics, response to treatment, and type of available donor. As the risk profile of the patient worsens, a wider degree of HLA mismatching is considered acceptable. A total of 138 children and adolescents who underwent HSCT from HLA-identical sibling donors (MSDs) and 210 who underwent HSCT from matched donors (MDs) (median age, 9 years; 68% male) in 10 countries were enrolled in the International-BFM ALL SCT 2007 prospective study to assess the impact of donor type in HSCT for pediatric ALL. The 4-year event-free survival (65 ± 5% vs 61 ± 4%; P = .287), overall survival (72 ± 4% versus 68 ± 4%; P = .235), cumulative incidence of relapse (24 ± 4% versus 25 ± 3%; P = .658) and nonrelapse mortality (10 ± 3% versus 14 ± 3%; P = .212) were not significantly different between MSD and MD graft recipients. The risk of extensive chronic (cGVHD) was lower in MD graft recipients than in MSD graft recipients (hazard ratio [HR], .38; P = .002), and the risks of severe acute GVHD (aGVHD) and cGVHD were higher in peripheral blood stem cell graft recipients than in bone marrow graft recipients (HR, 2.06; P = .026). Compared with the absence of aGVHD, grade I-II aGVHD was associated with a lower risk of graft failure (HR, .63; P = .042) and grade III-IV aGVHD was associated with a higher risk of graft failure (HR, 1.85; P = .020) and nonleukemic death (HR, 8.76; P < .0001), despite a lower risk of relapse (HR, .32; P = .021). Compared with the absence of cGVHD, extensive cGVHD was associated with a higher risk of nonleukemic death (HR, 8.12; P < .0001). Because the outcomes of transplantation from a matched donor were not inferior to those of transplantation from an HLA-identical sibling, eligibility criteria for transplantation might be reviewed in pediatric ALL and possibly in other malignancies as well. Bone marrow should be the preferred stem cell source, and the addition of MTX should be considered in MSD graft recipients.
造血干细胞移植（HSCT）在急性淋巴细胞白血病（ALL）中的入选标准因疾病特征、治疗反应和可用供体类型而异。随着患者风险状况的恶化，可接受的 HLA 错配程度也会增加。共有 138 名来自 HLA 同型兄弟姐妹供体（MSD）的儿童和青少年以及 210 名来自匹配供体（MD）的儿童和青少年（中位年龄 9 岁；68%为男性）在 10 个国家入组国际-BFM ALL SCT 2007 前瞻性研究，以评估供体类型对儿科 ALL 中 HSCT 的影响。4 年无事件生存率（65±5%与 61±4%；P=0.287）、总生存率（72±4%与 68±4%；P=0.235）、复发累积发生率（24±4%与 25±3%；P=0.658）和非复发死亡率（10±3%与 14±3%；P=0.212）在 MSD 和 MD 移植物受者之间无显著差异。MD 移植物受者的广泛慢性移植物抗宿主病（cGVHD）风险低于 MSD 移植物受者（风险比 [HR]，0.38；P=0.002），而外周血干细胞移植物受者的严重急性移植物抗宿主病（aGVHD）和 cGVHD 风险高于骨髓移植物受者（HR，2.06；P=0.026）。与无 aGVHD 相比，I-II 级 aGVHD 与较低的移植物失败风险相关（HR，0.63；P=0.042），而 III-IV 级 aGVHD 与较高的移植物失败风险相关（HR，1.85；P=0.020）和非白血病死亡（HR，8.76；P<.0001），尽管复发风险较低（HR，0.32；P=0.021）。与无 cGVHD 相比，广泛的 cGVHD 与非白血病死亡风险增加相关（HR，8.12；P<.0001）。由于来自匹配供体的移植结果并不劣于来自 HLA 同型兄弟姐妹的移植结果，因此可能需要重新审查儿科 ALL 以及其他恶性肿瘤的移植入选标准。骨髓应作为首选的干细胞来源，并且应考虑在 MSD 移植物受者中添加 MTX。
