Department of Haematology, Christian Medical College and Hospital, Vellore, India.
Department of Haematology, Christian Medical College and Hospital, Vellore, India.
Biol Blood Marrow Transplant. 2018 Jan;24(1):103-108. doi: 10.1016/j.bbmt.2017.10.012. Epub 2017 Oct 12.
Graft rejection (GR) after allogeneic stem cell transplantation (allo-SCT) occurs in 10% to 20% of patients with β-thalassemia major (TM). There are limited data on the clinical profile and long-term outcome of patients who have had a GR. We undertook a retrospective analysis of patients who had a graft failure after allo-SCT for TM at our center. From October 1991 to June 2016, 55 of 506 patients (11%) transplanted for TM had a graft failure. An additional 7 patients with graft failure after allo-SCT done at other centers were referred to us for a second transplant. The median age was 8 years (range, 1 to 19), and there were 38 males (61.2%). Thirty-two patients (52.4%) were primary graft failures (15 with aplasia and 17 with autologous recovery) and 30 (47.6%) were secondary graft failures (5 with aplasia and 25 with autologous recovery). On conventional risk stratification 40 patients (64.5%) were class III. Seventeen patients (53.12%) with primary graft failure and 16 (53.3%) with secondary graft failure did not receive a second transplant. Twenty-nine patients (46%) with GR underwent a second allo-SCT. With the exception of 1 patient (first allo-SCT with an unrelated cord blood product), the donor for the second transplant was the same as the first transplant. Conditioning regimen for the second SCT was busulfan-based myeloablative (MAC) in 7 patients (24%), treosulfan-based MAC in 12 patients (41.3%), and the remaining received non-MAC regimens in view of pancytopenia and perceived inability to tolerate MAC. None of the patients conditioned with a treosulfan-based regimen had a GR, although 1 patient died with complications secondary to chronic graft-versus-host disease. Of the remaining 17 patients, 10 died after the second GR and 3 of regimen-related toxicity. Four are alive, of which 1 has recurrent TM and the rest are well and transfusion independent at 55, 80, and 204 months, respectively, from second transplant (all busulfan-based MAC). On a univariate analysis a nontreosulfan-based conditioning regimen and time from GR to second transplant of <1 year was significantly associated with an adverse impact. However, on a multivariate analysis only a nontreosulfan-based regimen was associated with a significant adverse impact on event-free survival (HR, 11.5; 95% CI, 1.13 to 116.4; P = .039). In conclusion, there has been a significant improvement in clinical outcomes in our experience with the use of a treosulfan-based reduced-toxicity MAC regimen for second allo-SCT for TM. It would be reasonable, where feasible, to defer the second transplant by a year after the first GR.
同种异体干细胞移植（allo-SCT）后移植物排斥（GR）发生在 10%至 20%的β-地中海贫血重型（TM）患者中。关于发生 GR 的患者的临床特征和长期结果的数据有限。我们对我院因 TM 接受 allo-SCT 后发生移植物失败的患者进行了回顾性分析。1991 年 10 月至 2016 年 6 月，506 例接受 TM 移植的患者中有 55 例（11%）发生移植物失败。另外 7 例在其他中心接受 allo-SCT 后发生移植物失败的患者被转诊至我们中心进行二次移植。中位年龄为 8 岁（范围，1 至 19），其中男性 38 例（61.2%）。32 例（52.4%）为原发性移植物失败（15 例为发育不全，17 例为自身恢复），30 例（47.6%）为继发性移植物失败（5 例为发育不全，25 例为自身恢复）。在常规风险分层中，40 例患者（64.5%）为 III 级。17 例（53.12%）原发性移植物失败和 16 例（53.3%）继发性移植物失败的患者未接受二次移植。29 例（46%）GR 患者接受了第二次 allo-SCT。除 1 例患者（首次 allo-SCT 使用无关脐带血产品）外，第二次移植的供者与第一次相同。第二次 SCT 的预处理方案为 7 例（24%）采用基于白消安的清髓性 MAC，12 例（41.3%）采用基于三氟尿苷的 MAC，其余患者因全血细胞减少和认为不能耐受 MAC 而接受非 MAC 方案。在接受三氟尿苷方案预处理的患者中，没有发生 GR，但 1 例患者死于慢性移植物抗宿主病的并发症。在其余 17 例患者中，10 例在第二次 GR 后死亡，3 例死于与方案相关的毒性。4 例存活，其中 1 例复发 TM，其余 3 例分别在第二次移植后 55、80 和 204 个月时无输血且情况良好（均采用基于白消安的 MAC）。单因素分析显示，非三氟尿苷预处理方案和 GR 至第二次移植的时间<1 年与不良影响显著相关。然而，多因素分析仅显示非三氟尿苷方案与第二次 allo-SCT 后无事件生存的不良影响显著相关（HR，11.5；95%CI，1.13 至 116.4；P=0.039）。总之，在使用基于三氟尿苷的降低毒性 MAC 方案进行第二次 allo-SCT 治疗 TM 方面，我们的经验显示出临床结局的显著改善。在第一次 GR 后，推迟一年进行第二次移植是合理的。
