Department of Haematology, Christian Medical College, Vellore, India.
Princess Margaret Hospital, Toronto, ON, Canada.
Bone Marrow Transplant. 2018 Feb;53(2):169-174. doi: 10.1038/bmt.2017.231. Epub 2017 Oct 16.
Mixed chimerism (MC) occurs frequently after allogeneic hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) and may be associated with rejection. We report the outcome of MC in 132 TM patients conditioned with Busulphan/Cyclophosphamide, who had successful engraftment and had ⩾1 year follow-up. Chimerism was first assessed at day +28, then every 3-9 months or more frequently if there was MC. If rejection was suspected, immunosuppression was stopped and donor-lymphocyte infusion (DLI) was given if there was no response. Among 132 patients, aged 7 years (range: 2-24), 46/132 (34.8%) had MC in the first year, 32/46 (69.6%) at day +28 and another 14 (30%) between day +28 and 1 year post HSCT. MC was quantified at level 1 (residual host chimerism (RHC) <10%) in 20 (43.5%), level II (RHC 10-25%) in 14 (30.4%) and level III (RHC >25%) in 12 (26.1%). On tapering immunosuppression, 15 (32.6%) developed acute GvHD and 8 (17.4%) had chronic GvHD with reversal to complete chimerism (CC). DLI was administered to 5/46 (10.9%), 1 evolved to CC but 4 rejected the graft. At median follow-up of 60 months (range: 16-172), 20/46 (43.5%) had CC, 18/46 (39.1%) had persistent MC with hemoglobin of 11.5 g/dL (range: 8.4-13.6), whereas 8 (17.4%) rejected the graft. Close monitoring and early intervention is needed with increasing recipient chimerism. Novel strategies are required for preventing graft rejection.
混合嵌合体（MC）在重型地中海贫血（TM）患者接受异基因造血干细胞移植（HSCT）后经常发生，并且可能与排斥反应有关。我们报告了 132 例接受白消安/环磷酰胺预处理的 TM 患者的 MC 结果，这些患者均成功植入，并随访 ⩾1 年。嵌合体首先在移植后第 28 天评估，然后每 3-9 个月或更频繁地进行评估，如果存在 MC。如果怀疑发生排斥反应，则停止免疫抑制，并在没有反应的情况下给予供体淋巴细胞输注（DLI）。在 132 例患者中，年龄为 7 岁（范围：2-24 岁），46/132（34.8%）在第 1 年内出现 MC，其中 32/46（69.6%）在移植后第 28 天，另外 14 例（30%）在移植后第 28 天至 1 年内出现 MC。MC 定量为 1 级（残留宿主嵌合体（RHC）<10%）的有 20 例（43.5%），定量为 2 级（RHC 10-25%）的有 14 例（30.4%），定量为 3 级（RHC>25%）的有 12 例（26.1%）。在减少免疫抑制的过程中，15 例（32.6%）发生急性移植物抗宿主病，8 例（17.4%）发生慢性移植物抗宿主病，均转为完全嵌合体（CC）。对 46 例中的 5 例（10.9%）给予 DLI，其中 1 例转为 CC，但 4 例排斥移植物。中位随访 60 个月（范围：16-172 个月）时，20/46（43.5%）为 CC，18/46（39.1%）持续存在 MC，血红蛋白为 11.5g/dL（范围：8.4-13.6），8 例（17.4%）排斥移植物。随着受体嵌合体的增加，需要密切监测和早期干预。需要新的策略来预防移植物排斥反应。
