Department of Pediatrics, City of Hope, Duarte, CA.
Southern California Kaiser Permanente Medical Group, Los Angeles, CA.
Biol Blood Marrow Transplant. 2018 Jan;24(1):185-189. doi: 10.1016/j.bbmt.2017.08.039. Epub 2017 Sep 20.
Allogeneic stem cell transplantation (HCT) is curative in patients with severe sickle cell disease (SCD), but a significant number of patients lack an HLA-identical sibling or matched unrelated donor. Mismatched related (haploidentical) HCT with post-transplant cyclophosphamide (PTCY) allows expansion of the donor pool but is complicated by high rates of graft failure. In this report we describe a favorable haploidentical HCT approach in a limited cohort of SCD patients with significant comorbidities. To reduce the risk of graft failure we administered the conditioning regimen of rabbit antithymocyte globulin, busulfan, and fludarabine preceded with 2 courses of pretransplant immunosuppressive therapy (PTIS) with fludarabine and dexamethasone. Graft-versus-host disease (GVHD) prophylaxis consisted of PTCY on days +3 and +4 followed by tacrolimus and mycophenolate mofetil starting on day +5. Four patients (ages 13, 19, 19, and 23 years) received T cell-replete haploidentical stem cell infusion. All patients engrafted with 99.9% to 100% donor chimerism, and all patients continued with stable engraftment at the last follow-up (5 to 11 months post-transplant). Time to neutrophil engraftment was 14 to 26 days. Two patients had high levels of donor-specific anti-HLA antibodies, which required the implementation of an antibody management protocol. This facilitated neutrophil engraftment on day +16 and day +26, respectively. One patient developed grade I acute GVHD, which resolved. Three patients developed mild, limited skin GVHD that responded to conventional immunosuppressive therapy. Human herpesvirus-6 viremia was detected in 3 patients but resolved without treatment. One patient developed asymptomatic cytomegalovirus viremia that responded appropriately to standard therapy with ganciclovir. The prompt, stable engraftment and low toxicity in the post-transplant period makes PTIS with haploidentical transplant a promising option for patients with SCD.
同种异体干细胞移植（HCT）可治愈严重镰状细胞病（SCD）患者，但相当数量的患者缺乏 HLA 完全匹配的同胞或无关供体。使用移植后环磷酰胺（PTCY）的不合 HLA 相关（半相合）HCT 可扩大供体池，但由于移植物失败率高而变得复杂。在本报告中，我们描述了一种有利的半相合 HCT 方法，该方法适用于患有严重合并症的有限 SCD 患者队列。为了降低移植物失败的风险，我们给予了兔抗胸腺细胞球蛋白、白消安和氟达拉滨的预处理方案，并在移植前用氟达拉滨和地塞米松进行了 2 个疗程的免疫抑制治疗（PTIS）。移植物抗宿主病（GVHD）预防包括在第 3 天和第 4 天给予 PTCY，然后在第 5 天开始使用他克莫司和霉酚酸酯。4 名患者（年龄 13、19、19 和 23 岁）接受了 T 细胞充足的半相合干细胞输注。所有患者均植入了 99.9%至 100%的供体嵌合体，并且所有患者在最后一次随访（移植后 5 至 11 个月）时继续稳定植入。中性粒细胞植入时间为 14 至 26 天。2 名患者有高水平的供体特异性抗 HLA 抗体，这需要实施抗体管理方案。这分别在第 16 天和第 26 天促进了中性粒细胞植入。1 名患者发生 1 级急性 GVHD，随后缓解。3 名患者发生轻度、局限性皮肤 GVHD，对常规免疫抑制治疗有反应。3 名患者检测到人类疱疹病毒 6 血症，但未经治疗即缓解。1 名患者发生无症状巨细胞病毒血症，用更昔洛韦标准治疗后适当反应。移植后迅速、稳定的植入和低毒性使得半相合移植与 PTIS 一起成为 SCD 患者的一种有前途的选择。
