Purpose

Allogeneic bone marrow transplantation (alloBMT) is the only cure for many primary immune deficiency disorders (PIDD), primary immune regulatory disorders (PIRD), and inherited bone marrow failure syndromes (IBMFS).

Methods

We report the results of 25 patients who underwent alloBMT using reduced intensity conditioning (RIC), alternative donors, and post-transplantation cyclophosphamide (PTCy). In an attempt to reduce regimen-related toxicities, we removed low-dose TBI from the prep and added mycophenolate mofetil and tacrolimus for graft-versus-host disease (GVHD) prophylaxis for all donor types in the latter 14 patients. Donors were haploidentical related (n = 14), matched unrelated (n = 9), or mismatched unrelated (n = 2). The median age was 9 years (range 5 months–21 years).

Results

With a median follow-up of 26 months (range 7 months–9 years), the 2-year overall survival is 92%. There were two deaths, one from infection, and one from complications after a second myeloablative BMT. Three patients developed secondary graft failure, one at 2 years and two at >3 years, successfully treated with CD34 cell boost in one or second BMT in two. The remaining 20 patients have full or stable mixed donor chimerism and are disease-free. The incidence of mixed chimerism is increased since removing TBI from the prep. The 6-month cumulative incidence of grade II acute GVHD is 17%, with no grade III–IV. The 1-year cumulative incidence of chronic GVHD is 14%, with severe of 5%.

Conclusion

This alloBMT platform using alternative donors, RIC, and PTCy is associated with excellent rates of engraftment and low rates of GVHD and non-relapse mortality, and offers a curative option for patients with PIDD, PIRD, and IBMFS.

Trial registration

ClinicalTrials.gov Identifier: NCT04232085

中文翻译：

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移植后环磷酰胺降低骨髓移植强度治疗儿科遗传性免疫缺陷和骨髓衰竭综合征

目的

异基因骨髓移植 (alloBMT) 是许多原发性免疫缺陷疾病 (PIDD)、原发性免疫调节疾病 (PIRD) 和遗传性骨髓衰竭综合征 (IBMFS) 的唯一治疗方法。

方法

我们报告了使用降低强度调节 (RIC)、替代供体和移植后环磷酰胺 (PTCy) 接受 alloBMT 的 25 名患者的结果。为了减少与治疗方案相关的毒性，我们从准备中去除了低剂量 TBI，并添加了霉酚酸酯和他克莫司，用于对后 14 名患者的所有供体类型进行移植物抗宿主病 (GVHD) 预防。供体是单倍体相关的 ( n  = 14)、匹配的无关 ( n  = 9) 或不匹配的无关 ( n  = 2)。中位年龄为 9 岁（范围 5 个月至 21 岁）。

结果

中位随访 26 个月（范围 7 个月至 9 年），2 年总生存率为 92%。有 2 人死亡，1 人死于感染，1 人死于第二次清髓性 BMT 后的并发症。三名患者出现继发性移植失败，一名在 2 年时，两名在 >3 年时，成功地在一次或两次 BMT 中使用 CD34 细胞增强治疗。其余 20 名患者具有完全或稳定的混合供体嵌合体，并且没有疾病。由于从准备中去除 TBI，混合嵌合的发生率增加。II 级急性 GVHD 的 6 个月累积发生率为 17%，无 III-IV 级。慢性 GVHD 1 年累积发病率为 14%，重度为 5%。

结论

这个使用替代供体、RIC 和 PTCy 的 alloBMT 平台与出色的植入率、低 GVHD 率和非复发死亡率相关，并为 PIDD、PIRD 和 IBMFS 患者提供治疗选择。

试用注册

ClinicalTrials.gov 标识符：NCT04232085