Germline mutations in GATA2 are associated with an inherited predisposition to bone marrow failure (BMF), myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Hematopoietic stem cell transplantation (HSCT) remains the only curative therapy. However, patients may be at an increased risk for transplant-related toxicity (TRT) and mortality (TRM) due to their underlying disease biology. We performed a retrospective case-control study of pediatric BMF/MDS/AML patients with germline GATA2 mutations, comparing HSCT outcomes to randomly selected patients without germline GATA2 mutations and BMF/MDS (control A) and acute leukemia (control B). The 5-year overall and disease-free survival rates in the GATA2 cohort (65%, 51%) were similar to control A (58%, 49%) and B (45%, 43%) cohorts. In contrast, the 5-year event-free survival rate was significantly lower in the GATA2 cohort (7%±6%, 28%±10% and 33%±8% for GATA2, A, and B, respectively), due to an increased number of unique TRT. Specifically, neurologic toxicities occurred significantly more frequently in GATA2 patients than in the control groups and post-HSCT thrombotic events occurred only in the GATA2 cohort. There was no difference in TRM, infections or graft-versus-host disease (GVHD) across groups. The higher incidence of thrombotic and neurological events specific to GATA2 patients warrants further investigation and has potential treatment ramifications.

中文翻译：

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小儿骨髓衰竭，骨髓增生异常综合症和急性髓系白血病伴和不伴生殖系GATA2突变的小儿异体清髓同种异体干细胞移植结果的比较。

GATA2中的种系突变与遗传性骨髓衰竭（BMF），骨髓增生异常综合症（MDS）和急性髓细胞性白血病（AML）的易感性有关。造血干细胞移植（HSCT）仍然是唯一的治疗方法。但是，由于患者潜在的疾病生物学特性，其与移植相关的毒性（TRT）和死亡率（TRM）的风险可能会增加。我们对具有种系GATA2突变的小儿BMF / MDS / AML患者进行了回顾性病例对照研究，将HSCT结果与随机选择的没有种系GATA2突变和BMF / MDS的患者（对照A）和急性白血病（对照B）进行了比较。GATA2组的5年总体生存率和无病生存率（65％，51％）与对照组A（58％，49％）和B组（45％，43％）相似。相反，由于人数增加，GATA2队列的5年无事件生存率显着降低（GATA2，A和B分别为7％±6％，28％±10％和33％±8％）独特的TRT。具体而言，与对照组相比，GATA2患者的神经毒性发生率更高，HSCT后血栓事件仅在GATA2队列中发生。各组之间的TRM，感染或移植物抗宿主病（GVHD）没有差异。特定于GATA2患者的血栓和神经系统事件发生率较高，值得进一步研究，并可能对治疗产生影响。与对照组相比，GATA2患者发生神经毒性的频率明显更高，HSCT后血栓事件仅发生在GATA2队列中。各组之间的TRM，感染或移植物抗宿主病（GVHD）没有差异。特定于GATA2患者的血栓和神经系统事件发生率较高，值得进一步研究，并可能对治疗产生影响。与对照组相比，GATA2患者发生神经毒性的频率明显更高，HSCT后血栓事件仅发生在GATA2队列中。各组之间的TRM，感染或移植物抗宿主病（GVHD）没有差异。特定于GATA2患者的血栓和神经系统事件发生率较高，值得进一步研究，并可能对治疗产生影响。