Gaucher Clinic, Shaare Zedek Medical Center, affiliated with Hebrew-University Medical School, Jerusalem, Israel.
Academic Medical Centre, Amsterdam, Netherlands.
J Inherit Metab Dis. 2018 Nov;41(6):1259-1265. doi: 10.1007/s10545-018-0195-y. Epub 2018 Jul 31.
Preliminary data suggest a positive effect of taliglucerase alfa on the bone marrow infiltration of Gaucher cells. In this investigator-initiated study, we report the impact of taliglucerase alfa on the bone marrow fat fraction (FF) in 26 patients assessed by quantitative chemical shift imaging (QCSI). Of 15 treatment-naïve patients (median age 48 [range 24-68] years), eight had baseline FF ≤ 0.3, six of those with a FF ≤ 0.23 ('bone at risk'). All significantly improved from a median baseline FF of 0.24 (0.15-0.32) to 1st year FF of 0.37 (0.25-0.54) and 2nd year FF of 0.42 (0.27-0.59) (p = 0.01). Among the 11 'switch-over' patients (median age 42 [range 33-69] years; median imiglucerase exposure 8 [range 1-17] years), eight had baseline FF ≤ 0.3, five of those with FF < 0.23. All, but one, significantly improved from a median baseline FF of 0.17 (0.08-0.28) to 1st year FF of 0.3 (0.05-0.34) and 2nd year FF of 0.34 (0.08-0.44) (p = 0.03). Two elderly female patients (age 43 and 58 years, with 17 years imiglucerase exposure) who remained at the same enzyme replacement therapy dose, increased from baseline FF of 0.13 and 0.19 to 0.26 at 1 year. Although the number of observations is small, we hypothesize that switching to taliglucerase may result in an improved bone marrow response. A larger study is needed to assess the early benefit of taliglucerase alfa in adult patients with type 1 Gaucher disease on the bone marrow compartment.
初步数据表明,taliglucerase alfa 对戈谢细胞的骨髓浸润有积极影响。在这项由研究者发起的研究中,我们报告了 taliglucerase alfa 对 26 例患者骨髓脂肪分数(FF)的影响,这些患者通过定量化学位移成像(QCSI)进行评估。在 15 例初治患者中(中位年龄 48 岁[范围 24-68 岁]),8 例基线 FF≤0.3,其中 6 例基线 FF≤0.23(“有风险的骨骼”)。所有患者的骨髓 FF 均显著改善,从中位基线的 0.24(0.15-0.32)分别改善至第 1 年的 0.37(0.25-0.54)和第 2 年的 0.42(0.27-0.59)(p=0.01)。在 11 例“转换”患者中(中位年龄 42 岁[范围 33-69 岁];中位 imiglucerase 暴露时间 8 年[范围 1-17 年]),8 例基线 FF≤0.3,其中 5 例基线 FF<0.23。所有患者(除 1 例外)的骨髓 FF 均显著改善,从中位基线的 0.17(0.08-0.28)分别改善至第 1 年的 0.3(0.05-0.34)和第 2 年的 0.34(0.08-0.44)(p=0.03)。两名年龄较大的女性患者(43 岁和 58 岁,imiglucerase 暴露时间分别为 17 年),维持相同的酶替代治疗剂量,FF 从基线的 0.13 和 0.19 分别增加至第 1 年的 0.26。尽管观察例数较少,但我们假设转换为 taliglucerase 可能会导致骨髓反应得到改善。需要更大规模的研究来评估 taliglucerase alfa 在 1 型戈谢病成年患者骨髓中的早期疗效。