Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah University Medical Center, Jerusalem, Israel.
Immunology Division, Garvan Institute of Medical Research, Sydney, Australia.
Pediatr Blood Cancer. 2018 Jun;65(6):e27010. doi: 10.1002/pbc.27010. Epub 2018 Feb 22.
Infantile malignant osteopetrosis (IMO) is an autosomal recessive condition characterized by defective osteoclast activity, with hematopoietic bone marrow transplant being the only available cure. Over the past several years, new conditioning regimes and donor options have emerged, thus extending the possibility of cure to a greater number of patients and improving the outcomes of bone marrow transplant. Here we detail the outcomes of bone marrow transplant in a cohort of 31 patients treated with a combination of fludarabine, treosulphan, thiotepa, and antithymocyte globulin.
Thirty-one patients with IMO who underwent hematopoietic stem cell transplantation with fludarabine, treosulphan, thiotepa, and antithymocyte globulin at our center from 2012 to 2017 are retrospectively reviewed in this study. Twenty-six patients were transplanted from 10/10 matched donors (13 from siblings, 11 from unrelated, and two from extended family donors), four from 9/10 matched unrelated donors, and one from a 9/10 matched family donor.
Overall survival was 100% with a median follow-up of 363 days (range 74-1891). There were 12 cases of acute graft versus host disease (GvHD) (38.7%), no cases of veno-occlusive disease, and eight cases of hypercalcemia (25.8%). Almost 80% of patients suffered viral reactivations with two cases of Epstein-Barr-virus-driven post-transplant lymphoproliferative disease. All cases of GvHD and viral reactivation were successfully treated.
We conclude that transplantation in children with IMO using fludarabine, treosulphan, thiotepa, and antithymocyte globulin is safe and effective and should be performed as early as possible following diagnosis, prior to the development of severe disease sequelae.
婴儿恶性骨硬化症（IMO）是一种常染色体隐性疾病，其特征是破骨细胞活性缺陷，造血干细胞移植是唯一可行的治疗方法。在过去的几年中，新的预处理方案和供者选择已经出现，从而使更多的患者有治愈的可能，并改善了骨髓移植的结果。在这里，我们详细介绍了我们中心 31 名 IMO 患者接受氟达拉滨、硫唑嘌呤、噻替哌和抗胸腺细胞球蛋白联合治疗后进行骨髓移植的结果。
本研究回顾性分析了 2012 年至 2017 年期间在我们中心接受氟达拉滨、硫唑嘌呤、噻替哌和抗胸腺细胞球蛋白造血干细胞移植的 31 例 IMO 患者。26 例患者接受了 10/10 配型相合供者（13 例来自同胞，11 例来自无关供者，2 例来自扩展家族供者）的移植，4 例患者接受了 9/10 配型无关供者的移植，1 例患者接受了 9/10 配型家族供者的移植。
总生存率为 100%，中位随访时间为 363 天（范围 74-1891 天）。急性移植物抗宿主病（GVHD）12 例（38.7%），无静脉闭塞病，高钙血症 8 例（25.8%）。近 80%的患者发生病毒再激活，2 例发生 EBV 驱动的移植后淋巴增殖性疾病。所有 GVHD 和病毒再激活均得到成功治疗。
我们得出结论，IMO 患儿使用氟达拉滨、硫唑嘌呤、噻替哌和抗胸腺细胞球蛋白进行移植是安全有效的，应在确诊后尽早进行，以避免出现严重的疾病后遗症。
