Dmitriy Rogachev National Center for Pediatric Hematology, Oncology and Immunology, Department of Immunology, 1, Samory Mashela str, 117997, Moscow, Russia.
Dmitriy Rogachev National Center for Pediatric Hematology, Oncology and Immunology, Department of Hematopoietic Stem Cell Transplantation, 1, Samory Mashela str, 117997, Moscow, Russia.
Orphanet J Rare Dis. 2019 May 3;14(1):97. doi: 10.1186/s13023-019-1073-x.
Mosaic variegated aneuploidy (MVA) syndrome is a chromosomal instability disorder that leads to aneuploidies of different chromosomes in various tissues. Type 1 MVA (MVA1) is caused by mutations in the budding uninhibited by benzimidazoles 1 homolog beta (BUB1B) gene. The main clinical features of MVA1 syndrome are growth and mental retardation, central nervous system anomalies, microcephaly, and predisposition to cancers. There have been no reports of hematopoietic stem cell transplantation (HSCT) in MVA patients.
We report an 11-year old boy diagnosed with MVA1 syndrome. The BUB1B gene mutations c.498_505delAAACTTTA and c.1288 + 5G > A were detected using the next generation sequencing (NGS) method. The patient presented with cytopenia soon after birth, but remained stable until 9 years of age, when he developed myelodysplastic syndrome associated with monosomy of chromosome 7. Due to severe dependence on blood transfusions, a TCRαβ+/CD19+ depleted HSCT was performed from a matched unrelated donor (MUD) using a treosulfan-based reduced intensity conditioning (RIC) regimen. The engraftment occurred, and no severe toxicity was observed soon after the HSCT, but on day + 47, graft rejection was detected. It was followed by prolonged pancytopenia and sepsis with multi-organ Enterococcus faecium infection, which led to the patient's death on day + 156 after HSCT.
In conclusion, we demonstrate that RIC HSCT with TCRαβ+/CD19+ depletion was well tolerated and resulted in complete hematologic recovery in our MVA1 patient, but, unfortunately, it was followed by rapid graft rejection. This fact needs to be taken into consideration for HSCT in other MVA patients.
镶嵌性杂合性非整倍体（MVA）综合征是一种染色体不稳定性疾病，可导致不同组织中不同染色体的非整倍体。1 型 MVA（MVA1）是由芽殖无抑制物 1 同源物β（BUB1B）基因突变引起的。MVA1 综合征的主要临床特征是生长和智力发育迟缓、中枢神经系统异常、小头症和癌症易感性。目前尚无 MVA 患者造血干细胞移植（HSCT）的报道。
我们报告了一例 11 岁男孩，被诊断为 MVA1 综合征。使用下一代测序（NGS）方法检测到 BUB1B 基因突变 c.498_505delAAACTTTA 和 c.1288 + 5G > A。该患者出生后不久即出现细胞减少症，但一直保持稳定，直到 9 岁时发展为伴有 7 号染色体单体性的骨髓增生异常综合征。由于严重依赖输血，我们从匹配的无关供体（MUD）进行了 TCRαβ+/CD19+ 耗尽的 HSCT，使用基于三氟胸苷的减低强度预处理（RIC）方案。移植后发生嵌合，HSCT 后不久未观察到严重毒性，但在+ 47 天，发现移植物排斥。随后出现长时间全血细胞减少症和脓毒症，伴有多器官粪肠球菌感染，导致患者在 HSCT 后+ 156 天死亡。
总之，我们证明了 TCRαβ+/CD19+ 耗尽的 RIC HSCT 在我们的 MVA1 患者中耐受良好，导致完全血液学恢复，但不幸的是，随后发生快速移植物排斥。这一事实需要在其他 MVA 患者的 HSCT 中加以考虑。
