Hematopoietic stem cell transplantation in a patient with type 1 mosaic variegated aneuploidy syndrome | Orphanet Journal of Rare Diseases | Full Text

Hematopoietic stem cell transplantation in a patient with type 1 mosaic variegated aneuploidy syndrome | Orphanet Journal of Rare Diseases | Full Text

Orphanet Journal of Rare Diseases

Hematopoietic stem cell transplantation in a patient with type 1 mosaic variegated aneuploidy syndrome

• Alexandra LaberkoEmail authorView ORCID ID profile,
• Dmitry BalashovView ORCID ID profile,
• Elena DeripapaView ORCID ID profile,
• Olga SoldatkinaView ORCID ID profile,
• Elena RaikinaView ORCID ID profile,
• Alexei MaschanView ORCID ID profile,
• Galina NovichkovaView ORCID ID profile and
• Anna ShcherbinaView ORCID ID profile

Orphanet Journal of Rare Diseases201914:97

https://doi.org/10.1186/s13023-019-1073-x

©  The Author(s). 2019

• Received: 24 January 2019
• Accepted: 17 April 2019
• Published: 3 May 2019

Abstract

Background

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.

Results

We report an 11-year old boy diagnosed with MVA1 syndrome. The BUB1Bgene 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.

Conclusions

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.

Keywords

• Mosaic variegated aneuploidy syndrome
• BUB1B gene.
• Hematopoietic stem cell transplantation.
• TCRαβ+/CD19+ graft depletion.