Successful Unrelated Bone Marrow Transplantation for Three patients with Amegakaryocytic Thrombocytopenia with Radio-Ulnar Synostosis (CTRUS) in Japan

Amegakaryocytic thrombocytopenia with radio-ulnar synostosis (CTRUS) is a rare inherited bone marrow failure syndrome that has the potential to progress to pancytopenia that behaves like TAR.The diagnosis of CTRUS is made later when pronation-supination of the forearm is discovered to be restricted. Hox 11a was reported to be abnormal in the initial cases but at least 1 other case did not have this abnormality. Hematopoietic stem-cell transplantation (HSCT) is presently the only curative treatment approach. We used a reduced intensity transplantation regimen in CTRUS patient with aplastic anemia.We reported two cases of CTRUS who underwent successful unrelated bone marrow transplantation.

Conditioning regimen consisted of Flu, ATG, CY, and TLI (300cGy). For GVHD prophylaxis, all received FK506 and short course MTX. The number of transplanted nucleated cells were 6.35, 6.8, 5.8 ×10⁸/kg. All patients underwent an alternative donor SCT. The each age at transplant for patients were 8, 18,11 months.

The patients had rapid and durable engraftment at day +13, +16, +23 with minimal complications.No regimen related toxicity were observed, and no viral re-activation (CMV, EBV, VZV) were seen. Each patients developed acute GVHD involving skin only (grade I - II).One of three patients developed chronic GVHD (skin only limited type). All patients are alive and transfusion independent with each follow-up time of 61, 56, 33 months.

Allo-BMT from an unrelated donor is a curative and suitable approach for patients with amegakaryocytic thrombocytopenia with radio-ulnar synostosis (CTRUS), reduced intensity conditioning might be a feasible approach to stem-cell transplantation in patients who do not have a sibling donor. In our three cases, the mutation in exon 2 of HOXA11 gene was not found, which may suggest that these cases are possibly a subtype of this syndrome.Careful clinical course watching is required if another complications or the disease relapse will occur again.

No relevant conflicts of interest to declare.