Over the past 20 years, hematopoietic stem cell transplantation (HSCT) outcomes in patients with Fanconi Anaemia (FA) have improved dramatically. It is well established that the addition of mesenchymal stem cells (MSCs) to HSCT regimens in aplastic anaemias has positive effects on transplantation results. Considering these results, we present the transplantation procedure successfully performed on a patient with FA, supported by the MSC infusion from a 9/10 HLA-matched unrelated donor.

An 11-year-old girl was admitted with multiple congenital anomalies and pancytopenia. DEB test was positive, compound heterozygous FANCA mutation was detected. A diagnosis of Fanconi anemia (FA) was made. We continued administering oral prednisolone and danazol without transfusion for 3 years. The need for platelet transfusion guided us to schedule HSCT. Given the absence of any matched family donor in her case, a 9/10 HLA matched donor was found from the national stem cell bank. Reduced-intensity conditioning regimen (Fludarabine, 30 mg/m2/day, days -7 to -3; cyclophosphamide; CY, 10 mg/kg/day, days -6 to -3) and serotherapy (ATG, 10 mg/kg/day, days -4 to -2) were performed. Mesenchymal stem cells (MSC) infusion (1 × 106/kg) was administered on days -1 and +7, along with a dose of 6.2 × 106/kg peripheral stem cells. Tacrolimus, methotrexate, and prednisolone (1 mg/kg/day, 28 days) were administered as graft versus host disease (GVHD) prophylaxis. Neutrophil engraftment (2020/mm3) occurred on the 9th day, platelet engraftment (135000/mm3) occurred on the 12th day. She had CMV reactivation in the 3rd month of HSCT. Antiviral treatment for CMV infection was carried out for 3 weeks. On day +100, a steroid was added due to grade II skin acute GVHD (aGVHD). Following its tapering off after 15 days, steroid administration was stopped. The patient achieved complete chimerism, allowing the discontinuation of immunosuppressive treatments in the first year itself.

MRD and MUD transplants yield the highest success rate in patients with FA. However, the results of HSCT from an alternative donor are still unsatisfactory. MSCs are responsible for immune regulation, tissue repair and regeneration, homing, and support of the hematopoietic system. It has been reported that infusion of MSCs can reduce the development of aGVHD by 3-fold and improve the OS of patients after allogeneic HSCT in comparison to standard prophylaxis. The addition of MSC to the conditioning regimens for MMUD transplants in patients with FA has been proven advantageous due to its graft-supporting, immunosuppressive, and immunomodulatory properties. However, large-scale randomised controlled trials are yet required to back these benefits.

Keywords:Fanconi anemia, HSCT, mesenchymal stem cell