Stem Cell Transplantation in Fanconi Anemia – Recent Advances with Alternative Donors

Abstract

Bone marrow transplantation from an HLA-identical sibling donor is the treatment of choice for Fanconi anemia (FA) patients with bone marrow failure. However, with today's small size families less than 25% of FA patients have a matching sibling donor. The remaining patients can be treated with stem cell transplantations from alternative donors such as matched unrelated or haploidentical donors. While results with conventional bone marrow transplantation continually improved, outcome after alternative donor transplantation remained poor due to high rates of transplant-related complications, graft rejection and graft-versus-host disease (GvHD). Recently, advances with less myeloablative and more immunosuppressive conditioning regimens have demonstrated promising results. Insights into the mechanisms of immune reconstitution could show that at least in children immune recovery after haploidentical stem cell transplantation is fast and results in complete restoration of normal immune function within the first year after transplantation. Finally, innovations in the field of stem cell collection and processing have led to cellular graft compositions which now provide reliable engraftment in almost all patients with concomitant low incidence of GvHD. This review discusses these recent advances in alternative donor transplantations and concludes that this treatment option should be an early recommendation for FA patients with bone marrow failure who lack an HLA-identical sibling donor.Although the name of the disease suggests a purely hematological disorder, Fanconi anemia (FA) is a systemic disease which is characterized by physical abnormalities, progressive bone marrow failure and increased risk of malignancies. A typical diagnostic feature, which might in part explain some of these symptoms, is increased chromosome breakage at baseline, and even more

Consensus of German Transplant Centers on Hematopoietic Stem Cell Transplantation in Fanconi Anemia

“…Over the past 3 decades, modifications to FA HSCT conditioning regimens together with advances in transplant medicine (e. g. more accurate HLA typing, better supportive care, graft processing, etc.) have dramatically improved the prognosis of FA HSCT [20]. Reduction of chemotherapy and radiation doses (reduced intensity conditioning) lessened RRTs [27,63].…”