Bone marrow transplant using fludarabine‐based reduced intensity conditioning regimen with in vivo T cell depletion in patients with Fanconi anemia

• Published in: Pediatric transplantation Vol. 25; no. 4; pp. e14009 - n/a
• Main Authors: Gorfinkel, Lev, Demsky, Carolyn, Pashankar, Farzana, Kupfer, Gary, Shah, Niketa C.
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.06.2021
• Subjects: allogeneic stem cell transplant; Bone Marrow Transplantation; Busulfan; Child; Chimerism; Cyclophosphamide; Cyclosporins; Drug Therapy, Combination; Fanconi anemia; Fanconi Anemia - immunology; Fanconi Anemia - therapy; Fanconi syndrome; Fludarabine; Genomic instability; Graft-versus-host reaction; Humans; Immune reconstitution; in‐vivo T cell depletion; Lymphocyte Depletion - methods; Lymphocytes T; Monoclonal antibodies; Mycophenolic acid; Myeloablative Agonists - therapeutic use; Prophylaxis; reduced intensity conditioning; Siblings; Stem cell transplantation; T-Lymphocytes - immunology; Transplantation Conditioning - methods; Transplants & implants; Vidarabine - analogs & derivatives; Vidarabine - therapeutic use; in-vivo T cell depletion; Fanconi anemia; reduced intensity conditioning; allogeneic stem cell transplant
• ISSN: 1397-3142; 1399-3046
• DOI: 10.1111/petr.14009

FA is the most common cause of inherited BMF syndromes. The only cure for BMF in FA remains HSCT. Due to DNA instability in FA, RIC has been used to decrease immediate and late complications of HSCT. Most FA conditioning regimens in mismatched and unrelated donor transplants rely on TBI, which increases the risk of secondary malignancies. Most of the non‐TBI conditioning regimens use an ex vivo T‐cell depletion approach, but this is not feasible at all pediatric stem cell transplant programs. To evaluate the success of HSCT in patients with FA using non‐TBI conditioning regimens with in vivo T‐cell depletion approach. HSCT using non‐TBI based conditioning was performed on two siblings with FA. The first sibling underwent matched unrelated donor transplant with a BM graft using fludarabine, alemtuzumab, busulfan, and cyclophosphamide conditioning and cyclosporine and mycophenolate as GVHD prophylaxis. The second sibling underwent MSD transplant with UCB and BM grafts using similar approach, but without busulfan and mycophenolate. Both siblings had engraftment without signs of acute or chronic GVHD. Acute post‐transplant complications included brief viral reactivations. At last follow‐up, both siblings continued to have full immune reconstitution with stable chimerism. Conditioning regimens without radiation and inclusion of alemtuzumab can lead to successful engraftment without development of GVHD and reduce risk of developing secondary neoplasms, even with unrelated donor transplants.