Cyclophosphamide-based in vivo T-cell depletion for HLA-haploidentical transplantation in Fanconi anemia.

Publication Type:

Journal Article


Pediatric hematology and oncology, Volume 29, Issue 6, p.568-78 (2012)


2012, Adolescent, Antineoplastic Agents, Center-Authored Paper, Child, Clinical Research Division, Combined Modality Therapy, Fanconi Anemia, Female, Follow-Up Studies, Graft Rejection, Graft vs Host Disease, hematopoietic stem cell transplantation, HLA Antigens, Humans, Immune Monitoring Core Facility, Lymphocyte Depletion, Research Trials Office Core Facility - Biostatistics Service, Shared Resources, T-Lymphocytes, Transplantation Chimera, Transplantation Conditioning, Transplantation, Homologous, Vidarabine


Allogeneic hematopoietic cell transplantation (HCT) is the only known cure for patients with Fanconi anemia (FA) who develop aplasia or leukemia. However, transplant regimens typically contain high-dose alkylators, which are poorly tolerated in FA patients. Furthermore, as many patients lack human leukocyte antigen (HLA)-matched family donors, alternative donors are used, which can increase the risk of both graft rejection and graft-versus-host disease (GVHD). To improve on these three concerns, we developed a multi-institutional clinical trial using a fludarabine (FLU)-based conditioning regimen with limited alkylators/low-dose radiation, HLA-haploidentical marrow, followed by reduced-dose cyclophosphamide (CY) to treat three FA patients with aplasia. All three patients engrafted with 100% donor CD3 chimerism at 1 month. One patient died early from disseminated toxoplasmosis infection. Of the two survivors, one had significant pretransplant co-morbidities and inadequate immunosuppression, and developed severe acute GVHD. The other patient had only mild acute and no chronic GVHD. With a follow-up of 2 and 3 years, respectively, both patients are doing well, are transfusion-independent, and maintain full donor chimerism. The patient with severe GVHD has resolving oral GVHD and good quality of life. We conclude that using low-intensity conditioning, HLA-haploidentical marrow, and reduced-dose CY for in vivo T-cell depletion can correct life-threatening aplasia in FA patients.