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

Publication Type:

Journal Article

Source:

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

Keywords:

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

Abstract:

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.