Faculty Collaboration Database

Cyclophosphamide-based in vivo T-cell depletion for HLA-haploidentical transplantation in Fanconi anemia. Pediatr Hematol Oncol 2012 Sep;29(6):568-78

Date

07/31/2012

Pubmed ID

22839094

Pubmed Central ID

PMC3622043

DOI

10.3109/08880018.2012.708708

Scopus ID

2-s2.0-84865314809 (requires institutional sign-in at Scopus site)   25 Citations

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.

Author List

Thakar MS, Bonfim C, Sandmaier BM, O'Donnell P, Ribeiro L, Gooley T, Deeg HJ, Flowers ME, Pasquini R, Storb R, Woolfrey AE, Kiem HP

MESH terms used to index this publication - Major topics in bold

Adolescent
Antineoplastic Agents
Child
Combined Modality Therapy
Fanconi Anemia
Female
Follow-Up Studies
Graft Rejection
Graft vs Host Disease
HLA Antigens
Hematopoietic Stem Cell Transplantation
Humans
Lymphocyte Depletion
T-Lymphocytes
Transplantation Chimera
Transplantation Conditioning
Transplantation, Homologous
Vidarabine