PMID- 22839094
OWN - NLM
STAT- MEDLINE
DCOM- 20130228
LR  - 20211021
IS  - 1521-0669 (Electronic)
IS  - 0888-0018 (Print)
IS  - 0888-0018 (Linking)
VI  - 29
IP  - 6
DP  - 2012 Sep
TI  - Cyclophosphamide-based in vivo T-cell depletion for HLA-haploidentical 
      transplantation in Fanconi anemia.
PG  - 568-78
LID - 10.3109/08880018.2012.708708 [doi]
AB  - 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.
FAU - Thakar, M S
AU  - Thakar MS
AD  - Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. mthakar@mcw.edu
FAU - Bonfim, C
AU  - Bonfim C
FAU - Sandmaier, B M
AU  - Sandmaier BM
FAU - O'Donnell, P
AU  - O'Donnell P
FAU - Ribeiro, L
AU  - Ribeiro L
FAU - Gooley, T
AU  - Gooley T
FAU - Deeg, H J
AU  - Deeg HJ
FAU - Flowers, M E
AU  - Flowers ME
FAU - Pasquini, R
AU  - Pasquini R
FAU - Storb, R
AU  - Storb R
FAU - Woolfrey, A E
AU  - Woolfrey AE
FAU - Kiem, H P
AU  - Kiem HP
LA  - eng
GR  - P01 HL036444/HL/NHLBI NIH HHS/United States
GR  - P30 CA015704/CA/NCI NIH HHS/United States
GR  - HL036444/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120727
PL  - England
TA  - Pediatr Hematol Oncol
JT  - Pediatric hematology and oncology
JID - 8700164
RN  - 0 (Antineoplastic Agents)
RN  - 0 (HLA Antigens)
RN  - FA2DM6879K (Vidarabine)
RN  - P2K93U8740 (fludarabine)
SB  - IM
MH  - Adolescent
MH  - Antineoplastic Agents/therapeutic use
MH  - Child
MH  - Combined Modality Therapy
MH  - Fanconi Anemia/immunology/*therapy
MH  - Female
MH  - Follow-Up Studies
MH  - Graft Rejection/*prevention & control
MH  - Graft vs Host Disease/*prevention & control
MH  - HLA Antigens/*immunology
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - *Lymphocyte Depletion
MH  - T-Lymphocytes/*immunology
MH  - Transplantation Chimera/immunology
MH  - Transplantation Conditioning
MH  - Transplantation, Homologous
MH  - Vidarabine/*analogs & derivatives/therapeutic use
PMC - PMC3622043
MID - NIHMS454654
EDAT- 2012/07/31 06:00
MHDA- 2013/03/01 06:00
PMCR- 2013/09/01
CRDT- 2012/07/31 06:00
PHST- 2012/07/31 06:00 [entrez]
PHST- 2012/07/31 06:00 [pubmed]
PHST- 2013/03/01 06:00 [medline]
PHST- 2013/09/01 00:00 [pmc-release]
AID - 10.3109/08880018.2012.708708 [doi]
PST - ppublish
SO  - Pediatr Hematol Oncol. 2012 Sep;29(6):568-78. doi: 10.3109/08880018.2012.708708. 
      Epub 2012 Jul 27.