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Klin Padiatr 2008; 220(3): 147-152
DOI: 10.1055/s-2008-1065326
Original Article

© Georg Thieme Verlag KG Stuttgart · New York

Favourable Long-Term Outcome after Matched Sibling Transplantation for Fanconi-Anemia (FA) and in vivo T-Cell Depletion

Langzeitergebnisse nach HLA-identischer Geschwistertransplantation bei Fanconi-Anämie und In-vivo-T-Zell-DepletionK. Huck 1 [*] , H. Hanenberg 1 , 2 [*] , W. Nürnberger 1 , 3 , D. Dilloo 1 , S. Burdach 1 , 4 , U. Göbel 1 , H. J. Laws 1
  • 1Klinik für Kinder-Onkologie, -Hämatologie und Klinische Immunologie, Zentrum für Kinder- und Jugendmedizin, Heinrich-Heine-Universität, Düsseldorf, Germany
  • 2Department of Pediatrics, Wells Center for Pediatric Research, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA
  • 3Current address: Klinik für Knochenmarktransplantation und Hämatologie/Onkologie GmbH, Sektion Pädiatrie, Idar-Oberstein
  • 4Current address: Klinik und Poliklinik für Kinder- und Jugendmedizin, Kinderklinik München Schwabing, Technische Universität München, Germany
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Publication History

Publication Date:
13 May 2008 (online)

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Abstract

Hematopoietic stem cell transplantation is the only permanent treatment for the hematological manifestations in Fanconi anemia (FA). As FA patients have a dramatically increased intrinsic propensity to develop malignancies later in life and the genotoxic stress afflicted during conditioning advances the manifestation age especially of squamous cell carcinomas, choosing an optimally suited treatment regimen appears critical for long-term, tumor-free survival after stem cell transplantation. Here, we report our experiences in 6 consecutive FA patients transplanted with HLA-matched sibling donors where we combined an established pre-transplantation treatment consisting of thoraco-abdominal irradiation (TAI), cyclophosphamide (CYC) and cyclosporine A graft-versus-host prophylaxis with antibody-mediated in vivo T-cell depletion strategies after infusion of the graft. This approach has ensured sustained engraftment with long-term survival and an excellent post transplant performance status without any evidence of secondary malignancies in all six patients after a median follow-up of more than 10 years.

Zusammenfassung

Die hämatogene Stammzelltransplantation ist die einzige definitve Therapieoption für das progrediente Knochenmarkversagen bei Fanconi-Anämie (FA). Da FA-Patienten ein sehr hohes intrinsisches Risiko für die Entwicklung von Malignomen tragen und die zusätzliche Behandlung mit genotoxischen Substanzen die Manifestation vor allem von Plattenepithelkarzinomen beschleunigen kann, ist die Art des Konditionierungsregimes entscheidend für das tumorfreie Langzeitüberleben nach Stammzelltransplantation. Wir stellen hier unsere Erfahrung mit sechs aufeinanderfolgenden HLA-identischen Familienspender-Transplantationen bei FA dar, bei denen wir ein etabliertes Konditionierungsprotokoll mit thorako-abdominaler Bestrahlung, Cyclophosphamid und Cyclosporin A zur GvHD-Prophylaxe mit der intravenösen Gabe von Antikörpern zur in-vivo -T-Zell-Depletion nach Infusion des Transplantates kombiniert haben. Dieses Vorgehen führte bei allen sechs Patienten zu einer anhaltend stabilen Hämatopoese und ereignisfreiem Langzeitüberleben ohne Hinweise auf Sekundärmalignome nach einer medianen Nachbeobachtungszeit von mehr als 10 Jahren.

Key words

Fanconi anemia - stem cell transplantation - secondary malignancies - GvHD - CD25 monoclonal antibody

Schlüsselwörter

Fanconi-Anämie - Stammzelltransplantation - GvHD - monoklonaler CD25-Antiköper - Sekundärmalignome

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H. HanenbergMD 

Children's Hospital

Heinrich Heine University

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Phone: +49/211/811 76 80

Fax: +49/211/811 94 36

Email: Hanenberg@uni-duesseldorf.de

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