Patients with adenosine deaminase deficiency surviving after hem

Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications
Manfred Hönig1, Michael H. Albert2, Ansgar Schulz1, Monika Sparber-Sauer1,
Catharina Schütz1, Bernd Belohradsky2, Tayfun Güngör3, Markus T. Rojewski4, Harald Bode1, Ulrich Pannicke4, Dominique Lippold4, Klaus Schwarz4, Klaus-Michael Debatin1, Michael S. Hershfield5, and Wilhelm Friedrich1

1 Department of Pediatrics, University of Ulm, Germany; 2 Dr von Haunersches Kinderspital, Ludwig Maximilians University Munich, Germany; 3 Division of Immunology/Hematology/BMT, University Children’s Hospital, Zürich, Switzerland; 4 Institute for Transfusion Medicine, University Hospital of Ulm and Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; 5 Duke Medical Center, Duke University, Durham, NC

Adenosine deaminase (ADA) deficiency is a systemic metabolic disease that causes an autosomal recessive variant of severe combined immunodeficiency (SCID) and less consistently other complications including neurologic abnormalities. Hematopoietic stem cell transplantation (HSCT) is able to correct the immunodeficiency, whereas control of nonimmunologic complications has not been extensively explored. We applied HSCT in 15 ADA-deficient patients consecutively treated at our institutions since 1982 and analyzed long-term outcome. Seven patients received transplants without conditioning from HLA-matched family donors (MFDs); the other 8 patients received conditioning and were given transplants either from HLA-mismatched family donors (MMFDs; n = 6) or from matched unrelated donors (MUDs; n = 2). At a mean follow-up period of 12 years (range, 4-22 years), 12 patients are alive with stable and complete immune reconstitution (7 of 7 after MFD, 4 of 6 after MMFD, and 1 of 2 after MUD transplantation). Six of 12 surviving patients show marked neurologic abnormalities, which include mental retardation, motor dysfunction, and sensorineural hearing deficit. We were unable to identify disease or transplantation-related factors correlating with this divergent neurologic outcome. The high rate of neurologic abnormalities observed in long-term surviving patients with ADA deficiency indicates that HSCT commonly fails to control CNS complications in this metabolic disease.

Blood, 15 April 2007, Vol. 109, No. 8, pp. 3595-3602.
Prepublished online as a Blood First Edition Paper on December 21, 2006; DOI 10.1182/blood-2006-07-034678.

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