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Successful HLA haploidentical hematopoietic SCT in chronic granulomatous disease

Bone Marrow Transplantation volume 49, pages 1337–1338 (2014)Cite this article

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Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect of phagocytic cells that renders them incapable of producing reactive oxygen metabolites required for microbial killing, most commonly due to mutations of the cytochrome b-245 beta polypeptide (CYBB; MIM# 300481).1 Recurrent life-threatening bacterial and fungal infections and granulomata formation are the hallmarks of this disorder. The prognosis is dismal unless continued antimicrobial prophylaxis is instituted early on, which may limit infectious complications.2,3 A potentially curative approach is allogeneic hematopoietic SCT (HSCT), as shown by several groups.4,5 This therapy, however, has so far only been applied successfully in patients with available HLA-compatible donors, including 9/10 and 10/10 HLA-matched related and unrelated donor transplants as well as 4/6 and 5/6 unrelated cord transplants.6 In a single case report of an HLA-haploidentical HSCT following reduced intensity conditioning, the patient had a secondary graft failure and required a second successful transplant using an unrelated cord blood graft (5/6 match).7 Here we report the first successful HLA-haploidentical SCT in CGD, which indicates the possibility of a broader application of SCT in patients lacking alternative therapeutic options.

In contrast to the patient mentioned above7 who experienced graft failure following reduced-intensity conditioning, engraftment in our patient was sustained and included both lymphoid and myeloid lineages. This experience indicates the importance of myeloablative conditioning in order to avoid graft rejection and to ensure long-term myeloid engraftment in CGD following T-cell-depleted, HLA-haploidentical HSCT. The considerable delay in the T-cell reconstitution, which is typically observed in patients undergoing T-cell-depleted, HLA-haploidentical HSCT, poses a considerable threat of developing viral infections. The fact that patients with CGD are not at increased risk for chronic viral infections prior to transplantation, in contrast to patients with primary T-cell immunodeficiencies, might be an important aspect for the risk–benefit ratio of HLA-haploidentical transplantation for CGD. The most important factor to cure a patient with CGD from refractory fungal disease is the establishment of normal neutrophil functions. This was achieved without delay by the approach described here. Our experience demonstrates that HLA-haploidentical transplantation can be a curative therapeutic option in CGD patients with uncontrolled infections lacking therapeutic alternatives.

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Authors and Affiliations

  1. Department of Pediatrics, University Medical Center Ulm, Ulm, Germany

    M Hoenig, E-M Jacobsen, C Schütz, I Furlan, G Lahr, K-M Debatin, W Friedrich & A Schulz

  2. Department of Pediatrics, Academic Hospital of RWTH Medical School Aachen, Germany, HELIOS Klinikum, Krefeld, Germany

    T Niehues, K Siepermann & G Dückers

  3. Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden Württemberg-Hessen and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany

    M Wiesneth

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  1. M Hoenig
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Correspondence to M Hoenig.

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Hoenig, M., Niehues, T., Siepermann, K. et al. Successful HLA haploidentical hematopoietic SCT in chronic granulomatous disease. Bone Marrow Transplant 49, 1337–1338 (2014). https://doi.org/10.1038/bmt.2014.125

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