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Hematopoietic stem cell transplantation in severe congenital neutropenia

Authors

  • G. Carlsson MD, PhD,

    1. Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
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  • J. Winiarski MD, PhD,

    1. Department of Pediatrics, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
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  • P. Ljungman MD, PhD,

    1. Hematology Center, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
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  • O. Ringdén MD, PhD,

    1. Centre of Allogeneic Stem Cell Transplantation, Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
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  • J. Mattsson MD, PhD,

    1. Centre of Allogeneic Stem Cell Transplantation, Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
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  • M. Nordenskjöld MD, PhD,

    1. Clinical Genetics Unit, Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
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  • I. Touw PhD,

    1. Department of Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
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  • J.-I. Henter MD, PhD,

    1. Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
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  • J. Palmblad MD, PhD,

    1. Hematology Center, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
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  • B. Fadeel MD, PhD,

    1. Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
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  • H. Hägglund MD, PhD

    Corresponding author
    1. Hematology Center, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    • Hematology Center, Department of Medicine, Karolinska University Hospital, Stockholm 141 86, Sweden.
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  • Conflict of interest: Nothing to declare.

Abstract

Background

Severe congenital neutropenia (SCN) is an immunodeficiency characterized by disturbed myelopoiesis and an absolute neutrophil count (ANC) <0.5 × 109/L. SCN is also a premalignant condition; a significant proportion of patients develop myelodysplastic syndrome or leukemia (MDS/L). Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for SCN.

Procedure

Since 2004, eight HSCT have been performed in seven patients at our center. The indications were transformation to MDS/L (n = 2), granulocyte colony-stimulating factor receptor (CSF3R) mutation(s) (n = 2), granulocyte colony-stimulating factor (G-CSF) resistance (n = 2), and at the patient's own request (n = 1).

Results

The mean age at transplantation was 13 years (2.8–28 years) (mean follow-up 32 months, range 21–60). Three patients harbored ELANE mutations, three HAX1 mutations, and in one patient no causative mutation was identified. Two of the ELANE mutations were novel mutations. Three patients initially received myeloablative conditioning and four had reduced intensity conditioning (RIC). Three grafts were from HLA-identical siblings, three from matched unrelated donors and two were cord blood units. Engraftment occurred in all patients. Two of seven (29%) patients died; both had MDS/L and both were among the three that underwent myeloablative conditioning. One patient has chronic GVHD 2 years post-transplant.

Conclusions

The role of HSCT should be explored further in patients with SCN. In particular, the influence of the conditioning regime needs to be evaluated in a larger cohort of patients. Pediatr Blood Cancer 2011;56:444–451. © 2010 Wiley-Liss, Inc.

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