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Successful treatment of autoimmune lymphoproliferative syndrome and refractory autoimmune thrombocytopenic purpura with a reduced intensity conditioning stem cell transplantation followed by donor lymphocyte infusion

Bone Marrow Transplantation volume 40, pages 605–606 (2007)Cite this article

Autoimmune lymphoproliferative syndrome (ALPS) is caused by mutations of the genes encoding for Fas receptor (CD95), Fas ligand or other genes involved in apoptosis.1, 2, 3 When Fas binds to Fas ligand, intracellular signal transduction and caspase activation lead to apoptosis, which is important for lymphocyte homoeostasis and immune tolerance by elimination of autoreactive cells. Failure of lymphocyte apoptosis leads to accumulation of autoreactive clones and lymphoproliferation. ALPS is a clinically and genetically heterogeneous disease.

The syndrome includes type 0, caused by homozygous Fas mutations with complete Fas deficiency and severe clinical features, type Ia with heterozygous Fas mutations, type Ib with heterozygous FAS-ligand mutations, type II with caspase-10 mutations and type III with no identifiable mutation. Fas mutations have variable penetrance, according to the mutated gene domain.1 Clinical course is variable and includes lymphoproliferation with lymphadenopathy, splenomegaly or hepatomegaly and various autoimmune phenomena.3, 4 Hypergammaglobulinaemia, autoantibodies and increased CD4 and CD8 double-negative T cells are typical.1, 3 There is an increased risk for lymphoproliferative malignancies.5

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Authors and Affiliations

  1. Department of Haematology, Royal Free Hospital, London, UK

    M N Dimopoulou, S Gandhi, R Chakraverty, A Fielding, S Mackinnon & P D Kottaridis

  2. Cambridge Blood Centre, Cambridge, UK

    C Ghevaert

  3. Department of Immunology, Royal Free Hospital, London, UK

    D Webster

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  1. M N Dimopoulou
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  2. S Gandhi
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  3. C Ghevaert
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  7. S Mackinnon
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  8. P D Kottaridis
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Correspondence to P D Kottaridis.

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Dimopoulou, M., Gandhi, S., Ghevaert, C. et al. Successful treatment of autoimmune lymphoproliferative syndrome and refractory autoimmune thrombocytopenic purpura with a reduced intensity conditioning stem cell transplantation followed by donor lymphocyte infusion. Bone Marrow Transplant 40, 605–606 (2007). https://doi.org/10.1038/sj.bmt.1705775

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