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Stem Cell Transplantation for Primary Immunodeficiency

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Management of Infections in the Immunocompromised Host

Abstract

Primary immunodeficiency diseases (PID) are a group of heterogeneous inherited disorders affecting the development and function of the innate and acquired immune system. The disorders are characterized by increased susceptibility to recurrent and severe infections, autoimmunity and in some cases malignancies. Allogeneic haematopoietic stem cell transplant (HSCT), and in some cases gene therapy, is the only curative approach for many of these disorders. With the expanding field of molecular genetics, new immune disorders are being identified, but the role of HSCT or other therapy in these disorders remains to be determined. This chapter will review the current indications for HSCT in PID and will examine the specific challenges associated with HSCT in (1) severe combined immunodeficiency (SCID) where the landscape is changing due the introduction of newborn screening; (2) other combined immune deficiencies, some of which have only very recently been described; and (3) phagocytic and haemophagocytic cell disorders. The role of alternative therapies including gene therapy and thymic transplantation will also be discussed.

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Abbreviations

ADA:

Adenosine deaminase

APDS:

Activated PI3Kδ syndrome

ATG:

Anti-thymocyte globulin

CGD:

Chronic granulomatous disease

CTLs:

Cytotoxic T lymphocytes

DLI:

Donor lymphocyte infusion

DOCK8:

Dedicator of cytokinesis 8

EBV:

Epstein-Barr virus

FHLH:

Familial haemophagocytic lymphohistiocytosis

GvHD:

Graft versus host disease

HLA:

Human leukocyte antigen

HLH:

Haemophagocytic lymphohistiocytosis

HSCT:

Haematopoietic stem cell transplant

iC9-T:

Inducible human caspase 9

LAD:

Leukocyte adhesion deficiency type 1

MAC:

Myeloablative conditioning

MHC class II:

Major histocompatibility complex class II

MIC:

Minimal intensity conditioning

MMFD:

Mismatched family donor

MRD:

Matched related donor

MSD:

Matched sibling donor

mTOR:

Mammalian target of rapamycin

MUD:

Matched unrelated donor

NBS:

Newborn screening

NKT:

NK+ T cells

OS:

Overall survival

PBSC:

Peripheral blood stem cells

PEG-ADA:

Polyethylene glycol-conjugated adenosine deaminase

PI3K:

Phosphatidylinositol-3 kinase

PID:

Primary immunodeficiency diseases

RIC:

Reduced intensity conditioning

SCETIDE:

Stem cell transplant for immunodeficiencies in Europe

SCID:

Severe combined immunodeficiency

TCR:

T-cell receptor

TRECs:

T-cell receptor excision circles

TRM:

Transplant-related mortality

UCBT:

Umbilical cord blood stem cell transplantation

WAS:

Wiskott-Aldrich syndrome

XIAP:

X-linked inhibitor of apoptosis

XLP:

X-linked lymphoproliferative disease

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Authors and Affiliations

  1. Department of Bone Marrow Transplantation, Great Ormond Street Hospital, London, UK

    Juliana Silva & Paul Veys

  2. Department of Paediatric Immunology, Great Ormond Street Hospital, London, UK

    Claire Booth

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  1. Juliana Silva
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  2. Claire Booth
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  1. Departments of Medicine and Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA

    Brahm H. Segal

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Silva, J., Booth, C., Veys, P. (2018). Stem Cell Transplantation for Primary Immunodeficiency. In: Segal, B. (eds) Management of Infections in the Immunocompromised Host. Springer, Cham. https://doi.org/10.1007/978-3-319-77674-3_19

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  • DOI: https://doi.org/10.1007/978-3-319-77674-3_19

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  • Online ISBN: 978-3-319-77674-3

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