Allogeneic HSCT in Adolescents and Young Adults With Primary Immunodeficiencies

Morris, Emma; Albert, Michael H.

doi:10.3389/fped.2019.00437

Cited by 15 publications

(10 citation statements)

References 36 publications

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“…Allo-HSCT is an adoptive immunotherapy method to treat hematologic malignancies, bone marrow hematopoietic diseases and genetic metabolic disorders [7]. Allo-HSCT has become one of the rare methods to cure leukemia in clinical for those with high risk blood system disease [1,3].…”

Section: Discussionmentioning

confidence: 99%

The Value of Predictive Nursing in Perioperative Period of Allogeneic Hematopoietic Stem Cell Transplantation

Pan¹,

Chen²

2020

SJCM

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Section: Discussionmentioning

confidence: 99%

The Value of Predictive Nursing in Perioperative Period of Allogeneic Hematopoietic Stem Cell Transplantation

Pan¹,

Chen²

2020

SJCM

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“…More than 400 PIDs have been described and they are broadly classified into the following groups: combined immunodeficiencies, immune regulatory disorders, phagocytic defects, autoinflammatory disorders, defects in intrinsic or innate immunity, antibody deficiencies and complement deficiencies (Table I). 3 While most patients present in childhood and adolescence, increasingly patients are being diagnosed later in life as an initial mild phenotype may not prompt investigation for PID 4 …”

Section: Pid Classification Disease Phenotype Genetic Defect/inheritance Treatmentmentioning

confidence: 99%

“…Historically older patients with PID had abysmal transplant outcomes but more recently, much improved survival rates for alloHSCT have been achieved in older patients with PID using reduced‐intensity conditioning (RIC) regimens 12,13 . There has been a paradigm shift in practice in recent years and patients who develop severe complications of PID later in life are increasingly considered for definitive treatment should their clinical scenario permit it 4 …”

Section: Pid Classification Disease Phenotype Genetic Defect/inheritance Treatmentmentioning

confidence: 99%

Gene therapy for primary immunodeficiencies

Fox

Booth

2020

Br J Haematol

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Summary Primary immunodeficiencies (PIDs) are a group of rare inherited disorders of the immune system. Many PIDs are devastating and require a definitive therapy to prevent progressive morbidity and premature mortality. Allogeneic haematopoietic stem cell transplantation (alloHSCT) is curative for many PIDs, and while advances have resulted in improved outcomes, the procedure still carries a risk of mortality and morbidity from graft failure or graft‐versus‐host disease (GvHD). Autologous haematopoietic stem cell gene therapy (HSC GT) has the potential to correct genetic defects across haematopoietic lineages without the complications of an allogeneic approach. HSC GT for PID has been in development for the last two decades and the first licensed HSC‐GT product for adenosine deaminase‐deficient severe combined immunodeficiency (ADA‐SCID) is now available. New gene editing technologies have the potential to circumvent some of the problems associated with viral gene‐addition. HSC GT for PID shows great promise, but requires a unique approach for each disease and carries risks, notably insertional mutagenesis from gamma‐retroviral gene addition approaches and possible off‐target toxicities from gene‐editing techniques. In this review, we discuss the development of HSC GT for PID and outline the current state of clinical development before discussing future developments in the field.

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“…16 There is a growing body of publications detailing outcome data on approximately 200 cases of allo-HSCT for PID in adults. 4,5,11,[17][18][19][20][21][22][23][24][25] Additional data on a similar number of adults have been published in abstract form. In most published series, the overall survival was equivalent to that achieved in children and infants being in excess of 80% at a median follow-up of between 14 months and 5 years.…”

Section: Background On Natural History Of Pid In Adults and Data In Amentioning

confidence: 99%

Allogeneic hematopoietic stem cell transplantation in adults with primary immunodeficiency

Morris

2020

Hematology

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With recent advances in genetic sequencing and its widespread adoption for clinical diagnostics, the identification of a primary immunodeficiency (PID) as the underlying cause of diseases presenting to hematologists including refractory autoimmunity, cytopenias, immune dysregulation, and hematologic malignancy, is increasing, particularly in the adult population. Where the pathogenic genetic variants are restricted to the hematopoietic system, selected patients may benefit from allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although it is generally accepted that early allo-HSCT (ie, in infancy or childhood) for PID is preferable, this is not always possible. The clinical phenotype of non–severe combined immune deficiency forms of PID can be very heterogeneous, in part because of the high number of genetic and functional defects affecting T, B, and natural killer cells, neutrophils, and/or antigen presentation. As a result, some patients have less severe disease manifestations in childhood and/or a later de novo presentation. For others, a delayed diagnosis, lack of a genetic diagnosis, or a previous lack of a suitable donor has precluded prior allo-HSCT. Specific issues which make transplantation for adult PID patients particularly challenging are discussed, including understanding the natural history of rare diseases and predicting outcome with conservative management alone; indications for and optimal timing of transplant; donor selection; conditioning regimens; and PID-specific transplant management. The role of gene therapy approaches as an alternative to allo-HSCT in high-risk monogenic PID is also discussed.

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Allogeneic HSCT in Adolescents and Young Adults With Primary Immunodeficiencies

Cited by 15 publications

References 36 publications

The Value of Predictive Nursing in Perioperative Period of Allogeneic Hematopoietic Stem Cell Transplantation

The Value of Predictive Nursing in Perioperative Period of Allogeneic Hematopoietic Stem Cell Transplantation

Gene therapy for primary immunodeficiencies

Allogeneic hematopoietic stem cell transplantation in adults with primary immunodeficiency

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