Long-Term Clinical Outcomes of Severe Combined Immunodeficiency Patients Given Nonablative Marrow Transplants

Hardin, Olga; Lokhnygina, Yuliya; Buckley, Rebecca H.

doi:10.1016/j.jaip.2021.11.032

Cited by 16 publications

(10 citation statements)

References 28 publications

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“…SCID diagnosis was targeted for newborn screening (NBS) given the high morbidity and mortality rate in early infancy due to infections, the negative impact of preexisting infections and resulting organ damage on survival posttransplant, and the improved survival and outcome of early hematopoietic stem cell transplant (HSCT) in infants identified due to family history [20 ▪ ,30,31 ▪ ]. T-cell receptor (TCR) excision circles (TRECs) are stable circular DNA molecules produced as a byproduct of TCR rearrangement; TRECs can be quantitated from a blood spot using PCR to indicate the presence of T cells [18].…”

Section: Immunodeficiency In Classical Il-2 Receptor Gamma Null Defec...mentioning

confidence: 99%

“…Consortiums have been formed to collect clinical data on these rare transplants, with the goal of identifying factors and designing protocols that may lead to improved outcomes. At US centers, HSCT at less than 3.5 months of age was associated with the highest overall survival rates [30,31 ▪ ], while the European registry did not find that age at HSCT is associated with overall survival [20 ▪ ]. Multiple studies have identified infection prior to transplant, and particularly active infection at HSCT, as being associated with survival rates up to 40% lower than uninfected children [19,20 ▪ ,30,35].…”

Section: Immunodeficiency In Classical Il-2 Receptor Gamma Null Defec...mentioning

confidence: 99%

“…Matched related transplants were associated with the best survival in most studies, while Human Leukocyte Antigen (HLA)-mismatched transplants were associated with worse outcomes [30,35]. Mismatched and even haplo-identical transplants can be performed with lower rates of graft-versus-host disease (GVHD) graft rejection, and survival if the graft is TCRαβ and/or CD19 depleted [31 ▪ ,36 ▪ ,37].…”

Section: Immunodeficiency In Classical Il-2 Receptor Gamma Null Defec...mentioning

confidence: 99%

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A great disturbance in the force: IL-2 receptor defects disrupt immune homeostasis

Hernandez

Hsieh

2022

Current Opinion in Pediatrics

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Purpose of reviewThe current review highlights how inborn errors of immunity (IEI) due to IL-2 receptor (IL-2R) subunit defects may result in children presenting with a wide variety of infectious and inflammatory presentations beyond typical X-linked severe combined immune deficiency (X-SCID) associated with IL-2Rγ.Recent findingsNewborn screening has made diagnosis of typical SCID presenting with severe infections less common. Instead, infants are typically diagnosed in the first days of life when they appear healthy. Although earlier diagnosis has improved clinical outcomes for X-SCID, atypical SCID or other IEI not detected on newborn screening may present with more limited infectious presentations and/or profound immune dysregulation. Early management to prevent/control infections and reduce inflammatory complications is important for optimal outcomes of definitive therapies. Hematopoietic stem cell transplant (HSCT) is curative for IL-2Rα, IL-2Rβ, and IL-2Rγ defects, but gene therapy may yield comparable results for X-SCID.SummaryDefects in IL-2R subunits present with infectious and inflammatory phenotypes that should raise clinician's concern for IEI. Immunophenotyping may support the suspicion for diagnosis, but ultimately genetic studies will confirm the diagnosis and enable family counseling. Management of infectious and inflammatory complications will determine the success of gene therapy or HSCT.

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Section: Immunodeficiency In Classical Il-2 Receptor Gamma Null Defec...mentioning

confidence: 99%

Section: Immunodeficiency In Classical Il-2 Receptor Gamma Null Defec...mentioning

confidence: 99%

Section: Immunodeficiency In Classical Il-2 Receptor Gamma Null Defec...mentioning

confidence: 99%

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A great disturbance in the force: IL-2 receptor defects disrupt immune homeostasis

Hernandez

Hsieh

2022

Current Opinion in Pediatrics

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“…Hematopoietic stem cell transplantation (HSCT), enzyme replacement therapy for adenosine deaminase (ADA) deficiency, and gene therapy in some disease types are the only curative treatments today that allow not only to save life but also to ensure its quality ( 3 ). Studies of this disorders for the past 20 years show a considerably high chance of survival in those who underwent HSCT before 3.5 months of age, reaching up to 94% survival rate over 6 years ( 3 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

Newborn screening for severe combined immunodeficiency: The results of the first pilot TREC and KREC study in Ukraine with involving of 10,350 neonates

Boyarchuk

Yarema

Kravets³

et al. 2022

Front. Immunol.

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Severe combined immunodeficiency (SCID) is a group of inborn errors of immunity (IEI) characterized by severe T-and/or B-lymphopenia. At birth, there are usually no clinical signs of the disease, but in the first year of life, often in the first months the disease manifests with severe infections. Timely diagnosis and treatment play a crucial role in patient survival. In Ukraine, the expansion of hemostatic stem cell transplantation and the development of a registry of bone marrow donors in the last few years have created opportunities for early correction of IEI and improving the quality and life expectancy of children with SCID. For the first time in Ukraine, we initiated a pilot study on newborn screening for severe combined immunodeficiency and T-cell lymphopenia by determining T cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs). The analysis of TREC and KREC was performed by real-time polymerase chain reaction (RT-PCR) followed by analysis of melting curves in neonatal dry blood spots (DBS). The DBS samples were collected between May 2020 and January 2022. In total, 10,350 newborns were screened. Sixty-five blood DNA samples were used for control: 25 from patients with ataxia-telangiectasia, 37 -from patients with Nijmegen breakage syndrome, 1with X-linked agammaglobulinemia, 2with SCID (JAK3 deficiency and DCLRE1C deficiency). Retest from the first DBS was provided in 5.8% of patients. New sample test was needed in 73 (0.7%) of newborns. Referral to confirm or rule out the diagnosis was used in 3 cases, including one urgent abnormal value. CID (T low B+NK+) was confirmed in a patient with the urgent abnormal value. The results of a pilot study in Ukraine are compared to other studies (the referral rate 1: 3,450). Approbation of the Frontiers in Immunology frontiersin.org 01

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“…[29][30]. Unfortunately, some patients with PIDD do not recover B cell function following HCT, these patients may also be candidates for longer term posttransplant SCIG [31].…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Hizentra ® Following Pediatric Hematopoietic Cell Transplant for Treatment of Primary Immunodeficiencies

Patel

Torgerson²,

Thakar³

et al. 2022

Preprint

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Primary Immunodeficiency disease (PIDD) comprise a group of disorders of immune function. Some of the most severe PIDD can be treated with hematopoietic cell transplant (HCT). Hizentra® is a 20% liquid IgG product approved for subcutaneous administration in adults and children greater than two years of age with PIDD-associated antibody deficiency. Limited information is available on use of Hizentra® in children following HCT for PIDD. A multicenter retrospective chart review demonstrated 37 infants and children (median age 70.1 [range 12.0 to 176.4] months) with PIDD treated by HCT who received Hizentra® infusions over a median duration of 31 (range 4-96) months post-transplant. The most common indication for HCT was IL2RG SCID (n=16). Thirty-two patients switched from IVIG to SCIG administration, due to one or more of the following reasons: patient/caregiver (n=17) or physician (n=12) preference, discontinuation of central venous catheter (n=16), desire for home infusion (n=12), improved IgG serum levels following lower levels on IVIG (n=10), and loss of venous access (n=8). Serious bacterial infections occurred at a rate of 0.041 per patient-year while on therapy. Weight percentile increased by a mean of 16% during the observation period, with females demonstrating the largest gains. Mild local reactions were observed in 24%; 76% had no local reactions. One serious adverse event (death from sepsis) was reported. Hizentra® was discontinued in 15 (41%) patients, most commonly due to recovery of B-cell function (n=11). These data demonstrate that Hizentra® is a safe and effective option in children who have received HCT for PIDD.

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Long-Term Clinical Outcomes of Severe Combined Immunodeficiency Patients Given Nonablative Marrow Transplants

Cited by 16 publications

References 28 publications

A great disturbance in the force: IL-2 receptor defects disrupt immune homeostasis

A great disturbance in the force: IL-2 receptor defects disrupt immune homeostasis

Newborn screening for severe combined immunodeficiency: The results of the first pilot TREC and KREC study in Ukraine with involving of 10,350 neonates

Safety and Efficacy of Hizentra ® Following Pediatric Hematopoietic Cell Transplant for Treatment of Primary Immunodeficiencies

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