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Adenosine deaminase deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
The discovery of the association between adenosine deaminase (ADA) (EC 3.5.4.4) deficiency and severe combined immunodeficiency disease in the early 1970s [1] provided exciting evidence of metabolic causation of immunodeficiency. This established a relationship between the metabolism of purines and developmental immunobiology, and this was reinforced by the discovery of purine nucleoside phosphorylase deficiency.
Host Defense II: Acquired Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
Defects in either non-specific or specific cellular immunity are associated with increased susceptibility to fungal infection. Examples include myeloperoxidase deficiency (Chapter 10), and purine nucleoside phosphorylase deficiency (Chapter 2).
Immune dysfunction in inborn errors of immunity causing malignancies
Published in Expert Review of Clinical Immunology, 2021
Several national cohorts provided higher incidence for malignancy in IEIs with approximately 1.4 to 5-fold increase compared to age-adjusted general population [6,15,16]. Among the IEI diagnoses in these reports are predominantly antibody deficiencies, especially common variable immunodeficiency (CVID), reported to have a prevalence of malignancy ranging from 88% to 21% combined immunodeficiencies (CIDs), which mainly include Ataxia-telangiectasia (AT), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS); congenital phagocytic disorders, EBV susceptibility disorders and diseases with immune dysregulation [4,7,12]. The United States Immune Deficiency Network Registry reported 1.91-fold excess relative risk of malignancy in men compared with the age-adjusted gender population, while women showed equal rate as normal population. However, the incidence of lymphoma increased 10 times in men and 8.34 times in women [6]. On the other hand, solid organ malignancies of lung, colon, breast and prostate were not found to have a higher frequency in IEI [6,12]. In a study with 6392 Turkish patients with IEI, prevalence of malignancy was reported as 0.9% and found to be 1.57 times more common compared with general population; mostly including CID group as DOCK8 deficiency, AT, Wiskott-Aldrich syndrome (WAS), BS, and purine nucleoside phosphorylase deficiency [15].
T-cell acute lymphoblastic leukemia: promising experimental drugs in clinical development
Published in Expert Opinion on Investigational Drugs, 2023
Arabinosyl guanine (ara-G) is a guanosine nucleoside analog that displays T-cell specificity. It has been developed following observations in patients with purine nucleoside phosphorylase deficiency [23]. Nelarabine, a water-soluble prodrug rapidly converted to ara-G, was then developed [24]. A first phase 1 dose-escalation trial was performed in patients with R/R hematologic malignancies [25]. The dose-limiting toxicity was neurologic. The most common severe neurologic adverse events started within 12 days of drug infusion, and most were reversible. They included somnolence, confusion, ataxia and peripheral neuropathies. The recommended phase 2 dose was 1200 mg/m2/d, which was equivalent to approximately 30 mg/Kg/d in adults and 40 mg/Kg/d in children.
Clinical Profile and Outcomes of Primary Immunodeficiency and Malignancy in Childhood at a Tertiary Oncology Center in Developing Country
Published in Pediatric Hematology and Oncology, 2022
Derya Özyörük, Zeliha Güzelküçük, Ayse Metin, Suna Emir, Arzu Yazal Erdem, Dilek Kacar, Ayca Koca Yozgat, Can Baris Aker, Selma Çakmakçı, Sonay Incesoy Özdemir, Neriman Sari, Meriç Kaymak Cihan, Namık Yasar Özbek, İnci Ergürhan İlhan
The median age of patients with malignancy associated with PID was 8 years (ranges 2–18 years) at the time of the first malignancy. Out of the 23 patients, 14 were male (60%) and 9 were female. Of 23 patients with malignancy associated with PID, 10 (43%) patients had diagnosed with ataxia telangiectasia, 6 (26%) with antibody deficiencies (4 common variable immunodeficiency (CVID), 1 purine nucleoside phosphorylase deficiency (PNP), 1 Ig A deficiency), 2 with CD 27 deficiency, 2 with RAS guanyl-releasing protein 1 (RASGRP1) mutations, 1 with Bloom Syndrome, 1 with Wiskott-Aldrich syndrome and 1 with myeloperoxidase deficiency. A total of 26 malignancies (first or second) in 23 patients were determined in the present study. Non-Hodgkin lymphoma (n = 17; 65%) was the most common malignancy, followed by Hodgkin lymphoma (n = 5; one of them was a second cancer), anaplastic ependymoma (n = 1; as a second cancer), spinal glioblastoma multiforme (n = 1; as a second cancer), 1 retinoblastoma (n = 1) and intracranial hemangiopericytoma (n = 1) in this group. All patients had a history of parental consanguinity. The most common presenting symptom was enlarged lymph nodes and mediastinal mass (n = 16) followed by abdominal mass, jaw swelling, dacryoadenitis, nasal polyps, autoimmune lymphoproliferative syndrome (ALPS) like phenotype (n = 5) in patients with malignant lymphoma and PID. A total 4 (66%) of 6 patients with Lymphoblastic lymphoma, T cell presented with superior vena cava syndrome. Three of 23(13%) patients developed two cancers. Of 21 patients with malignant lymphoma and PID, 19(90%) patients had Stage III/IV, others had Stage II (n = 2;10%) disease. The median time from first symptom to diagnosis was 1 month (ranges 10 days–2 years). The demographic, clinical characteristics and treatment results of patients with malignancy and PID are summarized in Table 1.