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Adoptive transfer of mature T cells (ATMTC) through bone marrow (BM) transplantation, first attempted over 20 years ago, has recently emerged as a successful therapy for complete 22q deletion syndrome (22qDS). This provides a potential option to thymic transplantation (TT) for immune reconstitution in 22qDS. Compared to thymic transplant, ATMTC is an easier procedure to accomplish and is available at more centers. However, there are differences in the nature of the T-cell reconstitution that results. Predictably, more naïve T cells and recent thymic emigrants are present in patients treated with thymus transplant. There are no significant differences in mortality between the two procedures, but the number of patients is too limited to conclude that the procedures are equally effective. Adoptive transfer should be pursued as a reasonable treatment for 22qDS patients requiring immune reconstitution when thymus transplant is not available. [ABSTRACT FROM AUTHOR]

Background: Therapeutic options for DiGeorge syndrome (DGS) with profound T-cell deficiency are very limited. Thymic transplantation has shown promising results but is not easily available. Hematopoietic cell transplantation (HCT) has been successful in restoring immune competence in the short term. Objective: Present the long-term follow-up of 2 patients with complete DGS who received bone marrow transplants in the neonatal period from HLA-matched siblings, and perform a multicenter survey to document the status of other patients with DGS who have undergone HCT. Methods: Immune function assessment by immunophenotyping, lymphocyte proliferation, T-cell receptor excision circles, single nucleotide polymorphism mapping arrays, spectratyping, cytogenetics, and fluorescence in situ hybridization were used. Results: Among reported patients with DGS receiving HCT, survival is greater than 75%. Our patients are in their 20s and in good health. Their hematopoietic compartment shows continuous engraftment with mixed chimerism, normal T-cell function, and humoral immunity. Circulating T cells exhibit a memory phenotype with a restricted repertoire and are devoid of T-cell receptor excision circles. Conclusion: These features suggest that T-cell reconstitution has occurred predominantly through expansion of the donors'' mature T-cell pool. Although restricted, their immune systems are capable of providing substantial protection to infection and respond to vaccines. We conclude that bone marrow transplant achieves long-lived reconstitution of immune function in complete DGS and is a good alternative to thymic transplantation in patients with a suitable donor. Clinical implications: Bone marrow transplant in complete DGS using an HLA-matched sibling donor provides long-lasting immunity and is a suitable and more available alternative to thymic transplantation. [Copyright &y& Elsevier]

ABSTRACT: In Part I of this series the diagnosis of a pediatric immunodeficiency was discussed. In that article key history and exam findings were discussed to help alert the clinician to a problem. Part II will further the knowledge of immunodeficiencies by describing some of the common immunodeficiencies. Diseases affecting neutrophil granule function, specific B-cell or T-cell function, combined T and B cell function and newer syndromes that have multi-system involvement, their diagnosis, and treatment are presented here. The genetic links for many of these diseases are known, and described in this article. Today most large medical centers are able to perform the appropriate diagnostic testing to assure early diagnosis and rapid treatment with aggressive antibiotic regimens and intravenous immunoglobulin. In many cases early bone marrow transplantation is curative or vital to survival. The diagnosis of an immunodeficiency in a child can be overwhelming to the family as well as the primary care clinician. A well armed clinician, knowledgable in the principles of immunodeficiencies, their diagnosis, and treatment can be an active and vital member of the multi-disciplinary team that will care for these challenging children. [Copyright &y& Elsevier]

Background We noted a recent increase in the number of patients with CMV viremia among immunocompromised children at our institution. The study was undertaken to determine the prevalence of CMV viremia and to evaluate factors associated with the development of antiviral drug resistance. Methods A retrospective study of immunocompromised hosts 0–21 years of age who had CMV viremia (2007–2017). We collected demographic data as well as details of antiviral therapy and resistance testing. Results A total of 31 patients were identified including 10 (32%) during the last 2 years. The age range was 3 months to 20 years (median 12.6 years); 23 (74%) were male and 12 (39%) were African American. Among the 31 patients, 18 had hematopoietic stem cell transplantation, 5 had primary immunodeficiency (2 common variable immunodeficiency, 1 SCID, 1 Langerhans cell histiocytosis, 1 DiGeorge syndrome), 4 had malignancies receiving chemotherapy, 3 with heart transplantation and one 17 year old with newly diagnosed HIV infection who presented with CMV pneumonia and viremia. Antiviral resistance testing was performed on 7 CMV isolates: 5 due to persistent viremia (> 1 months) despite treatment, and 2 prior to starting antiviral therapy. CMV resistance was identified in 3 patients including 2 with CVID and one with Hodgkin's disease status post bone marrow transplantation. The 2 CVID patients had other comorbidities including chronic diarrhea and malabsorption and were TPN dependent. Both were diagnosed with CMV colitis and one also had pneumonitis. One had received a prolonged oral valganciclovir course (> 1 year) prior to diagnosis of resistance and the other received long-term intermittent oral valganciclovir courses. The patient with Hodgkin's disease received a prolonged IV ganciclovir course. All 3 tested positive for UL97 mutation and one had both UL97/UL54 gene mutations. Conclusion Most of our patients with CMV viremia were transplant patients. Antiviral drug resistance was detected among 3 of 31 (10%) of our patients during the study period. Two had malabsorption that may have resulted in sub-therapeutic blood levels. Treatment with oral valganciclovir should be avoided in patients with poor gut absorption because it may increase risk of drug resistance. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]