{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:07:04Z","timestamp":1770041224225,"version":"3.49.0"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008322","name":"CSL Behring","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Background<\/jats:title><jats:p>Patients with chronic lymphocytic leukemia (CLL) experience hypogammaglobinemia and non-neutropenic infections. In this exploratory proof of concept study, our objective was to determine the prevalence of humoral immunodeficiency in patients with CLL and serum IgG \u2265 400 mg\/dL, and to evaluate the efficacy of subcutaneous immunoglobulin (SCIG) in this population.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Patients and methods<\/jats:title><jats:p>Patients with CLL with serum IgG \u2265 400 mg\/dL were evaluated for serum IgG, IgM, IgA, along with pre\/post vaccine IgG titers to diphtheria, tetanus, and<jats:italic>Streptococcus pneumoniae<\/jats:italic>. Patients with evidence of humoral dysfunction were treated with SCIG with Hizentra every 7\u00b12 days for 24 weeks.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>Fifteen patients enrolled with median IgG = 782 mg\/dL [IQR: 570 to 827], and 6\/15 (40%) responded to vaccination with Td, while 5\/15 (33%) responded to vaccination with PPV23. 14\/15 (93.3%) demonstrated humoral immunodeficiency as evidenced by suboptimal vaccine responses, and were treated with SCIG. In patients treated with SCIG, serum IgG increased from 670 mg\/dL [IQR: 565 to 819] to 1054 mg\/dL [IQR: 1040 to 1166] after 24 weeks (95% CI: 271\u2013540). For<jats:italic>streptococcus pneumoniae<\/jats:italic>, the median protective serotypes at baseline was 8 [IQR: 4 to 9] and increased to 17 [IQR: 17 to 19] after 24 weeks (95% CI: 6.93\u201313.72). Non-neutropenic infections (NNI) decreased from 14 to 5 during treatment with SCIG.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusions<\/jats:title><jats:p>Patients with CLL demonstrate humoral immunodeficiency despite IgG &gt; 400 mg\/dL. For these patients, SCIG is well tolerated and efficacious in improving serum IgG, specific IgG to<jats:italic>streptococcus pneumoniae<\/jats:italic>, and may decrease reliance on antibiotics for the treatment of NNIs.<\/jats:p><\/jats:sec><jats:sec id=\"sec005\"><jats:title>Clinical trials registration<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03730129\" xlink:type=\"simple\">NCT 03730129<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0258529","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T18:18:47Z","timestamp":1634321927000},"page":"e0258529","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Subcutaneous immunoglobulin replacement for treatment of humoral immune dysfunction in patients with chronic lymphocytic leukemia"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9691-7590","authenticated-orcid":true,"given":"S. Shahzad","family":"Mustafa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saad","family":"Jamshed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karthik","family":"Vadamalai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison","family":"Ramsey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"issue":"1","key":"pone.0258529.ref001","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer Statistics 2019","volume":"69","author":"RL Siegel","year":"2019","journal-title":"Cancer Journal for Clinicians"},{"key":"pone.0258529.ref002","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1001\/archinte.1973.03650100076014","article-title":"Infections complicating multiple myeloma and chronic lymphocytic leukemia","volume":"132","author":"JJ Twomey","year":"1973","journal-title":"Arch Int Med"},{"key":"pone.0258529.ref003","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s00282-999-0145-0","article-title":"Infectious complications in chronic lymphocytic leukemia","volume":"41","author":"E Morra","year":"1999","journal-title":"Hematological Cell Therapies"},{"issue":"3","key":"pone.0258529.ref004","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s10875-014-9995-5","article-title":"Antibody deficiency secondary to chronic lymphocytic leukemia: Should patients be treated with prophylactic replacement immunoglobulin?","volume":"34","author":"F Dhalla","year":"2014","journal-title":"Journal of Clinical Immunology"},{"issue":"9","key":"pone.0258529.ref005","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1182\/blood.V96.9.3168","article-title":"Chronic lymphocytic leukemia B cells inhibit spontaneous Ig production by autologous bone marrow cells: role of CD95-CD95L interaction","volume":"96","author":"A Sampalo","year":"2000","journal-title":"Blood"},{"issue":"5","key":"pone.0258529.ref006","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/bjh.12067","article-title":"Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia","volume":"159","author":"D Oscier","year":"2012","journal-title":"British Journal of Haematology"},{"key":"pone.0258529.ref007","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1056\/NEJM198810063191403","article-title":"Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia, Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia. 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Humoral immunodeficiency in patients with chronic lymphocytic leukemia. Abstract. 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