{"doi":"10.1172/jci164918","title":"A phase III randomized crossover trial of plerixafor versus G-CSF for treatment of WHIM syndrome","abstract":"BACKGROUNDWarts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a primary immunodeficiency disorder caused by heterozygous gain-of-function CXCR4 mutations. Myelokathexis is a kind of neutropenia caused by neutrophil retention in bone marrow and in WHIM syndrome is associated with lymphopenia and monocytopenia. The CXCR4 antagonist plerixafor mobilizes leukocytes to the blood; however, its safety and efficacy in WHIM syndrome are undefined.METHODSIn this investigator-initiated, single-center, quadruple-masked phase III crossover trial, we compared the total infection severity score (TISS) as the primary endpoint in an intent-to-treat manner in 19 patients with WHIM who each received 12 months treatment with plerixafor and 12 months treatment with granulocyte CSF (G-CSF, the standard of care for severe congenital neutropenia). The treatment order was randomized for each patient.RESULTSPlerixafor was nonsuperior to G-CSF for TISS (P = 0.54). In exploratory endpoints, plerixafor was noninferior to G-CSF for maintaining neutrophil counts of more than 500 cells/μL (P = 0.023) and was superior to G-CSF for maintaining lymphocyte counts above 1,000 cells/μL (P < 0.0001). Complete regression of a subset of large wart areas occurred on plerixafor in 5 of 7 patients with major wart burdens at baseline. Transient rash occurred on plerixafor, and bone pain was more common on G-CSF. There were no significant differences in drug preference or quality of life or the incidence of drug failure or serious adverse events.CONCLUSIONPlerixafor was not superior to G-CSF in patients with WHIM for TISS, the primary endpoint. Together with wart regression and hematologic improvement, the infection severity results support continued study of plerixafor as a potential treatment for WHIM syndrome.TRIAL REGISTRATIONClinicaltrials.gov NCT02231879.FUNDINGThis study was funded by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases.","journal":"Journal of Clinical Investigation","year":2023,"id":321978,"datarank":1.1905611036562722,"base_score":3.7612001156935624,"endowment":3.7612001156935624,"self_citation_contribution":0.5641800173540344,"citation_network_contribution":0.6263810863022378,"self_endowment_contribution":0.5641800173540344,"citer_contribution":0.6263810863022378,"corpus_percentile":null,"corpus_rank":null,"citation_count":42,"citer_count":35,"citers_with_citation_signal":25,"citers_with_endowment":25,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9576,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02231879"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":418896,"name":"Daniel Velez","orcid":null,"position":1,"is_corresponding":false},{"id":418897,"name":"Elena Cho","orcid":null,"position":2,"is_corresponding":false},{"id":286643,"name":"Edward W. 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Jeffrey Kim","orcid":null,"position":12,"is_corresponding":false},{"id":106036,"name":"Carmen C. Brewer","orcid":"0000-0003-1462-049X","position":13,"is_corresponding":false},{"id":284428,"name":"James D. Katz","orcid":"0000-0002-2098-8883","position":14,"is_corresponding":false},{"id":231246,"name":"Douglas B. Kuhns","orcid":"0000-0002-9971-0760","position":15,"is_corresponding":false},{"id":238416,"name":"Harry L. Malech","orcid":"0000-0001-5874-5775","position":16,"is_corresponding":false},{"id":98407,"name":"Dean Follmann","orcid":null,"position":17,"is_corresponding":false},{"id":399107,"name":"Michael P. Fay","orcid":"0000-0002-8643-9625","position":18,"is_corresponding":false},{"id":86111,"name":"Philip M. Murphy","orcid":"0000-0002-1080-8201","position":19,"is_corresponding":false},{"id":78735,"name":"David H. McDermott","orcid":"0000-0001-6978-0867","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T01:07:37.596550Z","pmid":"37561579","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}