Evidence map›Paper›PMID 39233015›Full record

Trial reportThe Journal of allergy and clinical immunology2025

Hematopoietic cell transplantation for DOCK8 deficiency: Results from a prospective clinical trial.

Alexandra F Freeman, Corina E Gonzalez, Bonnie Yates, Kristen Cole, Lauren Little, Erin Flannelly, Seth M Steinberg, George Mo, Nicole Piette, Thomas E Hughes and 13 more

Registry-linked trialAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of allergy and clinical immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01176006 (Related and Unrelated Donor Hematopoietic Stem Cell Transplant for DOCK8 Deficiency), which is not on this map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01176006 phase2active not recruitingnot on this map

Related and Unrelated Donor Hematopoietic Stem Cell Transplant for DOCK8 Deficiency

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2010 to 2028Enrolled70ConditionsDOCK8 DeficiencyArmsReduced-intensity hematopoietic stem cell, Fludarabine(Fludara, Berlex Laboratories), Cyclophosphamide(CTX, Cytoxan), Total Body Irradiation (TBI), Busulfan (Busulfex)
3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Emerging Paediatric Uses of Dupilumab Beyond Approvals.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2026
    Review
  2. Article
  3. Fungal Infections in Disorders of Inborn Errors of Immunity.Clinical reviews in allergy & immunology · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Alexandra F FreemanLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
Corina E GonzalezImmune-Deficiency Cellular Therapy Program, National Cancer Institute, Bethesda, Md. Electronic address: corina.gonzalez@nih.gov.
Bonnie YatesPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Md.
Kristen ColeTransplant and Cell Therapy Program, Clinical Center, Bethesda, Md.
Lauren LittlePediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Md.
Erin FlannellyImmune-Deficiency Cellular Therapy Program, National Cancer Institute, Bethesda, Md.
Seth M SteinbergBiostatistics and Data Management Section, National Cancer Institute, Bethesda, Md.
George MoPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Md.
Nicole PiettePharmacy Department, Bethesda, Md.
Thomas E HughesPharmacy Department, Bethesda, Md.
Jennifer Cuellar-RodriguezLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
Juan Gea-BanaclocheLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
Theo HellerNational Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md.
Dima A HammoudCenter for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, Bethesda, Md.
Steve M HollandLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
Heidi H KongDermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Md.
Fernanda D YoungLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
Huie JingLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
Basak KayaogluLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
Helen C SuLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
Sung-Yun PaiImmune-Deficiency Cellular Therapy Program, National Cancer Institute, Bethesda, Md.
Dennis D HicksteinImmune-Deficiency Cellular Therapy Program, National Cancer Institute, Bethesda, Md.
Nirali N ShahPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Md.

Funding

ID-CTP Clinical CoreZIDBC012026 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PAI, SUNG-YUN · 2021 to 2025
$10.7M
Immunotherapeutic approaches to treat pediatric hematologic malignanciesZIABC011823 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SHAH, NIRALI · 2019 to 2025
$6.1M
Understanding DOCK8 Function in Health and Human DiseaseZIAAI001193 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, HELEN CHUN-HUI · 2014 to 2025
$4.5M
Intramural NIH HHS Z99 CA999999Intramural NIH HHS ZIA AI001193Intramural NIH HHS ZIA BC011823Intramural NIH HHS ZID BC012026
6 · The paper itself

Abstract

backgroundDOCK8 deficiency is a primary immunodeficiency in which allogeneic hematopoietic cell transplantation (HCT) represents the only known cure. We tested the ability of a busulfan-based regimen to achieve reliable engraftment and high levels of donor chimerism with acceptable toxicity in a prospective clinical trial in DOCK8 deficiency.

objectivesTo both evaluate the ability of HCT to reverse the clinical phenotype and to correct the immunologic abnormalities by 1 year post HCT.

methodsWe conducted a prospective HCT trial for recipients with DOCK8 deficiency. Subjects were recruited from October 5, 2010, to December 30, 2022. Donor sources included fully matched related and unrelated donors and haploidentical donors. The reduced toxicity, myeloablative conditioning regimen contained no serotherapy. Graft-versus-host disease (GVHD) prophylaxis included either a calcineurin inhibitor with methotrexate or post-HCT cyclophosphamide (PT/Cy) followed by tacrolimus and mycophenolate mofetil. The trial was later amended to study PT/Cy in all patients. (Pilot Study of Reduced-Intensity Hematopoietic Stem Cell Transplant of DOCK8 [NCT01176006].)

resultsThirty-six subjects, both children and adults (median age 16.4 years), underwent HCT for DOCK8 deficiency. Most patients, 33 of 36 (92%), achieved full (≥98%) donor chimerism in whole blood as early as day +30. With a median potential follow-up of 7.4 years, 29 (80.6%) were alive with no evidence of new DOCK8 deficiency-related complications. PT/Cy was effective in reducing the risk of acute GVHD in patients who had received matched unrelated donor and haploidentical transplants, but it was associated with transient delays in immune-reconstitution and hemorrhagic cystitis.

conclusionsA busulfan-based HCT regimen using PT/Cy for GVHD prophylaxis and a broad range of donor types and hematopoietic cell sources were well tolerated, leading to the reversal of the clinical immunophenotype.

Indexed as

Graft vs Host DiseaseGuanine Nucleotide Exchange FactorsHematopoietic Stem Cell TransplantationTransplantation ConditioningAdolescentAdultBusulfanChildChild, PreschoolFemaleHumansMalePrimary Immunodeficiency DiseasesProspective StudiesYoung AdultBusulfanDOCK8 protein, humanGuanine Nucleotide Exchange FactorsDOCK8 deficiencyhematopoietic cell transplantationimmunophenotype reversal

Identifiers

PMID39233015
PMCPMC11700784

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.