Evidence map›Paper›PMID 37042921›Full record

ArticleBlood advances2023

Alemtuzumab and CXCL9 levels predict likelihood of sustained engraftment after reduced-intensity conditioning HCT.

Ashley V Geerlinks, Brooks Scull, Christa Krupski, Ryan Fleischmann, Michael A Pulsipher, Mary Eapen, James A Connelly, Catherine M Bollard, Sung-Yun Pai, Christine N Duncan and 17 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01998633 (Reduced-Intensity Conditioning for Children and Adults With Hemophagocytic Syndromes or Selected Primary Immune Deficiencies), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
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.

NCT01998633 phase2completednot on this map

Reduced-Intensity Conditioning for Children and Adults With Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (RICHI) (BMT CTN #1204)

TypeinterventionalSponsorMedical College of WisconsinRan2013 to 2016Enrolled47ConditionsHemophagocytic Lymphohistiocytosis, Chronic Active Epstein-Barr Virus Infection, Chronic Granulomatous Disease, HIGM-1ArmsHematopoietic Stem Cell Transplant
3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 5 citations in OpenAlex.

  1. 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

27 authors at 17 institutions in 3 countries.

Ashley V GeerlinksDivision Hematology and Oncology, Children's Hospital at London Health Sciences Centre, Western University, London, ON, Canada.
Brooks ScullDivision of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
Christa KrupskiDivision of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Ryan FleischmannDivision of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
Michael A PulsipherDivision of Hematology and Oncology, Primary Children's Hospital, Huntsman Cancer Institute, Spencer Fox Eccles School of Medicine at the University of Utah, Salt Lake City, UT.ORCID 0000-0003-3030-8420
Mary EapenDivision of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.
James A ConnellyDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, TN.
Catherine M BollardCenter for Cancer and Immunology Research, Children's National Hospital and The George Washington University, Washington, DC.
Sung-Yun PaiNational Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD.
Christine N DuncanDana-Farber Cancer Institute, Boston Children's Hospital, Boston, MA.
Leslie S KeanDana-Farber Cancer Institute, Boston Children's Hospital, Boston, MA.
K Scott BakerClinical Research Division, Fred Hutchinson Cancer Center and Department of Pediatrics, University of Washington School of Medicine, Seattle, WA.
Lauri M BurroughsClinical Research Division, Fred Hutchinson Cancer Center and Department of Pediatrics, University of Washington School of Medicine, Seattle, WA.
Jeffrey R AndolinaDepartment of Pediatrics, Golisano Children's Hospital, University of Rochester Medical Center, Rochester, NY.ORCID 0000-0001-6502-6859
Shalini ShenoyDivision of Pediatric Hematology-Oncology, Washington University School of Medicine, St. Louis, MO.
Philip RoehrsPediatric Hematology/Oncology, Department of Pediatrics, University of Virginia, Charlottesville, VA.
Rabi HannaDepartment of Pediatric Hematology and Oncology and BMT, Cleveland Clinic, Cleveland, OH.
Julie-An TalanoDivision of Pediatric Hematology/Oncology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI.
Kirk R SchultzDivision of Pediatric Hematology and Oncology, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0002-0001-6438
Elizabeth O StengerAflac Center and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University, Atlanta, GA.
Howard LinTexas Children's Cancer and Hematology Center, Texas Children's Hospital, Houston, TX.
Adi Zoref-LorenzHematology Institute, Meir Medical Center, Kfar Saba, Israel.
Kenneth L McClainDivision of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX.ORCID 0000-0003-0725-6263
Michael B JordanDivision of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Tsz-Kwong ManDivision of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
Carl E AllenDivision of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
Rebecca A MarshDivision of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Baylor College of Medicine · USCincinnati Children's Hospital Medical Center · USBoston Children's Hospital · USMedical College of Wisconsin · USUniversity of Washington · USCleveland Clinic · USEmory University · USGeorge Washington University Hospital · USNational Institutes of Health · USPrimary Children's Hospital · USTexas Children's Hospital · USUniversity of British Columbia · CAUniversity of Rochester Medical Center · USUniversity of Virginia · USVanderbilt University Medical Center · USWashington University in St. Louis · USWestern University · CA

Funding

Blood and Marrow Transplant Clinical Trials Network DCC- The Medical College of Wisconsin, Inc.U24HL138660 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI Steven M. DeVine, Mehdi Hussain Hamadani · 2017 to 2026
$71.4M
PB vs. BMU01HL069294 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI HOROWITZ, MARY MARESCA · 2001 to 2010
$63.3M
Easy-to-read Informed Consent for HCT Clinical TrialsU10HL069294 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI HOROWITZ, MARY MARESCA · 2011 to 2016
$43.8M
Pathobiology and treatment of patients with inborn errors of immunityZIABC012040 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PAI, SUNG-YUN · 2021 to 2025
$7.9M
NHLBI NIH HHS U01 HL069294NHLBI NIH HHS U10 HL069294NHLBI NIH HHS U24 HL138660
6 · The paper itself

Abstract

Overall survival after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) using alemtuzumab, fludarabine, and melphalan is associated with high rates of mixed chimerism (MC) and secondary graft failure (GF). We hypothesized that peritransplantation alemtuzumab levels or specific patterns of inflammation would predict these risks. We assessed samples from the Bone Marrow Transplant Clinical Trials Network 1204 (NCT01998633) to study the impact of alemtuzumab levels and cytokine patterns on MC and impending or established secondary GF (defined as donor chimerism <5% after initial engraftment and/or requirement of cellular intervention). Thirty-three patients with hemophagocytic lymphohistiocytosis (n = 25) and other IEIs (n = 8) who underwent HCTs with T-cell-replete grafts were included. Patients with day 0 alemtuzumab levels ≤0.32 μg/mL had a markedly lower incidence of MC, 14.3%, vs 90.9% in patients with levels >0.32 μg/mL (P = .008). Impending or established secondary GF was only observed in patients with day 0 alemtuzumab levels >0.32 μg/mL (P = .08). Unexpectedly, patients with impending or established secondary GF had lower CXCL9 levels. The cumulative incidence of impending or established secondary GF in patients with a day 14+ CXCL9 level ≤2394 pg/mL (day 14+ median) was 73.6% vs 0% in patients with a level >2394 pg/mL (P = .002). CXCL9 levels inversely correlated with alemtuzumab levels. These data suggest a model in which higher levels of alemtuzumab at day 0 deplete donor T cells, inhibit the graft-versus-marrow reaction (thereby suppressing CXCL9 levels), and adversely affect sustained engraftment in the nonmyeloablative HCT setting. This trial was registered at www.clinicaltrials.gov as #NCT01998633.

Indexed as

Antibodies, Monoclonal, HumanizedHematopoietic Stem Cell TransplantationAlemtuzumabChemokine CXCL9HumansMelphalanTissue DonorsAlemtuzumabAntibodies, Monoclonal, HumanizedChemokine CXCL9CXCL9 protein, humanMelphalan

Identifiers

PMID37042921
PMCPMC10368780
OpenAlexW4365135776

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.