Evidence map›Paper›PMID 31385931›Full record

ArticleTransplantation2020

Impact of CMV Reactivation, Treatment Approaches, and Immune Reconstitution in a Nonmyeloablative Tolerance Induction Protocol in Cynomolgus Macaques.

Paula Alonso-Guallart, Raimon Duran-Struuck, Jonah S Zitsman, Stephen Sameroff, Marcus Pereira, Jeffrey Stern, Erik Berglund, Nathaly Llore, Genevieve Pierre, Emily Lopes and 13 more

Open access · greenAbstract read
In one paragraph

Article in Transplantation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 37% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Helical TomoTherapy Total Lymphoid Irradiation and Hematopoietic Cell Transplantation for Kidney Transplant Tolerance in Rhesus Macaques.Transplant international : official journal of the European Society for Organ Transplantation · 2023
    Article
  3. Immunophenotyping of Rhesus CMV-Specific CD8 T-Cell Populations.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2021
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 3 institutions in 2 countries.

Paula Alonso-GuallartColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
Raimon Duran-StruuckColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
Jonah S ZitsmanColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
Stephen SameroffCenter for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York, NY.
Marcus PereiraDivision of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, NY.
Jeffrey SternColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
Erik BerglundColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
Nathaly LloreColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
Genevieve PierreColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
Emily LopesColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
Sigal B KofmanColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
Makenzie DantonColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
Hugo P SondermeijerColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
David WoodlandColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
Yojiro KatoColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
Dilrukshi K Ekanayake-AlperColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
Alina C IugaDepartment of Pathology and Cell Biology, Columbia University, New York, NY.
Cheng-Shie WuuDepartment of Radiation Oncology, Columbia University Medical Center, New York, NY.
Anette WuColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
W Ian LipkinCenter for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York, NY.
Rafal TokarzCenter for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York, NY.
Megan SykesColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
Adam GriesemerColumbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.
Columbia University Irving Medical Center · USColumbia University · USUniversity of Pennsylvania · US

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
Translational Biomarker Analytical Core (TBAC)P30DK063608 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Anthony W Ferrante · 2003 to 2026
$36.7M
Using Polyclonal Tregs to Develop a Compressed BMT Regiment for Deceased Donor Islets and KidneysU19AI131474 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SYKES, MEGAN · 2017 to 2022
$12.1M
MECHANISMS OF BETA CELL FAILURER01DK064819 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ACCILI, DOMENICO · 2003 to 2025
$10.5M
Robust allograft tolerance in non-human primatesR01OD017949 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SYKES, MEGAN · 2015 to 2019
$4.5M
BD Biosciences InfluxS10OD020056 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SNOECK, HANS-WILLEM E · 2015 to 2015
$600k
NCI NIH HHS P30 CA013696NIAID NIH HHS U19 AI131474NIDDK NIH HHS P30 DK063608NIDDK NIH HHS R01 DK064819NIH HHS R01 OD017949
6 · The paper itself

Abstract

backgroundCytomegalovirus (CMV) infection is a serious complication in immunosuppressed patients, specifically transplant recipients. Here, we describe the development and use of an assay to monitor the incidence and treatment of CMV viremia in a Cynomolgus macaque model of bone marrow transplantation (BMT) for tolerance induction. We address the correlation between the course of viremia and immune reconstitution.

methodsTwenty-one animals received a nonmyeloablative conditioning regimen. Seven received cyclosporine A for 28 days and 14 received rapamycin. A CMV polymerase chain reaction assay was developed and run twice per week to monitor viremia. Nineteen recipients were CMV seropositive before BMT. Immune reconstitution was monitored through flow cytometry and CMV viremia was tracked via quantitative polymerase chain reaction.

resultsRecipients developed CMV viremia during the first month post-BMT. Two animals developed uncontrollable CMV disease. CMV reactivation occurred earlier in cyclosporine A-treated animals compared with those receiving rapamycin. Post-BMT, T-cell counts remained significantly lower compared with pretransplant levels until CMV reactivation, at which point they increased during the viremic phase and approached pretransplant levels 3 months post-BMT. Management of CMV required treatment before viremia reached 10 000 copies/mL; otherwise clinical symptoms were observed. High doses of ganciclovir resolved the viremia, which could subsequently be controlled with valganciclovir.

conclusionsWe developed an assay to monitor CMV in Cynomolgus macaques. CMV reactivation occurred in 100% of seropositive animals in this model. Rapamycin delayed CMV reactivation and ganciclovir treatment was effective at high doses. As in humans, CD8 T cells proliferated during CMV viremia.

Indexed as

Immune ToleranceVirus ActivationAnimalsAntifungal AgentsBone Marrow TransplantationCytomegalovirusCytomegalovirus InfectionsDisease Models, AnimalGraft RejectionImmune ReconstitutionMacaca fascicularisSirolimusTransplant RecipientsAntifungal AgentsSirolimus

Identifiers

PMID31385931
PMCPMC6994365
OpenAlexW2965181056

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.