Evidence map›Paper›PMID 35083501›Full record

Observational studyCancer chemotherapy and pharmacology2022

Effects of cyclophosphamide related genetic variants on clinical outcomes of adult hematopoietic cell transplant patients.

Takuto Takahashi, Rachael Pearson, Qing Cao, Aileen Scheibner, Kinjal Sanghavi, Daniel Weisdorf, Claudio Brunstein, John Rogosheske, Veronika Bachanova, Erica D Warlick and 2 more

Abstract readObservational Study
PubMed Publisher
In one paragraph

Observational study in Cancer chemotherapy and pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
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

12 authors at 3 institutions in 1 country.

Takuto TakahashiDivision of Pediatric Hematology/Oncology/Blood and Marrow Transplant, University of Minnesota, Minneapolis, MN, USA. takah033@umn.edu.ORCID 0000-0001-8296-6412
Rachael PearsonDepartment of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota College of Pharmacy, Minneapolis, MN, USA.
Qing CaoBiostatistics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Aileen ScheibnerDepartment of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota College of Pharmacy, Minneapolis, MN, USA.
Kinjal SanghaviDepartment of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota College of Pharmacy, Minneapolis, MN, USA.
Daniel WeisdorfDivision of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Claudio BrunsteinDivision of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
John RogosheskeDepartment of Pharmacy, Fairview MHealth, Minneapolis, MN, USA.
Veronika BachanovaDivision of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Erica D WarlickDivision of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Anthony WisemanUniversity of Minnesota Medical School, Minneapolis, MN, USA.
Pamala A JacobsonDepartment of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota College of Pharmacy, Minneapolis, MN, USA.
University of Minnesota · USEssentia Health · USFairview Health Services · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Timothy C. Hallstrom · 1998 to 2026
$100.4M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR002494 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, WEISDORF, DANIEL J · 2018 to 2022
$34.9M
NIH HHS P30CA077598NIH HHS UL1-TR002494
6 · The paper itself

Abstract

purposeGenetic variants may influence the pharmacokinetics and pharmacodynamics (PKPD) of cyclophosphamide (CY). CY plays a critical role in conditioning chemotherapy for hematopoietic cell transplantation (HCT), but its use is limited by toxicity. We explored the effect of genetic variants, potentially affecting PKPD of CY, and outcomes after HCT.

methodsThis observational pharmacogenomic study included 85 adults with hematologic malignancies who received reduced intensity conditioning with CY, fludarabine, and total body irradiation. We collected recipient DNA prior to HCT and evaluated 97 candidate variants in 66 genes and 3 metabolism phenotypes potentially involved in PKPD pathways of CY. In multivariable analysis we investigated the association between the genotypes and four clinical outcomes: Day 180 non-relapse mortality (NRM) and day 180 overall survival (OS), acute graft-versus-host-disease (aGVHD) grades 2-4, and engraftment. p values were not adjusted for multiple testing.

resultsThe median recipient age was 63 years (range 21-75). Acute myeloid leukemia was the most common diagnosis (34%; n = 29). In multivariable analysis adjusted for exposure to phosphoramide mustard, the final active metabolite of CY, we identified 6 variants in 6 genes associated with at least one of the clinical outcomes. An ABCC4 variant (rs9561778) was associated with poor Day 180 NRM (p < 0.01), MUTYH variant (rs3219484) with higher Day 180 NRM and aGVHD (both p < 0.01), and SYNE1 variant (rs4331993) with better Day 180 OS and engraftment (both p ≤ 0.01).

conclusionThe present study suggests that genetic variants influencing the PKPD of CY may help identify patients at risk for inferior outcomes after HCT using CY-based reduced-intensity conditioning.

Indexed as

Graft vs Host DiseaseHematopoietic Stem Cell TransplantationCyclophosphamideHumansTransplantation ConditioningWhole-Body IrradiationCyclophosphamideBone marrow transplantCyclophosphamideHematopoietic cell transplantationPharmacogeneticsPharmacogenomics

Identifiers

PMID35083501
OpenAlexW4210768021

What OpenQuestion holds

Textmetadata
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.