ArticleFrontiers in immunology2022
Association between gene polymorphisms in the cyclophosphamide metabolism pathway with complications after haploidentical hematopoietic stem cell transplantation.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Influence of Genetic Variation of GST, CYP, and ABC on the Safety and Efficacy of Cyclophosphamide-Based Therapy.Clinical and translational science · 2025Pooled it
- Critique on "Restrictive versus standard hyperhydration during high-dose cyclophosphamide for hematopoietic stem cell transplantation: a retrospective cohort study".Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Article
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- Fatal interstitial lung disease associated with rituximab in diffuse large B-cell lymphoma: A case report and literature review.Medicine · 2025Review
- Exploring skin aging-associated genotypes; Moving toward delivery of precision medicine-based care more than beyond skin deep care: a genome-wide association study.BMC geriatrics · 2025Article
- Observational
- Gene polymorphisms associated with immunosuppressant adverse effects in systemic lupus erythematosus: a narrative review.Frontiers in genetics · 2025Review
- Impact of cyclosporine A-related single nucleotide polymorphisms on post-transplant outcomes in pediatric hematologic malignancy patients undergoing allogeneic hematopoietic stem cell transplantation.Frontiers in immunology · 2025Article
- Adjuvant Anti-tumor Therapy with Polyphenolic Compounds: A Review.Current medicinal chemistry · 2025Review
- 4-Pyridone-3-carboxamide-1-β-D-ribonucleoside Reduces Cyclophosphamide Effects and Induces Endothelial Inflammation in Murine Breast Cancer Model.International journal of molecular sciences · 2024Article
- Severe toxicities in amazonian populations and the role of precision medicine in acute lymphoblastic leukemia treatment.Scientific reports · 2024Article
- Correlation of Genetic Polymorphism of CYP3A5 to Cyclophosphamide Efficacy and Toxicity in Rhabdomyosarcoma Pediatric Egyptian Cancer Patients.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- ATG or post-transplant cyclophosphamide to prevent GVHD in matched unrelated stem cell transplantation?Leukemia · 2024Article
- The Capacity of Drug-Metabolising Enzymes in Modulating the Therapeutic Efficacy of Drugs to Treat Rhabdomyosarcoma.Cancers · 2024Review
- Association between CYP2B6 genetic variability and cyclophosphamide therapy in pediatric patients with neuroblastoma.Scientific reports · 2023Article
- Review
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for patients with hematologic malignances. Haploidentical HSCT (Haplo-HSCT) is an alternative option for patients who do not have an HLA-matched donor. The use of post-transplantation high dose cyclophosphamide (PT-Cy) is commonly employed for graft-versus-host disease (GVHD) prophylaxis in haplo-HSCT. Cyclophosphamide (Cy) is an alkylating agent with antineoplastic and immunosuppressive activity, whose bioactivation requires the activity of polymorphic enzymes in the liver to produce phosphoramide mustard, which is a DNA alkylating agent. To identify polymorphisms in the genes of Cy metabolism and correlate them with post-HSCT complications [GVHD, sinusoidal obstruction syndrome (SOS), hemorrhagic cystitis (HC) and transplant-related mortality (TRM)], we designed a custom next-generation sequencing panel with Cy metabolism enzymes. We analyzed 182 patients treated with haplo-HSCT with PT-Cy from 2007 to 2019, detecting 40 variants in 11 Cy metabolism genes. Polymorphisms in CYP2B6, a major enzyme involved in Cy activation, were associated with decreased activity of this enzyme and a higher risk of Graf-versus-host disease (GVHD). Variants in other activation enzymes (CYP2A6, CYP2C8, CYP2C9, CYP2C19) lead to decreased enzyme activity and were associated with GVHD. Polymorphisms in detoxification genes such as glutathione S-transferases decreased the ability to detoxify cyclophosphamide metabolites due to lower enzyme activity, which leads to increased amounts of toxic metabolites and the development of III-IV acute GVHD. GSMT1*0 a single nucleotide polymorphism previously recognized as a risk factor for SOS was associated with a higher risk of SOS. We conclude that polymorphisms of genes involved in the metabolism of cyclophosphamide in our series are associated with severe grades of GVHD and toxicities (SOS and TRM) after haplo-HSCT and could be used to improve the clinical management of transplanted patients.
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