Recommendations for (Pharmaco)Genetic Sampling in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation

ABSTRACT In patients receiving allogenic hematopoietic stem cell transplantation (aHSCT) complete chimerism is desired. However, this brings a challenge when non‐invasive assessment of recipient germline DNA is required for genetic testing. Here, we aim to create awareness for (pharmaco)genetic samp...

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Main Authors: Anniek Bokma, Maja Matic, Arwin Ralf, Bianca J. C. vanden Bosch, Manfred Kayser, Ron H. N. vanSchaik, Melvin Lafeber, Marieke J. H. Coenen, Florence Atrafi
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Clinical and Translational Science
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Online Access:https://doi.org/10.1111/cts.70303
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author Anniek Bokma
Maja Matic
Arwin Ralf
Bianca J. C. vanden Bosch
Manfred Kayser
Ron H. N. vanSchaik
Melvin Lafeber
Marieke J. H. Coenen
Florence Atrafi
author_facet Anniek Bokma
Maja Matic
Arwin Ralf
Bianca J. C. vanden Bosch
Manfred Kayser
Ron H. N. vanSchaik
Melvin Lafeber
Marieke J. H. Coenen
Florence Atrafi
author_sort Anniek Bokma
collection DOAJ
description ABSTRACT In patients receiving allogenic hematopoietic stem cell transplantation (aHSCT) complete chimerism is desired. However, this brings a challenge when non‐invasive assessment of recipient germline DNA is required for genetic testing. Here, we aim to create awareness for (pharmaco)genetic sampling in patients following aHSCT based on a case report of a patient following aHSCT in which pharmacogenetic analysis was performed. Six pharmacogenetic genes were analyzed in DNA extracted from peripheral blood (pre‐ and post‐transplant), buccal swab, and hair follicles. To investigate the presence of donor DNA in post‐transplant samples, short tandem repeat and digital droplet PCR analysis were performed. DNA from post‐transplantation peripheral blood and the buccal swab showed identical genotypes: CYP2C9*1/*1, CYP2C19*1/*2, CYP2D6*2/*9, CYP3A4*1/*1, VKORC1‐1639TT, SLCO1B1*1/*5. Pre‐transplant DNA showed different genotypes for CYP2D6 (*1/*2) and SLCO1B1 (*1/*1). Due to the low DNA amount extracted from hair follicles, only CYP2D6 and SLCO1B1 were examined, showing identical genotypes to pre‐transplantation DNA. Short tandem repeat analysis showed that the buccal swab contained DNA from both donor and recipient. It was estimated that the buccal swab contained ~63% donor DNA, while DNA from hair follicles showed 0% donor DNA. In conclusion, pharmacogenetic profiling after allogenic HSCT should be done with consideration. Analysis of pre‐transplant peripheral blood is preferred over buccal swab due to the presence of donor DNA contamination. DNA extracted from hair is also a reliable source; however, application might be restricted due to limited DNA yield.
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spelling doaj-art-e249b6c235f5441fb97adbc75ab492152025-08-23T17:10:42ZengWileyClinical and Translational Science1752-80541752-80622025-08-01188n/an/a10.1111/cts.70303Recommendations for (Pharmaco)Genetic Sampling in Patients Following Allogeneic Hematopoietic Stem Cell TransplantationAnniek Bokma0Maja Matic1Arwin Ralf2Bianca J. C. vanden Bosch3Manfred Kayser4Ron H. N. vanSchaik5Melvin Lafeber6Marieke J. H. Coenen7Florence Atrafi8Department of Internal Medicine, Division of Vascular Medicine and Pharmacology Erasmus MC University Medical Center Rotterdam the NetherlandsDepartment of Clinical Chemistry Erasmus MC University Medical Centre Rotterdam the NetherlandsDepartment of Genetic Identification Erasmus MC University Medical Center Rotterdam the NetherlandsDepartment of Clinical Genetics Maastricht University Medical Center+ Maastricht the NetherlandsDepartment of Genetic Identification Erasmus MC University Medical Center Rotterdam the NetherlandsDepartment of Clinical Chemistry Erasmus MC University Medical Centre Rotterdam the NetherlandsDepartment of Internal Medicine, Division of Vascular Medicine and Pharmacology Erasmus MC University Medical Center Rotterdam the NetherlandsDepartment of Clinical Chemistry Erasmus MC University Medical Centre Rotterdam the NetherlandsDepartment of Internal Medicine, Division of Vascular Medicine and Pharmacology Erasmus MC University Medical Center Rotterdam the NetherlandsABSTRACT In patients receiving allogenic hematopoietic stem cell transplantation (aHSCT) complete chimerism is desired. However, this brings a challenge when non‐invasive assessment of recipient germline DNA is required for genetic testing. Here, we aim to create awareness for (pharmaco)genetic sampling in patients following aHSCT based on a case report of a patient following aHSCT in which pharmacogenetic analysis was performed. Six pharmacogenetic genes were analyzed in DNA extracted from peripheral blood (pre‐ and post‐transplant), buccal swab, and hair follicles. To investigate the presence of donor DNA in post‐transplant samples, short tandem repeat and digital droplet PCR analysis were performed. DNA from post‐transplantation peripheral blood and the buccal swab showed identical genotypes: CYP2C9*1/*1, CYP2C19*1/*2, CYP2D6*2/*9, CYP3A4*1/*1, VKORC1‐1639TT, SLCO1B1*1/*5. Pre‐transplant DNA showed different genotypes for CYP2D6 (*1/*2) and SLCO1B1 (*1/*1). Due to the low DNA amount extracted from hair follicles, only CYP2D6 and SLCO1B1 were examined, showing identical genotypes to pre‐transplantation DNA. Short tandem repeat analysis showed that the buccal swab contained DNA from both donor and recipient. It was estimated that the buccal swab contained ~63% donor DNA, while DNA from hair follicles showed 0% donor DNA. In conclusion, pharmacogenetic profiling after allogenic HSCT should be done with consideration. Analysis of pre‐transplant peripheral blood is preferred over buccal swab due to the presence of donor DNA contamination. DNA extracted from hair is also a reliable source; however, application might be restricted due to limited DNA yield.https://doi.org/10.1111/cts.70303allogeneicbuccalhairhematopoietic stem cell transplantationpharmacogeneticssaliva
spellingShingle Anniek Bokma
Maja Matic
Arwin Ralf
Bianca J. C. vanden Bosch
Manfred Kayser
Ron H. N. vanSchaik
Melvin Lafeber
Marieke J. H. Coenen
Florence Atrafi
Recommendations for (Pharmaco)Genetic Sampling in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation
Clinical and Translational Science
allogeneic
buccal
hair
hematopoietic stem cell transplantation
pharmacogenetics
saliva
title Recommendations for (Pharmaco)Genetic Sampling in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation
title_full Recommendations for (Pharmaco)Genetic Sampling in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation
title_fullStr Recommendations for (Pharmaco)Genetic Sampling in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation
title_full_unstemmed Recommendations for (Pharmaco)Genetic Sampling in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation
title_short Recommendations for (Pharmaco)Genetic Sampling in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation
title_sort recommendations for pharmaco genetic sampling in patients following allogeneic hematopoietic stem cell transplantation
topic allogeneic
buccal
hair
hematopoietic stem cell transplantation
pharmacogenetics
saliva
url https://doi.org/10.1111/cts.70303
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AT biancajcvandenbosch recommendationsforpharmacogeneticsamplinginpatientsfollowingallogeneichematopoieticstemcelltransplantation
AT manfredkayser recommendationsforpharmacogeneticsamplinginpatientsfollowingallogeneichematopoieticstemcelltransplantation
AT ronhnvanschaik recommendationsforpharmacogeneticsamplinginpatientsfollowingallogeneichematopoieticstemcelltransplantation
AT melvinlafeber recommendationsforpharmacogeneticsamplinginpatientsfollowingallogeneichematopoieticstemcelltransplantation
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