Chimerism Monitoring Techniques after Hematopoietic Stem Cell Transplantation: An Overview of the Last 15 Years of Innovations

Tozzo, Pamela; Delicati, Arianna; Zambello, Renato; Caenazzo, Luciana

doi:10.3390/diagnostics11040621

Cited by 25 publications

(28 citation statements)

References 57 publications

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“…Regarding SNP-qPCR methods, it has been reported that using < 10 markers results in 80%-97% informativity, suggesting the need for a larger set of markers [13,20]. Additionally, uorescence in situ hybridization with sex chromosomes is usable only for sex-mismatched donor/recipient pairs [4]. Therefore, the high informativity of premixed markers may be an advantage of the KMR kits.…”

Section: Discussionmentioning

confidence: 99%

“…Chimerism analysis assesses proportions of hematopoietic cells from the donor (donor chimerism) and recipient (recipient chimerism), and it is used as a con rmation of engraftment and as a surrogate indicator for graft rejection or relapse [4,5]. The major techniques of chimerism analysis are PCR for short tandem repeat (STR) pro les of DNA (STR-PCR), and detection of single nucleotide polymorphisms (SNPs) with real-time quantitative PCR (qPCR)-based methods (SNP-qPCR) [4][5][6][7]. Although STR-PCR is the predominant method, technical variability among laboratories is pronounced, and the detection limit for recipient chimerism is not very low, ranging from 1-10% among studies [7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Although STR-PCR is the predominant method, technical variability among laboratories is pronounced, and the detection limit for recipient chimerism is not very low, ranging from 1-10% among studies [7][8][9][10][11][12][13]. SNP-qPCR is a fast and sensitive method to detect recipient chimerism below 1%, but there are issues such as limited informativity, inconsistent quantitative accuracy, false positive results, and technical variations [4,12]. Thus, chimerism analysis lacks methodological standardization and might not discriminate between donor and recipient cells with su cient reliability [4-7, 12, 13].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of a quantitative PCR-based method for chimerism analysis of Japanese donor/recipient pairs

Ikeda

Minakawa

Ono

et al. 2022

Preprint

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Chimerism analysis is a surrogate indicator of graft rejection or relapse after allogeneic hematopoietic stem cell transplantation (HSCT). Although short tandem repeat PCR (STR-PCR) is the usual method, limited sensitivity and technical variability are matters of concern. Quantitative PCR-based methods to detect single nucleotide polymorphisms (SNP-qPCR) are more sensitive, but their informativity and quantitative accuracy are highly variable. For accurate and sensitive chimerism analysis, a set of KMR kits (GenDx, Utrecht, Netherlands), based on detection of insertions/deletions (indels) by qPCR, have been developed. Here, we investigated informativity and validated the accuracy of KMR kits in Japanese donor/recipient pairs and virtual samples of DNA mixtures representative of Japanese genetic diversity. We found that at least one recipient-specific marker among 39 KMR-kit markers was informative in all of 65 Japanese donor/recipient pairs. Moreover, the percentage of recipient chimerism estimated by KMRtrack correlated well with ratios of mixed DNA in virtual samples and with the percentage of chimerism in HSCT recipients estimated by STR-PCR/in-house SNP-qPCR. Moreover, KMRtrack showed better sensitivity with high specificity when compared to STR-PCR to detect recipient chimerism. Chimerism analysis with KMR kits can be a standardized, sensitive, and highly informative method to evaluate the graft status of HSCT recipients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of a quantitative PCR-based method for chimerism analysis of Japanese donor/recipient pairs

Ikeda

Minakawa

Ono

et al. 2022

Preprint

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“…Sampling and methylation analysis Methylation analysis of DNA obtained from peripheral blood nucleated cells was performed in 54 cases after cord blood transplantation. Among them, chimerism analysis between donors and recipients was performed by the short tandem repeat (STR) method; 50 recipients and 95% of donors were subjected to analysis 12 . Transplant information for the 50 cases is shown in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Donor cord blood aging accelerates in recipients after transplantation

Onizuka

Imanishi

Harada

et al. 2022

Preprint

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Cord blood stem cell transplantation is an important alternative for patients needing hematopoietic stem cell transplantation. However, it is unclear how cord blood cells, which are 0-year-old, age in the recipient’s body after allogeneic transplantation. We performed DNA methylation (DNAm) age analysis to measure the age of cells using post-transplant peripheral blood in 50 cases of cord blood transplantation. The median chronological age (the time elapsed from the date of the cord blood transplant to the day the sample was taken for DNAm analysis) of donor cells was 4.0 years (0.2 – 15.0 years), while the median DNAm age was 10.0 years (1.3 – 30.3 years), and the ratio of DNAm age to chronological age (AgeAccel) was 2.7 (1.2 – 8.2). When comparing the mean values of AgeAccel in cord blood transplant cases and controls, the values were significantly higher in cord blood transplant cases. The characteristics of patients and transplant procedures were not associated with AgeAccel in this analysis, nor were they associated with the development of graft-versus-host disease. However, this analysis revealed that transplanting 0-year-old cord blood into a recipient resulted in cells aging more than twice as quickly as the elapsed time. The results shed light on the importance of the mismatch between cord blood stem cells and donor environmental factors in stem cell aging.

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“…Human chimerism is the presence of more than one population of genetically differentiated cells in an individual. This genetic condition can be acquired through transfusion or transplantation of cells from a donor to the patient, it can also be congenital, resulting from fusion of individual dizygotic embryos or by double-embryonic embryo transfer (Tozzo et al, 2021;Johnson et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Laboratory diagnosis for human chimerism: systematic review

Weber

Rocha

Nogueira

et al. 2022

RSD

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The objective of the article was to perform a systematic review of the literature on laboratory diagnosis for human chimerism. The Medical Literature Analysis and Retrieval System Online (Medline), Public Medline or Publisher Medline (PubMed), Scientific Electronic Library (Scielo), Latin American and Caribbean Literature on Health Sciences (LILACS) databases were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Articles were included that had as an endpoint evidencing the diagnosis for chimerism in humans, published in the period from 2005 to 2018. Articles whose endpoint was the occurrence of other types of chimerism were excluded. To compose the study, 36 articles were pre-selected, of these only 6 met the inclusion criteria given by the PRISMA method. Regarding the diagnostics used in the articles to detect chimerism, in 100% of the articles there is reference to the Polymerase Chain Reaction (PCR) combined with other techniques as the main diagnostic for detection of chimerism, such as Fluorescent in situ hybridization (FISH), Short Tandem Repeats (STR), Single Nucleotide Polymorphisms (SNPs), Small Insertions and Deletions (INDELs), Single Molecular Inversion Molecular Probes (smMIP) and TaqMan type molecular probes. These combined techniques have many advantages and are decisive for the scientific community in revealing this genetic condition. Thus, it is concluded that there are few techniques that allow a specific diagnosis for chimerism, however, the existing techniques are effective in identifying this genetic condition.

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Chimerism Monitoring Techniques after Hematopoietic Stem Cell Transplantation: An Overview of the Last 15 Years of Innovations

Cited by 25 publications

References 57 publications

Evaluation of a quantitative PCR-based method for chimerism analysis of Japanese donor/recipient pairs

Evaluation of a quantitative PCR-based method for chimerism analysis of Japanese donor/recipient pairs

Donor cord blood aging accelerates in recipients after transplantation

Laboratory diagnosis for human chimerism: systematic review

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