CD34+ chimerism analysis for minimal residual disease monitoring after allogeneic hematopoietic cell transplantation

Unnikrishnan, Athira; Meacham, Amy; Goldstein, Steven; Ta, Mai; Leather, Helen; Cogle, Christopher R.; Castillo, Paul; Wingard, John R.; Norkin, Maxim

doi:10.1016/j.leukres.2018.10.007

Cited by 6 publications

(5 citation statements)

References 5 publications

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“…43,58 When testing bone marrow, isolating and analysing CD34 + cells offers valuable information about the level of stem cell engraftment. Unnikrishnan et al (2018) showed that a decrease in the donor chimaerism within the CD34 + stem cell compartment of less than 80% had 100% sensitivity in predicting disease relapse. 59 In patients transplanted for B-cell ALL, CD19, CD20 or CD22 might be more appropriate targets if they are LAIPassociated markers.…”

Section: Haematological Malignanciesmentioning

confidence: 99%

The significance of mixed chimaerism and cell lineage chimaerism monitoring in paediatric patients post haematopoietic stem cell transplant

2022

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Haematopoietic stem cell transplants (HSCTs) are carried out across the world to treat haematological and immunological diseases which would otherwise prove fatal. Certain diseases are predominantly encountered in paediatric patients, such severe primary immunodeficiencies (PID) and diseases of inborn errors of metabolism (IEM). Chimaerism testing for these disorders has different considerations compared to adult diseases. This review focuses on the importance of cell-lineagespecific chimaerism testing and examines the appropriate cell populations to be assessed in individual paediatric patient groups. By analysing disease-associated subpopulations, abnormalities are identified significantly earlier than in whole samples and targeted clinical decisions can be made. Chimaerism methods have evolved over time and lead to an ever-increasing level of sensitivity and biomarker arrays to distinguish between recipient and donor cells. Short tandem repeat (STR) is still the gold standard for routine chimaerism assessment, and hypersensitive methods such as quantitative and digital polymerase chain reaction (PCR) are leading the forefront of microchimaerism testing. The rise of molecular methods operating with minute DNA amounts has been hugely beneficial to chimaerism testing of paediatric samples. As HSCTs are becoming increasingly personalised and risk-adjusted towards a child's individual needs, chimaerism testing needs to adapt alongside these medical advances ensuring the best possible care.How to cite this article: Kricke S, Rao K, Adams S. The significance of mixed chimaerism and cell lineage chimaerism monitoring in paediatric patients post haematopoietic stem cell transplant.

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Section: Haematological Malignanciesmentioning

confidence: 99%

The significance of mixed chimaerism and cell lineage chimaerism monitoring in paediatric patients post haematopoietic stem cell transplant

2022

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“…CD34 is expressed on the majority of blast cells in AML, MDS and ALL populations and can be used in in these patient populations as a more sensitive predictor of disease relapse compared to whole blood chimerism, especially in the absence of a disease-specific MRD marker [57][58][59][60][61]. Unnikrishnan et al [60] were able to show that a CD34+ donor chimerism of <80% could predict relapse with a sensitivity of 100% and specificity of 67%, compared to 14% and 83% for donor chimerism on whole blood (based on a population of 13 patients, 7 of which relapsed post-HSCT). Similarly, Hoffman et al [61] showed that a CD34+ donor chimerism of <80% had a 100% sensitivity for prediction of relapse.…”

Section: Cd34+ Chimerismmentioning

confidence: 99%

“…Based on the available evidence, a decline in CD34 + donor chimerism occurs earlier prior to relapse compared to a decline in peripheral whole blood chimerism [58][59][60][61]. In the patients studied by Urrikrishnan et al [60] who showed hematological relapse, a decline of CD34+ donor chimerism could be documented at a median of 69 days prior to documentation of relapse (with a range of 4-175 days) and in the population studied by Thiede et al [58] a decline in CD34+ donor chimerism could be detected 12-97 days prior to clinical relapse in 20/22 patients.…”

Section: Cd34+ Chimerismmentioning

confidence: 99%

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Use of chimerism analysis after allogeneic stem cell transplantation: Belgian guidelines and review of the current literature

Delie

Verlinden

Beel

et al. 2020

Acta Clinica Belgica

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Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option in both adult and pediatric patients with malignant and non-malignant hematological diseases. Chimerism analysis, which determines the donor or recipient origin of hematopoietic cells in HSCT recipients, is an essential aspect of post-HSCT follow-up. Objectives: To review the current literature and develop Belgian consensus guidelines for the use of chimerism analysis in the standard of care after allogeneic HSCT. Methods: Non-systematic review of the literature in consultancy with the members of the BHS transplantation committee. Results: Clinical application with regards to prediction of graft failure or relapse as well as cell source are reviewed. A consensus guideline on the use of chimerism analysis after HSCT is presented. Conclusion: Monitoring of the dynamics or kinetics of a patient's chimerism status by serial analysis at fixed time points, as well as on suspicion of relapse or graft failure, is needed to monitor engraftment levels, as well as disease control and possible relapse.

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“…Lineage-specific chimerism analysis may increase the specificity in predicting relapse (114). A prospective study found that the decrease of CD34 + -specific donor chimerism to <80% had 100% sensitivity and 86% accuracy in predicting relapse (84). T lymphocyte chimerism ≤85% at days 90 and 120 after allo-HSCT was shown to predict relapse for patients who were in first/second complete remission at transplantation (85).…”

Section: Chimerismmentioning

confidence: 99%

Novel Biomarkers for Outcome After Allogeneic Hematopoietic Stem Cell Transplantation

Chen

Zeiser

2020

Front. Immunol.

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a well-established curative treatment for various malignant hematological diseases. However, its clinical success is substantially limited by major complications including graft-vs.-host disease (GVHD) and relapse of the underlying disease. Although these complications are known to lead to significant morbidity and mortality, standardized pathways for risk stratification of patients undergoing allo-HSCT are lacking. Recent advances in the development of diagnostic and prognostic tools have allowed the identification of biomarkers in order to predict outcome after allo-HSCT. This review will provide a summary of clinically relevant biomarkers that have been studied to predict the development of acute GVHD, the responsiveness of affected patients to immunosuppressive treatment and the risk of non-relapse mortality. Furthermore, biomarkers associated with increased risk of relapse and subsequent mortality will be discussed.

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CD34+ chimerism analysis for minimal residual disease monitoring after allogeneic hematopoietic cell transplantation

Cited by 6 publications

References 5 publications

The significance of mixed chimaerism and cell lineage chimaerism monitoring in paediatric patients post haematopoietic stem cell transplant

The significance of mixed chimaerism and cell lineage chimaerism monitoring in paediatric patients post haematopoietic stem cell transplant

Use of chimerism analysis after allogeneic stem cell transplantation: Belgian guidelines and review of the current literature

Novel Biomarkers for Outcome After Allogeneic Hematopoietic Stem Cell Transplantation

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