DNA chimerism and its consequences after allogeneic hematopoietic cell transplantation

Themeli, Maria; Waterhouse, Miguele; Finke, Juergen; Spyridonidis, Alexandros

doi:10.4161/chim.15276

Cited by 11 publications

(3 citation statements)

References 29 publications

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“…Recently, it has been suggested that after allo HSCT, donor cells undergoing apoptosis release donor DNA packaged apoptotic bodies that are engulfed by the host epithelium and the donor-derived genome is integrated inside nuclei of host epithelium via horizontal DNA transfer hence leading to epithelial chimerism and related genomic instabilities. 22 The exact mechanisms underlying emergence of host epithelial cells with donor genotype are unclear and remain divergent.…”

Section: Discussionmentioning

confidence: 99%

Utility of saliva and hair follicles in donor selection for hematopoietic stem cell transplantation and chimerism monitoring

et al. 2012

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Selection of an HLA identical donor is a critical pre-requisite for successful hematopoietic stem cell transplantation (HSCT). Most transplant centers utilize blood as the most common source of DNA for HLA testing. However, obtaining blood through phlebotomy is often challenging in patients with conditions like severe leucopenia or hemophilia, pediatric and elderly patients. We have used a simple in-house protocol and shown that HLA genotypes obtained on DNA extracted from saliva or hair are concordant with blood and hence can be used for selection of donors for HSCT or organ transplantation. Similarly, for post-HSCT chimerism monitoring, non-availability of pre-transplant DNA samples poses a major limitation of reference STR fingerprints. This study shows that DNA obtained post-HSCT from hair follicles can be used to generate pre-transplant patient specific fingerprints while the STR profiles obtained in saliva samples cannot as these display a mixed state of chimerism.

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Section: Discussionmentioning

confidence: 99%

Utility of saliva and hair follicles in donor selection for hematopoietic stem cell transplantation and chimerism monitoring

et al. 2012

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“…When dealing with a young patient with TNBC, genetic testing is of great importance, due to the fact that up to 40% of the early-onset and/or familial TNBC have germline pathogenic variants in BRCA1 , BRCA2 , PALB2 , and some other genes ( 32 ). Accordingly, our patient was referred to a geneticist, but since she was an allo-SCT recipient, and her mother was a donor, choosing the most appropriate and reliable biological sample for genetic testing proved difficult ( 33 , 34 ). After the allo-SCT, not only blood cells but also other cell subtypes may be replaced by cells of donors’ origin during a process called adult stem cell plasticity phenomenon ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Challenges in the management of operable triple-negative breast cancer in a survivor of the B-cell acute lymphoblastic leukemia: a case report

Pavlin,

Blatnik,

Šeruga

2024

Front. Oncol.

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BackgroundOperable triple-negative breast cancer (TNBC) is an unfavorable subtype of breast cancer, which usually requires an aggressive perioperative systemic treatment. When TNBC presents as a second primary cancer after cured acute leukemia, its management might be challenging.Case presentationWe present a case report of a young postmenopausal woman with an operable TNBC who had a history of the B-cell acute lymphoblastic leukemia (B-ALL) and graft versus host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). A history of previous treatment with anthracyclines and radiotherapy and GVHD limited the use of doxorubicin for treatment of her TNBC. Due to the history of GVHD, perioperative treatment with pembrolizumab was omitted. Genetic testing was challenging due to the possible contamination of her tissues with the donor’s cells after allo-SCT. In samples of our patient’s buccal swab, peripheral blood, and tumor tissue, a pathogenic variant in the partner and localizer of BRCA2 (PALB2) gene was found. With neoadjuvant chemotherapy which included carboplatin, a pathologic complete response was achieved. Although our patient has a low risk for recurrence of TNBC, her risk for the development of new primary cancers remains substantial.ConclusionThis case highlights challenges in the systemic treatment, genetic testing, and follow-up of patients with operable TNBC and other solid cancers who have a history of acute leukemia.

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“…The net effect of this allo-antigenic reaction is tissue stress and apoptosis, which is known as graft vs host disease. Chronic stress due to interaction of donor derived lymphocytes with host epithelium in the biological chimera may cause genomic alteration ( 28 ). Hence, the development of epithelial cells with donor derived genotype and the accumulation of genomic alterations in the epithelial tissue are the recognized phenomena occurring in the recipient after allo-HSCT, explaining the presence of donor derived DNA in recipient epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of blood, buccal swabs, and hair follicles for DNA profiling technique using STR markers

2015

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AimTo study the short tandem repeat (STR) pattern of DNA from the blood, buccal swabs, and hair follicles of the recipients of allogenic hematopoietic stem cell transplantation to examine whether these tissues contain donor derived cells.MethodsThe study enrolled 25 patients who sustained engraftment. Peripheral blood, buccal swabs, and hair follicles were collected on days 21-30, 90, and 180 after transplantation and the chimeric status of the recipients was evaluated.ResultsDonor derived cells existed in the blood and buccal swabs, but not in hair follicles, which can be used to obtain the pre-transplant sample of the recipient after transplant.ConclusionPeripheral blood and buccal swab do not serve as a reliable source of recipient’s origin for DNA analysis of individuals who underwent allogenic hematopoietic stem cell transplantation at least within 6 months after transplant.

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DNA chimerism and its consequences after allogeneic hematopoietic cell transplantation

Cited by 11 publications

References 29 publications

Utility of saliva and hair follicles in donor selection for hematopoietic stem cell transplantation and chimerism monitoring

Utility of saliva and hair follicles in donor selection for hematopoietic stem cell transplantation and chimerism monitoring

Challenges in the management of operable triple-negative breast cancer in a survivor of the B-cell acute lymphoblastic leukemia: a case report

Evaluation of blood, buccal swabs, and hair follicles for DNA profiling technique using STR markers

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