Genomic instability after allogeneic hematopoietic cell transplantation is frequent in oral mucosa, particularly in patients with a history of chronic graft-versus-host disease, and rare in nasal mucosa

Khan, Faisal; Sy, Sarah; Louie, Polly; Ugarte-Torres, Alejandra; Berka, Noureddine; Sinclair, Gary D.; Stewart, Douglas A.; Russell, James A.; Storek, Jan

doi:10.1182/blood-2009-10-249201

Cited by 34 publications

(23 citation statements)

References 17 publications

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“…In an in vitro mutation analysis system, we found that allostimulated mixed lymphocyte cultures may induce MSI in co-cultured epithelial cells [22]. These results were independently confirmed by subsequent studies from other groups, which reported that the detection of MSI [23] and chromosomal instability [24] in the epithelial tissues of patients after allo-HSCT was correlated to the presence of GvHD inflammation.…”

Section: Introductionsupporting

confidence: 68%

DNA Damage and Repair in Epithelium after Allogeneic Hematopoietic Stem Cell Transplantation

Themeli

Spyridonidis

2012

IJMS

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in humans, following hematoablative treatment, results in biological chimeras. In this case, the transplanted hematopoietic, immune cells and their derivatives can be considered the donor genotype, while the other tissues are the recipient genotype. The first sequel, which has been recognized in the development of chimerical organisms after allo-HSCT, is the graft versus host (GvH) reaction, in which the new developed immune cells from the graft recognize the host’s epithelial cells as foreign and mount an inflammatory response to kill them. There is now accumulating evidence that this chronic inflammatory tissue stress may contribute to clinical consequences in the transplant recipient. It has been recently reported that host epithelial tissue acquire genomic alterations and display a mutator phenotype that may be linked to the occurrence of a GvH reaction. The current review discusses existing data on this recently discovered phenomenon and focuses on the possible pathogenesis, clinical significance and therapeutic implications.

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Section: Introductionsupporting

confidence: 68%

DNA Damage and Repair in Epithelium after Allogeneic Hematopoietic Stem Cell Transplantation

Themeli

Spyridonidis

2012

IJMS

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“…40 In addition, evidence suggests that chronic GVHD induces a chronic inflammatory state, leading to microsatellite instability and frequent genomic alterations in epithelial tissues, predisposing to development of cancers. 41,42 Several reports have shown increased risk of subsequent malignancy associated with chronic GVHD in FA.…”

Section: Discussionmentioning

confidence: 99%

Radiation-free, alternative-donor HCT for Fanconi anemia patients: results from a prospective multi-institutional study

Mehta

Davies

Leemhuis

et al. 2017

Blood

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• Alternative donor HCT can be performed in patients with FA without using radiation.• All 26 patients younger than 10 years of age undergoing HCT for marrow failure using lower-dose busulfancontaining regimen survived.Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by chromosomal fragility, progressive marrow failure, and cancer predisposition. Hematopoietic cell transplantation (HCT) is curative for FA-related marrow failure or leukemia, but both radiation exposure during transplant and graft-versus-host disease (GVHD) may increase risk of later malignancies of the head and neck and anogenital area. In this study, we tested a radiation-free conditioning regimen with a T-cell-depleted graft to eliminate radiation exposure and minimize early and late toxicities of transplant. Forty-five patients (median age, 8.2 years; range 4.3-44) with FA underwent HCT between June 2009 and May 2014. The preparative regimen included busulfan, cyclophosphamide, fludarabine, and rabbit anti-thymocyte globulin. Busulfan levels were monitored to avoid excess toxicity. All grafts were CD34-selected/T-cell-depleted using the CliniMacs CD34 columns (Miltenyi). Thirty-four patients (75.6%) with marrow failure and 11 (24.4%) with myelodysplastic syndrome underwent HCT using matched unrelated (n 5 25, 55.5%), mismatched unrelated (n 5 14, 31.1%), or mismatched related donors (n 5 6, 13.4%). One year probabilities of overall and disease-free survival for the entire cohort, including patients with myeloid malignancy and those receiving mismatched related/haploidentical grafts, were 80% (66%) and 77.7% (66.2%), respectively (median follow-up 41 months). All young children (<10 years of age) undergoing HCT for marrow failure using low-dose busulfancontaining regimen survived. No patients developed acute grade 3-4 GVHD. Sequential reduction of busulfan dose was successfully achieved per study design. Our results show excellent outcomes in patients with FA undergoing alternative donor HCT without radiation exposure. The study is registered to www.clinicaltrials.gov as #NCT01082133. (Blood. 2017;129(16):2308-2315

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“…Chronic GVHD was an independent risk factor for all solid cancers, and especially for cancers of the oral cavity. 34 The picture may also be different when it comes to some specific cancers such as thyroid cancer in which younger age was found to be the strongest risk factor of secondary thyroid cancer. 35 A joint EBMT/Seattle study showed that the cumulative incidence of breast cancer is around 5% at 20 years and the median time to breast cancer diagnosis is around 12.5 years.…”

Section: Late Secondary Malignancies After Allo-hsctmentioning

confidence: 99%

Long-term complications and side effects after allogeneic hematopoietic stem cell transplantation: an update

Mohty

2011

Blood Cancer Journal

162

124

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for various malignant and non-malignant diseases. Many patients have now been followed for two or three decades posttransplant and are presumed to be cured. With the tremendous advances achieved in terms of supportive care, it is reasonable to expect outcomes to improve steadily and consequently increasing numbers of transplant survivors will be facing life after the initial transplant experience. Although long-term allo-HSCT survivors generally enjoy good health, for many others, cure or control of the underlying disease is not accompanied by full restoration of health. The burden of long-term morbidity borne by allo-HSCT survivors is substantial, and long-term follow-up of patients who received allo-HSCT is now widely recommended. Immediate survival is no longer the sole concern after allo-HSCT. The goals should also include complete recovery of the overall health status with normal physical and psychological functioning. Long-term side effects after allo-HSCT include non-malignant organ or tissue dysfunction, changes in quality of life, infections related to abnormal immune reconstitution and secondary cancers. Many of these can be attributed to the deleterious effects of chronic graft-versus-host disease. The aims of this review are to provide an update on the recent research evidence in the field.

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Genomic instability after allogeneic hematopoietic cell transplantation is frequent in oral mucosa, particularly in patients with a history of chronic graft-versus-host disease, and rare in nasal mucosa

Cited by 34 publications

References 17 publications

DNA Damage and Repair in Epithelium after Allogeneic Hematopoietic Stem Cell Transplantation

DNA Damage and Repair in Epithelium after Allogeneic Hematopoietic Stem Cell Transplantation

Radiation-free, alternative-donor HCT for Fanconi anemia patients: results from a prospective multi-institutional study

Long-term complications and side effects after allogeneic hematopoietic stem cell transplantation: an update

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