Skin biopsies for early diagnosis and prognosis of graft-versus-host disease in recipients of allogeneic stem cells from blood or bone marrow

Heldal, Dag; Brinch, Lorentz; Evensen, S A; Tjønnfjord, Geir E.; Aamodt, Geir; Elgjo, Kjell; Sviland, Lisbet

doi:10.1038/sj.bmt.1704568

Cited by 13 publications

(10 citation statements)

References 23 publications

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“…27,39,40 Most of the pathological alterations including infiltration of inflammatory cells into the skin, liver and large intestine and the presence of high numbers of apoptotic/necrotic cells in all tested organs were similar to those observed in irradiation-based aGVHD mouse models. [40][41][42] Our results confirm that the present model fulfils the criteria of aGVHD including histopathological changes.…”

Section: Discussionmentioning

confidence: 54%

GVHD after chemotherapy conditioning in allogeneic transplanted mice

Sadeghi

Aghdami

Hassan

et al. 2008

Bone Marrow Transplant

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GVHD is a major complication in allogeneic SCT. Available GVHD models are mainly based on radiotherapy-conditioning and/or immune deficient mice. GVHD models based on chemotherapy-based regimens remain poorly studied, despite 50% of all transplantations being chemotherapy based. Our aim was to develop a GVHD model using chemotherapy as conditioning. Female BALB/c (H-2Kd) were conditioned with BU-CY and transplanted with 2 Â 10 7 BM and 3 Â 10 7 spleen cells from either C57BL/6 (H-2 Kb) mice (allogeneic setting) or from male BALB/c to serve as a control group for regimen-related toxicity and engraftment. GVHD manifestations and histopathological changes were evaluated. Chimerism and donor T cells presence in skin, intestine and liver were studied using FACS-, FISH analysis and immunohistochemistry. Allogeneic transplanted mice developed lethal GVHD starting from day þ 7 with both histological and clinical signs. Donor T cells accumulated in recipient skin and intestine with GVHD progression. BM-failure, apoptosis and T-lymphocyte infiltration into target organs were significantly higher in allogeneic when compared with the syngeneic group. No toxicity or GVHD signs were observed in the syngeneic setting. We report a mouse model of GVHD using BU-CY conditioning that represents the most common myeloablativeconditioning regimen in clinical SCT. This model can be utilized to study the role of conditioning on mechanisms underlying GVHD.

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Section: Discussionmentioning

confidence: 54%

GVHD after chemotherapy conditioning in allogeneic transplanted mice

Sadeghi

Aghdami

Hassan

et al. 2008

Bone Marrow Transplant

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“…In addition, histopathological skin features seen in GVHD bearing mice such as increased apoptosis and inflammatory infiltration 31 reflect histology of cutaneous biopsies obtained from patients. 30,32,33 Interestingly, in acute GVHD survivors we observe in late phase a sclerotic thickening of the skin which is also seen in patients developing chronic GHVD.…”

Section: Discussionmentioning

confidence: 85%

A preclinical acute GVHD mouse model based on chemotherapy conditioning and MHC-matched transplantation

Riesner

Kalupa

Shi

et al. 2015

Bone Marrow Transplant

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Animal disease models have been criticized for lack of resemblance to human illnesses, hampering transfer of knowledge from preclinical research to clinical medicine. In the field of allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is standard practice to study GVHD in lethal TBI-based murine models. Frequently, MHC-mismatched donors are used in GVHD models. In contrast, in clinical allo-HSCT conditioning with chemotherapy (+/ − TBI) is common and donors are often MHC-matched. Aiming at a more clinically oriented situation, we established and characterized a murine MHC-matched, minor histocompatibility antigen mismatched GVHD model (LP/J [H2k b ] → C57BL/6 [H2k b ]) using busulfan and cyclophosphamide conditioning. We found typical clinical and histological features of acute GVHD. T-cell infiltration, GVHD-specific damage and systemic inflammation were similar to observations made in patients after allo-HSCT. In survivors of acute GVHD, we found expansion of CD4+ T cells and the development of scleroderma-like chronic GVHD. The use of chemotherapy-based, minor histocompatibility antigen (miHA)-mismatched GVHD animal models may be a good option when studying clinically relevant questions in the field of allo-HSCT.

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“…Furthermore, skin biopsies of a rather unspecific rash that occurs in the early phase after transplantation have been shown to be of limited value in predicting the progression from rash (viral-induced, drug-induced or early acute GVHD) to overt acute GVHD grade 2–4 irrespective of the stem cell source (peripheral blood, bone marrow). Likewise, the histopathological assessment of normal skin before allogeneic HSCT could not predict the development of GVHD [81, 84]. So far, in patients with clinicopathological acute GVHD, there are no known morphological or immunohistochemical features predicting the risk of subsequent chronic GVHD.…”

Section: Impact Of Histopathology In the Diagnosis And Prediction Of mentioning

confidence: 99%

“…Involvement of the upper portion of eccrine or follicular structures is a distinctive finding that often occurs early in the course of the disease and can prove helpful for diagnosis. Immunohistochemistry can identify the predominance of CD8+ lymphocytes as main effectors but its value in the diagnosis of acute GVHD is rather limited [81]. On a microscopic level, there is considerable overlap of histological findings of early GVHD and various other posttransplantation diseases (e.g.…”

Section: Impact Of Histopathology In the Diagnosis And Prediction Of mentioning

confidence: 99%

Cutaneous Graft-versus-Host Disease: A Guide for the Dermatologist

et al. 2008

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Graft-versus-host disease (GVHD) is defined by the aggregation of clinical and pathological manifestations in a recipient of allogeneic stem cells or bone marrow transplantation in which specific immunological as well as nonspecific phenomena lead to characteristic features. GVHD is one of the major complications after hematopoietic stem cell transplantations and responsible for posttherapeutic morbidity, mortality and decrease in quality of life of those patients. GVHD is critically induced and maintained by donor immunocompetent cells that particularly attack epithelia of fast proliferating tissues such as those from the liver, gastrointestinal tract and skin. On the basis of the time of presentation, cutaneous GVHD has been originally divided into an acute and chronic disease. The latter has traditionally been further subclassified into a more epithelial or lichenoid and a predominantly dermal or sclerodermoid form. With respect to the growing importance of this therapeutic procedure and increasing numbers of outpatients presenting with chronic GVHD, this article summarizes the updated knowledge on this disease focused for the dermatologist, and additionally it emphasizes the recent consensus documents on the various aspects of chronic GVHD of the National Institute of Health.

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Skin biopsies for early diagnosis and prognosis of graft-versus-host disease in recipients of allogeneic stem cells from blood or bone marrow

Cited by 13 publications

References 23 publications

GVHD after chemotherapy conditioning in allogeneic transplanted mice

GVHD after chemotherapy conditioning in allogeneic transplanted mice

A preclinical acute GVHD mouse model based on chemotherapy conditioning and MHC-matched transplantation

Cutaneous Graft-versus-Host Disease: A Guide for the Dermatologist

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