Effect of graft-versus-host disease on hematopoiesis after bone marrow transplantation in mice

Dijken, PJ van; Wimperis, JZ; Crawford, Julie M.; Ferrara, JL

doi:10.1182/blood.v78.10.2773.bloodjournal78102773

Cited by 4 publications

(2 citation statements)

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“…Possible mechanisms leading to low platelet counts in patients with GvHD may include reduced platelet production and increased consumption. The former has been shown in an animal model, in which acute GvHD reduced peripheral blood counts as well as the absolute number of donor stem cells, as identified by the spleen colony assay (van Dijken et al , 1991). It is also well‐known that negative regulators of haematopoiesis, such as tumour necrosis factor‐alpha, serum transforming growth factor‐beta1 and several cytokines, are released after allogeneic HSCT as a result of the conditioning regimen and graft‐vs.‐host disease (Hill et al , 1997; Liem et al , 1998, 1999).…”

Section: Discussionmentioning

confidence: 99%

Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft‐versus‐host disease, donor type, cytomegalovirus infections and cell dose

et al. 2001

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Platelet recovery after allogeneic haemopoietic stem cell transplant (HSCT) and predictive factors were analysed in 342 patients with haematological malignancies. All patients were prepared with cyclophosphamide plus total body irradiation, and received an unmanipulated HSCT from an HLA‐identical sibling (n = 270), a matched unrelated donor (n = 67) or an identical twin (n = 5). The source of stem cells was peripheral blood (n = 15) or bone marrow (n = 327). Graft‐vs.‐host disease (GvHD) prophylaxis consisted of cyclosporin A with or without methotrexate. The proportion of patients with < 50 × 109/l platelets on d +50, d +100, d +200 and d +365 after HSCT was 26%, 27%, 14% and 11% respectively. Thrombocytopenia was independent of the degree of complete donor chimaerism. Four variables were predictive of platelet recovery: donor type, acute GvHD, cytomegalovirus (CMV) infection and number of cells infused at transplant. Recipients of an unrelated graft had lower platelet counts (49 × 109/l) on d +50 than identical sibling grafts (108 × 109/l) (P < 0·001) and twin grafts (149 × 109/l) (P < 0·001). Patients with GvHD grades 0, I, II, III and IV had significantly different platelet counts on d +50 (153 × 109/l, 102 × 109/l, 85 × 109/l, 32 × 109/l and 22 × 109/l; P < 0·001) and thereafter. Thrombocytopenia was more frequent in patients with high‐level CMV antigenaemia (> four positive cells/2 × 105) (P < 0·0001) and in patients who received a low cell dose at transplant (≤ 4·1 × 108/kg) (P = 0·009). Platelet counts predicted transplant‐related mortality (TRM) and were higher at all time intervals in patients surviving the transplant. Patients with grade II GvHD and > 50 × 109/l platelets had a lower TRM than patients with grade II GvHD and ≤ 50 × 109/l platelets (14% vs. 40%, P < 0·0001). In conclusion, (i) a significant proportion of allogeneic HSCT recipients are thrombocytopenic long‐term, irrespective of complete donor chimaerism, (ii) thrombocytopenia identifies patients at greater risk of lethal complications, and (iii) platelet recovery is influenced by GvHD, donor type, CMV infections and cell dose, not by stem cell source or other patient–disease‐related variables.

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Section: Discussionmentioning

confidence: 99%

Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft‐versus‐host disease, donor type, cytomegalovirus infections and cell dose

et al. 2001

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“…Although target organs in aGVHD are typically limited to the skin, gut, and liver, aGVHD is often associated with systemic manifestations such as fever, impaired hematopoiesis ( 48 ), and immunosuppression ( 49 ). Therefore, not only the gut microbiome but also the blood metabolome may be involved in aGVHD pathogenesis.…”

Section: Resultsmentioning

confidence: 99%

Multi-omics Analysis of a Fecal Microbiota Transplantation Trial Identifies Novel Aspects of Acute GVHD Pathogenesis

Rashidi,

Ebadi,

Rehman

et al. 2024

Cancer Research Communications

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Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic cell transplantation (alloHCT) associated with gut microbiota disruptions. However, whether therapeutic microbiota modulation prevents aGVHD is unknown. We conducted a randomized, placebo-controlled trial of third-party fecal microbiota transplantation (FMT) administered at the peak of microbiota injury in 100 patients with acute myeloid leukemia receiving induction chemotherapy and alloHCT recipients. Despite improvements in microbiome diversity, expansion of commensals, and shrinkage of potential pathogens, aGVHD occurred more frequently after FMT than placebo. Although this unexpected finding could be explained by clinical differences between the two arms, we asked whether a microbiota explanation might be also present. To this end, we performed multi-omics analysis of pre- and post-intervention gut microbiome and serum metabolome. We found that post-intervention expansion of Faecalibacterium, a commensal genus with gut-protective and anti-inflammatory properties under homeostatic conditions, predicted a higher risk for aGVHD. Faecalibacterium expansion occurred predominantly after FMT and was due to engraftment of unique donor taxa, suggesting that donor Faecalibacterium-derived antigens might have stimulated allogeneic immune cells. Faecalibacterium and ursodeoxycholic acid (an anti-inflammatory secondary bile acid) were negatively correlated, offering an alternative mechanistic explanation. In conclusion, we demonstrate context dependence of microbiota effects where a normally beneficial bacteria may become detrimental in disease. While FMT is a broad, community-level intervention, it may need precision engineering in ecologically complex settings where multiple perturbations (e.g. antibiotics, intestinal damage, alloimmunity) are concurrently in effect.

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A Study of the Relationship of the Dynamics of Development and Characteristics of Chimerism with Manifestations of Graft-vs.-Host Disease in the Organs of Mice after Allogeneic Transplantation of Whole Bone Marrow

Bogdanenko,

Sergievich,

Karnaukhov

et al. 2024

Cell Tiss. Biol.

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Effect of graft-versus-host disease on hematopoiesis after bone marrow transplantation in mice

Cited by 4 publications

References 0 publications

Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft‐versus‐host disease, donor type, cytomegalovirus infections and cell dose

Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft‐versus‐host disease, donor type, cytomegalovirus infections and cell dose

Multi-omics Analysis of a Fecal Microbiota Transplantation Trial Identifies Novel Aspects of Acute GVHD Pathogenesis

A Study of the Relationship of the Dynamics of Development and Characteristics of Chimerism with Manifestations of Graft-vs.-Host Disease in the Organs of Mice after Allogeneic Transplantation of Whole Bone Marrow

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