A European Multicenter Study of Chronic Graft-Versus-Host Disease

Boström, Lars; Ringdén, Olle; Jacobsen, N; Zwaan, F. E.; Nilsson, Birgitta

doi:10.1097/00007890-199006000-00014

Cited by 53 publications

(7 citation statements)

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“…However, this did not account for the increased risk of chronic GVHD in the latter group because CMV serology showed no relation to chronic GVHD in this study. This is in contrast to previous studies which found a correlation between CMV serology and chronic GVHD (30). In these previous studies, ethnic origin was not addressed.…”

Section: Discussioncontrasting

confidence: 99%

An ethnic role for chronic, but not acute, graft‐versus‐host disease after HLA‐identical sibling stem cell transplantation

Remberger

Aschan²,

Lönnqvist³

et al. 2001

European J of Haematology

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Among 424 HLA identical siblings undergoing stem cell transplantation, 364 were Scandinavians and 60 represented other ethnic groups. The cumulative probabilities of acute graft-versus-host disease grades II-IV were similar in both groups, 17% in Scandinavians and 12% in the others, p = 0.4. In a multivariate analysis, less effective immune suppression with cyclosporine or methotrexate alone (p = 0.001), recipient seropositive for three to four herpes viruses (p = 0.004), CMV-seropositive recipient (p = 0.05) and early engraftment (before day 15) (p = 0.05) were independent risk-factors for acute GVHD grades II-IV. The cumulative probabilities of chronic GVHD were 47% and 68% in the two ethnic populations, respectively (p = 0.004). In multivariate analysis, higher patient age (p < 0.001), non-Scandinavian population (p < 0.001) and immunised female donor to male recipient (p = 0.03) were independent risk factors for chronic GVHD. The higher incidence of chronic GVHD could not be explained by differences in HLA antigen frequencies. The cumulative probabilities of relapse were 37% in the both groups. This suggests that the Scandinavian population is more homogeneous with regard to minor histocompatibility antigens important for chronic, but not acute GVHD.

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Section: Discussioncontrasting

confidence: 99%

An ethnic role for chronic, but not acute, graft‐versus‐host disease after HLA‐identical sibling stem cell transplantation

Remberger

Aschan²,

Lönnqvist³

et al. 2001

European J of Haematology

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“…A previous study from our center showed a correlation between CMV infection and development of chronic GVHD [52], but a more recent report showed no such correlation [39]. An experimental study showed a correlation between CMV infection and development of severe chronic GVHD [53].…”

Section: B B and M Tmentioning

confidence: 78%

“…Among patients who developed chronic GVHD, previous acute GVHD grades II to IV was the only predictive factor for development of moderate-to-severe versus mild disease. Many other studies have shown that acute GVHD is a risk factor for the development of chronic GVHD [5][6][7]38,39). One could therefore assume that more severe forms of acute GVHD may lead to more severe forms of chronic GVHD.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for moderate-to-severe chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Remberger

Kumlien

Aschan

et al. 2002

Biology of Blood and Marrow Transplantation

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Among 810 consecutive hematopoietic stem cell transplantation (HSCT) patients, 679 survived more than 3 months and were evaluated for chronic GVHD. The aim of this study was to find predisposing factors increasing the risk of development of moderate-to-severe chronic GVHD. Many of the donors were HLA-identical siblings or related (n = 435), 185 were HLA-matched unrelated, and 59 were mismatched related or unrelated donors. Most of the patients had a hematological malignancy (n = 568), but 111 patients with a nonmalignant disease were included. Two hundred twenty-three patients (33%) developed mild, 41 (6%) moderate, and 15 (2.2%) severe chronic GVHD. The 5-year probability of development of moderate-to-severe chronic GVHD was 10%. We analyzed 30 potential risk factors for chronic GVHD. In the multivariate analysis, acute GVHD) grades II to IV (relative hazard [RH], 2.30; 95% CI, 1.29-4.10; P = .005), CML diagnosis (RH, 2.37; CI, 1.38-4.08; P = .002) and transplantation from an immunized female donor to a male recipient (RH, 2.16; CI, 1.14-4.11; P = .02) were independent risk factors for moderate-to-severe chronic GVHD. Recipient age also was significant (RH, 2.42; CI, 1.23-4.77; P = .01) if CML was not included in the analysis. In patients with no risk factors, the 5-year probability of development of moderate-to-severe chronic GVHD was 5%. In patients with 1 risk factor, the probability was 13%; 2 risk factors, 23%; and 3 risk factors, 45%. Among patients who developed chronic GVHD (n = 279), acute GVHD grades II to IV (RH, 2.18; CI, 1.23-3.86; P < .01) was the only predictive factor for moderate-to-severe chronic GVHD versus mild disease. Patients with previous acute GVHD grades II to IV may benefit from more aggressive initial treatment. This possibility would have to be examined in clinical trials.

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“…In clinical settings, reactivation of HCMV has long been associated with sepsis and other systemic inflammatory conditions in patients who are not immunosuppressed (Docke et al, 1994;Cook et al, 1998;Kutza et al, 1998;Heininger et al, 2001;Limaye et al, 2008;Kalil and Florescu, 2009;Walton et al, 2014), with allograft rejection in immunosuppressed recipients of solid organ transplants (Grattan et al, 1989;Reinke et al, 1994;Lao et al, 1997;Lautenschlager et al, 1997;Evans et al, 2001;Razonable et al, 2001;Nett et al, 2004;Dmitrienko et al, 2009), and with graft vs. host disease in stem cell transplant recipients (Lonnqvist et al, 1984;Meyers et al, 1986;Bostrom et al, 1990;Matthes-Martin et al, 1998;Broers et al, 2000;Boeckh and Nichols, 2004). Treatment with antilymphocyte antibodies, which is often used to control rejection of solid organs, is a known risk factor for reactivation of CMV (Hibberd et al, 1992;Fietze et al, 1994;Portela et al, 1995).…”

Section: Reactivation Of Naturally Acquired Hcmv Infectionmentioning

confidence: 99%

Cytomegalovirus Latency and Reactivation: An Intricate Interplay With the Host Immune Response

Forte

Zhang

Thorp

et al. 2020

Front. Cell. Infect. Microbiol.

152

103

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CMV is an ancient herpesvirus that has co-evolved with its host over millions of years. The 236 kbp genome encodes at least 165 genes, four non-coding RNAs and 14 miRNAs. Of the protein-coding genes, 43-44 are core replication genes common to all herpesviruses, while ∼30 are unique to betaherpesviruses. Many CMV genes are involved in evading detection by the host immune response, and others have roles in cell tropism. CMV replicates systemically, and thus, has adapted to various biological niches within the host. Different biological niches may place competing demands on the virus, such that genes that are favorable in some contexts are unfavorable in others. The outcome of infection is dependent on the cell type. In fibroblasts, the virus replicates lytically to produce infectious virus. In other cell types, such as myeloid progenitor cells, there is an initial burst of lytic gene expression, which is subsequently silenced through epigenetic repression, leading to establishment of latency. Latently infected monocytes disseminate the virus to various organs. Latency is established through cell type specific mechanisms of transcriptional silencing. In contrast, reactivation is triggered through pathways activated by inflammation, infection, and injury that are common to many cell types, as well as differentiation of myeloid cells to dendritic cells. Thus, CMV has evolved a complex relationship with the host immune response, in which it exploits cell type specific mechanisms of gene regulation to establish latency and to disseminate infection systemically, and also uses the inflammatory response to infection as an early warning system which allows the virus to escape from situations in which its survival is threatened, either by cellular damage or infection of the host with another pathogen. Spontaneous reactivation induced by cellular aging/damage may explain why extensive expression of lytic genes has been observed in recent studies using highly sensitive transcriptome analyses of cells from latently infected individuals. Recent studies with animal models highlight the potential for harnessing the host immune response to blunt cellular injury induced by organ transplantation, and thus, prevent reactivation of CMV and its sequelae.

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A European Multicenter Study of Chronic Graft-Versus-Host Disease

Cited by 53 publications

References 0 publications

An ethnic role for chronic, but not acute, graft‐versus‐host disease after HLA‐identical sibling stem cell transplantation

An ethnic role for chronic, but not acute, graft‐versus‐host disease after HLA‐identical sibling stem cell transplantation

Risk factors for moderate-to-severe chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Cytomegalovirus Latency and Reactivation: An Intricate Interplay With the Host Immune Response

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