Atypical chronic graft-versus-host disease following interferon therapy for chronic myeloid leukaemia relapsing after allogeneic BMT

Serrano, J; Prieto, Elena; Mazarbeitia, F; Román, A; Llamas, Pilar; Tomás, J F

doi:10.1038/sj.bmt.1702746

Cited by 14 publications

(5 citation statements)

References 17 publications

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“…Considering that the patient remains in molecular remission 6 months after cessation of interferon-␣ during which time chronic GVHD has persisted, chronic GVHD, probably induced by interferon-␣, might have contributed to the durable remission in this patient. Serrano et al recently reported a similar case, in which a patient developed atypical chronic GVHD following interferon-␣ for CML relapsing after allogeneic BMT [12] and in which the authors discussed the possible role of interferon in the pathogenesis of GVHD. The patient developed skin lesions on her face and trunk, dysphagia, and fever with respiratory failure and bilateral patchy airspace consolidation of both lungs.…”

Section: Discussionmentioning

confidence: 94%

Sustained molecular remission in a patient with CML in blastic crisis receiving dose‐reduced hematopoietic stem‐cell transplantation followed by early withdrawal of cyclosporine and prophylactic use of interferon‐α

Hamaki¹,

Kami²,

Momomura³

et al. 2002

American J Hematol

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A 54-year-old man with chronic myelocytic leukemia in blastic phase received reducedintensity transplantation (RIST) from an HLA-identical unrelated donor. The preparative regimen consisted of busulfan, fludarabine, and anti-thymocyte globulin. Graft-versushost disease (GVHD) prophylaxis was cyclosporine alone. Because he had a high risk of relapse, we discontinued cyclosporine on day 37, but he did not develop any signs of acute GVHD. To induce GVHD and augment a graft-versus-leukemia effect, we initiated interferon-␣ therapy on day 80 to a maximum dosage of three million units five times a week. He achieved molecular remission on day 94 followed by the development of extensive chronic GVHD the severity of which paralleled to the dose of interferon-␣ GVHD gradually subsided after discontinuation of interferon-␣ and the patient remains in molecular remission 18 months after transplantation. This case suggests that early withdrawal of cyclosporine and the prophylactic use of interferon-␣ are promising in RIST for high-risk leukemia. Am.

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Section: Discussionmentioning

confidence: 94%

Sustained molecular remission in a patient with CML in blastic crisis receiving dose‐reduced hematopoietic stem‐cell transplantation followed by early withdrawal of cyclosporine and prophylactic use of interferon‐α

Hamaki¹,

Kami²,

Momomura³

et al. 2002

American J Hematol

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“…IFNα treatment exacerbates disease in lupus-prone murine models (54, 55), and produces lupus-like rashes and anti-nuclear antibodies in man (56). Similarly, use of IFNα after transplant to treat patients relapsing with chronic myelogenous leukemia has been reported to produce severe CGVHD (57, 58). The commonalities between CGVHD and systemic autoimmune disorders are particularly relevant to the development of new approaches to CGVHD therapy.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of IFN-Inducible and Damage-Response Pathways in Chronic Graft-versus-Host Disease

Hakim

Memon

Jin

et al. 2016

The Journal of Immunology

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Although Chronic Graft-versus-Host Disease (CGVHD) is the primary non-relapse complication of allogeneic transplantation, understanding of its pathogenesis is limited. To identify the main operant pathways across the spectrum of CGVHD, we analyzed gene expression in circulating monocytes, chosen as in situ systemic reporter cells. Microarrays identified two interrelated pathways: (1) Interferon-inducible genes and (2) innate receptors for cellular damage. Corroborating these with multiplex RNA quantitation, we found that multiple IFN-inducible genes (affecting lymphocyte trafficking, differentiation and antigen presentation) were concurrently upregulated in CGVHD monocytes compared to normal and nonCGVHD controls. IFN-inducible chemokines were elevated in both lichenoid and sclerotic CGHVD plasma and linked to CXCR3+ lymphocyte trafficking. Furthermore, the IFN-inducible genes CXCL10 and TNFSF13B (BAFF) levels were correlated at both the gene and plasma levels, implicating IFN-induction as a factor in elevated BAFF levels in CGVHD. In the second pathway, DAMP/PAMP receptor genes capable of inducing Type I IFN were upregulated. Type I IFN-inducible MxA was expressed in proportion to CGVHD activity in skin, mucosa and glands, and expression of TLR and RIG-1 receptor genes correlated with upregulation of Type I IFN-inducible genes in monocytes. Finally, in serial analyses following transplant, IFN-inducible and damage-response genes were upregulated in monocytes at CGVHD onset and declined upon therapy and resolution in both lichenoid and sclerotic CGVHD patients. This interlocking analysis of IFN-inducible genes, plasma analytes and tissue immunohistochemistry strongly supports a unifying hypothesis of induction of IFN by innate response to cellular damage as a mechanism for initiation and persistence of CGVHD.

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“…The therapeutic role of IFN-a in graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) has been known for decades [70,71], especially in the context of relapsing chronic myeloid leukemia following bone marrow transplantation [72]. However, the mechanisms of action remain obscure, and the application of type I IFN in this setting remains controversial [73,74]. A study by Robb et al [75] suggested that the efficacy of type I IFN in protecting patients from GVHD and GVL can be attributed to the suppression of donor CD4 ?…”

Section: T Cellsmentioning

confidence: 99%

Activation and regulation of interferon-β in immune responses

Sin

Yeong

et al. 2012

Immunol Res

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Interferons (IFNs) were discovered more than half a century ago, and extensive research has since identified multifarious roles for type I IFN in human immune responses. Here, we review the functions of IFN-β in innate and adaptive immunity. We also discuss the activation and influence of IFN-β on myeloid cell types, including monocytes and dendritic cells, as well as address the effects of IFN-β on T cells and B cells. Findings from our own laboratory, which explores the molecular mechanisms of IFN-β activation by LPS and viruses, as well as from other groups investigating the regulation of IFN-β by viral proteins and endogenous factors are described. The effects of post-translational modifications of the interferon regulatory factor (IRF)-3 on IFN-β induction are also highlighted. Many unanswered questions remain concerning the regulation of the type I IFN response in inflammation, especially the role of transcription factors in the modulation of inflammatory gene expression, and these questions will form the basis for exciting avenues of future research.

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Atypical chronic graft-versus-host disease following interferon therapy for chronic myeloid leukaemia relapsing after allogeneic BMT

Cited by 14 publications

References 17 publications

Sustained molecular remission in a patient with CML in blastic crisis receiving dose‐reduced hematopoietic stem‐cell transplantation followed by early withdrawal of cyclosporine and prophylactic use of interferon‐α

Sustained molecular remission in a patient with CML in blastic crisis receiving dose‐reduced hematopoietic stem‐cell transplantation followed by early withdrawal of cyclosporine and prophylactic use of interferon‐α

Upregulation of IFN-Inducible and Damage-Response Pathways in Chronic Graft-versus-Host Disease

Activation and regulation of interferon-β in immune responses

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