Kinetics of Th1/Th2 cytokines and lymphocyte subsets to predict chronic GVHD after allo-SCT: results of a prospective study

Skert, Cristina; Damiani, D. Doḿınguez; Michelutti, Angela; Patriarca, Francesca; Arpinati, Mario; Filì, Carla; Lucchi, P; Malagola, Michele; Bergonzi, Cesare; Roccaro, Aldo M.; Peli, Annalisa; Ricotta, Doris; Caimi, Luigi; Fanin, Renato; Baccarani, Michele; Russo, Domenico

doi:10.1038/bmt.2009.80

Cited by 45 publications

(36 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…High levels of TNF-a, IL-6, TGF-b and IL-1b and low levels of INF-g and IL-10 are reported in persons with cGVHD. [27][28][29][30][31] A recent study by Imanguli et al 31 challenges this paradigm of cGVHD as type-II cytokine-mediated disorder. Data from this study suggest that activation of the type-I IFN axis is important in oral cGVHD.…”

Section: Pathophysiologymentioning

confidence: 99%

Chronic GVHD: Where are we? Where do we want to be? Will immunomodulatory drugs help?

Linhares

Pavletić

Gale

2012

Bone Marrow Transplant

View full text Add to dashboard Cite

Chronic GVHD (cGVHD) is an important problem after allotransplants. Some risk factors for cGVHD are similar to those of acute GVHD (aGVHD) but others are distinct indicating sometimes overlapping but unique pathogeneses. Precise incidence and prevalence data of cGVHD are lacking because of diverse diagnostic criteria but a 50% risk is a reasonable estimate. Incidence and prevalence of cGVHD are probably growing because of increased use of unrelated donors, blood rather than bone marrow (BM) grafts, decreased early transplant-related mortality (TRM) and increasing frequency of allotransplants. Pathophysiology of cGVHD is complex and poorly understood. Notably, no reliable surrogate end point to predict mechanism(s) of cGVHD has been identified. Therapy of cGVHD is unsatisfactory. Corticosteroids are effective but other drugs are controversial and few are rigorously tested in randomized trials. Highly variable response rates are reported because of small sample sizes and inconsistencies in eligibility, diagnostic and response criteria. We focus on the possible role of immunomodulatory drugs (IMiDs), thalidomide lenalidomide and pomalidomide, in preventing and treating cGVHD. The data suggest activity of thalidomide but at doses not clinically practical in many instances. There are few data with lenalidomide. Trials of pomalidomide, which has immune activities like thalidomide but with fewer adverse effects, are beginning. Because cGVHD is not recently reviewed in Bone Marrow Transplantation, we give a brief background and discuss challenges in diagnosing, understanding and treating cGVHD including the recently proposed National Institutes of Health consensus criteria for cGVHD. 1-3 It occurs in about 50% of persons surviving 41 year post transplant and causes substantial morbidity and mortality. There has been little progress over the past 30 years in preventing and/or treating cGVHD. Moreover, incidence and prevalence are increasing because of several factors including: (1) increased use of blood cell rather than BM grafts; (2) increasing use of incompletely HLA-matched related and unrelated donors; (3) increased use of donor-lymphocyte infusions, especially in the context of reduced-intensity allotransplants; (4) increased number of transplants done each year; and (5) increased proportion of transplants in older persons. [4][5][6] The focus of our review is on the use and potential of IMiD-class drugs to prevent and/or treat cGVHD. These drugs have unique, complex immune regulatory activities. As a prelude, we review some relevant definitional, laboratory and clinical features of cGVHD.

show abstract

Section: Pathophysiologymentioning

confidence: 99%

Chronic GVHD: Where are we? Where do we want to be? Will immunomodulatory drugs help?

Linhares

Pavletić

Gale

2012

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…5 Much effort has been devoted to the understanding of the role of T helper (Th) cell polarization in the manifestation of post transplant complications. Although Th1/Th2 kinetics and lymphocyte subsets are known to influence transplantation outcome, 6 T cells other than Th1 or Th2 are also likely to have a role in mediating post transplant events. Th17 cells belong to a newly identified T cell lineage in addition to the classic Th1 and Th2 subsets.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of genetic variants in the IL-23/Th17 pathway for the outcome of T cell-depleted allogeneic stem cell transplantation

Carvalho

Cunha

Ianni

et al. 2010

Bone Marrow Transplant

View full text Add to dashboard Cite

T helper (Th) 17 cells have emerged as important mediators in infectious and inflammatory diseases and, recently, in transplant rejection. We analyzed the associations between five common genetic variants in the IL-23/ Th17 signaling pathway, namely in IL17A, IL17F and IL23R genes, and clinical outcome in T cell-depleted allogeneic SCT (allo-SCT). In the multivariate analysis, variants in IL23R and IL17A genes were the most important prognostic factors. Thus, patient GA genotype at rs11209026 in IL23R was associated with improved overall survival (hazard ratio (HR) ¼ 0.48; P ¼ 0.028) and, in donor, with decreased risk of fungal infections (P ¼ 0.05). In contrast, patient TC and CC genotypes at rs8193036 in IL17A gene were associated with increased risk of CMV infection (HR ¼ 3.68; P ¼ 0.011) and patient acute GVHD (HR ¼ 7.08; P ¼ 0.008), respectively. These results suggest that genetic variants in the IL-23/Th17 inflammatory pathway are important prognostic factors for the clinical outcome of allo-SCT. Although validation studies are ultimately required, our results would suggest the potential usefulness of IL-23/Th17 genotyping in donor selection and patient evaluation.

show abstract

“…Recent biomarker studies in patients with cGVHD additionally support a hypothesis that Th1 and Th2 cytokine production may play a role in the pathogenesis of the disorder [65]. Increased levels of Th1 cytokines, including IFN-γ, TNF-α, IL-1, and IL-6 have been noted in skin and renal biopsies and in peripheral blood lymphocytes collected from patients with cGVHD [65–67].…”

Section: Discussionmentioning

confidence: 99%

Soluble Tumor Necrosis Factor Receptor: Enbrel (Etanercept) for Subacute Pulmonary Dysfunction Following Allogeneic Stem Cell Transplantation

Yanik

Mineishi

Levine

et al. 2012

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Subacute lung disease, manifested as either obstructive (OLD) or restrictive (RLD) lung dysfunction, is a common complication following allogeneic stem cell transplantation. In each case, therapeutic options are limited, morbidity remains high, and long-term survival is poor. Between 2001 and 2008, 34 patients with noninfectious, obstructive (25) or RLD restrictive lung dysfunction (nine) received etanercept (Enbrel®, Amgen Inc.) 0.4 mg/kg/dose, subcutaneously, twice weekly, for 4 (group A) or 12 weeks (group B). Corticosteroids (if present at study entry) were kept constant for the initial 4 weeks of therapy and then tapered as tolerated. Thirty-one of 34 (91%) subjects were evaluable for response, and 10 (32%) met primary response criteria. There was no difference in response based on the duration of treatment (29% group A versus 35% group B; P =.99), the presence of RLD or OLD (33% versus 32%; P =.73), or the severity of pulmonary disease at study onset. Estimated 5-year overall survival rates following therapy were 61% (95% confidence interval, 46%–80%) for all subjects and 90% (95% confidence level, 73% –100%) for the 10 who met the primary response criteria. Five-year survival estimates for subjects treated with RLD was 44%, compared with 67% for those treated for OLD (P =.19). Etanercept was well tolerated, with no bacteremia or viremia observed. Pathogens were noted on posttherapy bronchoalveolar lavage in two cases. These data support the development of expanded clinical trials to study etanercept as a therapeutic agent for subacute lung injury after allogeneic stem cell transplantation.

show abstract

Kinetics of Th1/Th2 cytokines and lymphocyte subsets to predict chronic GVHD after allo-SCT: results of a prospective study

Cited by 45 publications

References 40 publications

Chronic GVHD: Where are we? Where do we want to be? Will immunomodulatory drugs help?

Chronic GVHD: Where are we? Where do we want to be? Will immunomodulatory drugs help?

Prognostic significance of genetic variants in the IL-23/Th17 pathway for the outcome of T cell-depleted allogeneic stem cell transplantation

Soluble Tumor Necrosis Factor Receptor: Enbrel (Etanercept) for Subacute Pulmonary Dysfunction Following Allogeneic Stem Cell Transplantation

Contact Info

Product

Resources

About