scholarly journals Sustained Immunogenic and Clinical Effects of Low-Dose Interleukin-2 Therapy with an Intermittent Maintenance Method for Refractory Chronic Graft-Versus-Host Disease: Results of Phase1/2a LDIL2-01 Study

2020 ◽  
Vol 26 (3) ◽  
pp. S175
Author(s):  
Yusuke Meguri ◽  
Kazuteru Ohashi ◽  
Yoshihiro Inamoto ◽  
Satoshi Iyama ◽  
Chikako Ohwada ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Low Dose ◽  
Interleukin 2 ◽  
Clinical Effects ◽  
Host Disease ◽  
Graft Versus Host

scholarly journals Dose-escalated interleukin-2 therapy for refractory chronic graft-versus-host disease in adults and children

2019 ◽  
Vol 3 (17) ◽  
pp. 2550-2561 ◽  
Author(s):  
Jennifer S. Whangbo ◽  
Haesook T. Kim ◽  
Nikola Mirkovic ◽  
Lauren Leonard ◽  
Samuel Poryanda ◽  
...  
Keyword(s):  
T Cells ◽  
Graft Versus Host Disease ◽  
Dose Escalation ◽  
Low Dose ◽  
Pediatric Patients ◽  
Phase 1 ◽  
Interleukin 2 ◽  
Host Disease ◽  
Graft Versus Host ◽  
Patient Reported

Abstract Low-dose interleukin-2 (IL-2) therapy for chronic graft-versus-host disease (cGVHD) generates a rapid rise in plasma IL-2 levels and CD4+CD25+CD127−Foxp3+ regulatory T-cell (CD4Treg) proliferation, but both decrease over time despite continued daily administration. To test whether IL-2 dose escalation at the time of anticipated falls in plasma levels could circumvent tachyphylaxis and enhance CD4Treg expansion, we conducted a phase 1 trial in 10 adult and 11 pediatric patients with steroid-refractory cGVHD (www.clinicaltrials.gov: NCT02318082). Daily IL-2 was initiated in children and adults (0.33 × 106 and 0.67 × 106 IU/m2 per day, respectively). Dose escalations were scheduled at weeks 2 and 4 to a maximum dose of 1 × 106 IU/m2 per day in children and 2 × 106 IU/m2 per day in adults. Patients continued at their maximum tolerated dose (MTD) until week 8. Children tolerated IL-2 dose escalation with partial responses (PRs) in 9 of 11 patients (82%) at multiple cGVHD sites, including lung. Patient-reported outcome scores for skin and lung improved significantly in pediatric patients. In contrast, 5 of 10 adults required dose reduction, and only 2 of 7 evaluable patients (29%) had PRs at week 8. CD4Tregs and natural killer cells expanded in both cohorts without significant changes in conventional CD4+ T cells (Tcons) or CD8+ T cells. Children achieved a higher median CD4Treg/Tcon ratio at week 8 (0.4 vs 0.18, P = .02) despite lower IL-2 doses. We show for the first time that low-dose IL-2 is safe and effective in children with advanced cGVHD. In adults, escalation above the previously defined MTD did not improve CD4Treg expansion or clinical response.

CD4+CD25+ Lymphocyte Subsets in Chronic Graft versus Host Disease Patients Undergoing Extracorporeal Photochemotherapy

2007 ◽  
Vol 20 (4) ◽  
pp. 801-807 ◽  
Author(s):  
P. Rubegni ◽  
P. Sbano ◽  
G. Cevenini ◽  
M.G. Perari ◽  
G. Marotta ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
T Regulatory Cells ◽  
Interleukin 2 ◽  
Clinical Effects ◽  
Protective Effects ◽  
Host Disease ◽  
Extracorporeal Photochemotherapy ◽  
Graft Versus Host

Extracorporeal photochemotherapy (ECP) has been used successfully for the treatment of chronic Graft versus Host Disease (cGvHD). However, the mechanism by which ECP exerts its protective effects remains elusive. Some recent observations have suggested a possible role of certain subsets of T lymphocytes with immunosuppressive properties (T-regulatory cells) that coexpress CD4 and high levels of the interleukin-2 receptor chain: CD4+CD25+ T lymphocytes. We studied whether ECP affects the percentage of these cells in the peripheral blood of patients with cGvHD. The study population consisted of 14 patients with cGvHD refractory to systemic steroids. On enrolment in each cycle of ECP, patients underwent clinical examination, blood chemistry analysis and other instrumental procedures to document and assess involvement of the various organs and systems. For cytofluorimetric identification and phenotyping of CD4+CD25+ T lymphocytes, peripheral blood samples were collected in EDTA anticoagulant before ECP, after 48 hours, and after 6 and 12 months from the start of treatment. The 14 patients in this study received a total of more than 300 cycles of ECP, with only minor side effects. The clinical outcome was negative in 2 patients and positive in 12 patients. Within-subject analysis indicated that the percentage of CD4+CD25+ T lymphocytes before ECP and after 12 months of treatment was significantly increased. Our study confirms that changes in the percentage of CD4+CD25+ T cells induced by ECP could be a central aspect in the cascade of immune events leading to the immunological and clinical effects of this treatment in patients with cGvHD.

scholarly journals Low-Dose Interleukin-2 Therapy Restores Regulatory T Cell Homeostasis in Patients with Chronic Graft-Versus-Host Disease

2013 ◽  
Vol 5 (179) ◽  
pp. 179ra43-179ra43 ◽  
Author(s):  
K.-i. Matsuoka ◽  
J. Koreth ◽  
H. T. Kim ◽  
G. Bascug ◽  
S. McDonough ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Regulatory T Cell ◽  
Low Dose ◽  
Interleukin 2 ◽  
T Cell Homeostasis ◽  
Cell Homeostasis ◽  
Host Disease ◽  
Graft Versus Host

Selective T-cell subset ablation demonstrates a role for T1 and T2 cells in ongoing acute graft-versus-host disease: a model system for the reversal of disease

Blood ◽  
2001 ◽  
Vol 98 (12) ◽  
pp. 3367-3375 ◽  
Author(s):  
Jinli Liu ◽  
Britt E. Anderson ◽  
Marie E. Robert ◽  
Jennifer M. McNiff ◽  
Stephen G. Emerson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Late Time ◽  
Clinical Effects ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor T Cells ◽  
T1 And T2

Abstract Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality of allogeneic stem cell transplantation. Strategies to control GVHD while maintaining graft versus leukemia (GVL) include herpes simplex virus thymidine kinase (HSV-tk) gene transduction of donor T cells followed by treatment with ganciclovir (GCV). Alternatively, GVHD and GVL may be mediated by distinct processes. In this regard, whether cytokine polarization occurs and to what degrees various subsets of cytokine-producing T cells mediate GVHD or GVL has been an active area of research using cytokine or cytokine antibody infusion or genetically deficient mice. This study takes a different approach that allows simultaneous investigation into both the mechanisms underlying GVHD reactions and the efficacy of HSV-tk suicide gene-based T-cell deletion. A source of donor T cells, splenocytes from mice transgenic for HSV-tk controlled by elements of either the interleukin-2 (IL-2) or IL-4 promoters (IL-2-tk and IL-4-tk, respectively) was used, thus allowing investigation into the roles of T1 and T2 cells in ongoing GVHD reactions. To assess treatment rather than prevention of GVHD, GCV was started at peak disease. Remarkably, treatment at this late time point rescued mice from the clinical effects of GVHD caused by T cells expressing either transgene. Thus, both T1 and T2 cells play an important role in clinical GVHD in a minor histocompatibility antigen-mismatched setting. In addition, because clinical disease was reversible even at its maximum, these observations provide controlled evidence that this strategy of treating ongoing GVHD could be effective clinically.

PREVENTION OF ACUTE GRAFT-VERSUS-HOST DISEASE BY MONOCLONAL ANTIBODY TO INTERLEUKIN-2 RECEPTOR

The Lancet ◽  
1989 ◽  
Vol 333 (8650) ◽  
pp. 1333-1334 ◽  
Author(s):  
Didier Blaise ◽  
Dominique Maraninchi ◽  
Claude Mawas ◽  
AnneMarie Stoppa ◽  
Michel Hirn ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Host Disease ◽  
Graft Versus Host ◽  
Interleukin 2 Receptor ◽  
Acute Graft

Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 1224-1226 ◽  
Author(s):  
Vincent T. Ho ◽  
David Zahrieh ◽  
Ephraim Hochberg ◽  
Eileen Micale ◽  
Jesse Levin ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Phase 1 ◽  
Interleukin 2 ◽  
Maximum Tolerated Dose ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Denileukin Diftitox ◽  
Steroid Refractory ◽  
Acute Graft

Abstract Denileukin diftitox (Ontak), a recombinant protein composed of human interleukin 2 (IL-2) fused to diphtheria toxin, has selective cytotoxicity against activated lymphocytes expressing the high-affinity IL-2 receptor. We conducted a phase 1 study of denileukin diftitox in 30 patients with steroid refractory acute graft-versus-host disease (GVHD). Seven patients received 9 μg/kg intravenously on days 1 and 15; 18 received 9 μg/kg intravenously on days 1, 3, 5, 15, 17, and 19; and 5 received 9 μg/kg intravenously on days 1 to 5 and 15 to 19. Hepatic transaminase elevation was the dose-limiting toxicity (DLT), and dose level 2 was the maximum tolerated dose (MTD). Overall, 71% of patients responded with complete resolution (12 of 24; 50%) or partial resolution (5 of 24; 21%) of GVHD. Eight of 24 patients (33%) are alive at 6.3 to 24.6 months (median, 7.2 months). Denileukin diftitox is tolerable and has promising activity in steroid-refractory acute GVHD. (Blood. 2004;104:1224-1226)

scholarly journals Reduced Efficacy of Low-dose Topical Steroids in Dry Eye Disease Associated With Graft-versus-Host Disease

2018 ◽  
Vol 190 ◽  
pp. 17-23 ◽  
Author(s):  
Jia Yin ◽  
Ahmad Kheirkhah ◽  
Thomas Dohlman ◽  
Ujwala Saboo ◽  
Reza Dana
Keyword(s):  
Dry Eye ◽  
Graft Versus Host Disease ◽  
Low Dose ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Topical Steroids ◽  
Host Disease ◽  
Graft Versus Host

Efficacy of the interleukin-2 receptor antagonist basiliximab in steroid-refractory acute graft-versus-host disease

2005 ◽  
Vol 130 (4) ◽  
pp. 568-574 ◽  
Author(s):  
Martin Schmidt-Hieber ◽  
Thomas Fietz ◽  
Wolfgang Knauf ◽  
Lutz Uharek ◽  
Werner Hopfenmuller ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Host Disease ◽  
Graft Versus Host ◽  
Interleukin 2 Receptor ◽  
Steroid Refractory ◽  
Acute Graft
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