Complete remission of sclerodermatous cutaneous graft‐versus‐host disease after low‐dose interleukine‐2 treatment

2020 ◽  
Vol 34 (12) ◽  
Author(s):  
M. Weiss ◽  
A. Masson ◽  
M. Robin ◽  
R. Peffault de Latour ◽  
M. Bagot ◽  
...  
Keyword(s):  
Complete Remission ◽  
Graft Versus Host Disease ◽  
Low Dose ◽  
Host Disease ◽  
Graft Versus Host

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

scholarly journals Thalidomide as salvage therapy for chronic graft-versus-host disease

Blood ◽  
1995 ◽  
Vol 86 (9) ◽  
pp. 3604-3609 ◽  
Author(s):  
PM Parker ◽  
N Chao ◽  
A Nademanee ◽  
MR O'Donnell ◽  
GM Schmidt ◽  
...  
Keyword(s):  
Side Effects ◽  
Complete Remission ◽  
Graft Versus Host Disease ◽  
Dose Intensity ◽  
Drug Discontinuation ◽  
Effective Agent ◽  
Host Disease ◽  
Graft Versus Host ◽  
Number Of Patients ◽  
High Incidence

Thalidomide has been reported to be an effective agent for treatment of chronic graft-versus-host disease (CGVHD). To determine the efficacy of this agent in patients with refractory CGVHD a total of 80 patients who failed to respond to prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide. Sixteen patients (20%) had a sustained response, 9 with a complete remission and 7 with a partial response. Twenty-nine patients (36%) had thalidomide discontinued because of side effects, which included sedation, constipation, neuritis, skin rash, and neutropenia. Side effects were reversible with drug discontinuation except for mild residual neuritis in one case. Rashes and neutropenia have not previously been reported as thalidomide side effects when used for CGVHD treatment. We conclude thalidomide is immunosuppressive and active in the treatment of CGVHD. A high incidence of reversible side effects limited dose intensity and reduced the number of patients who could benefit from treatment.

scholarly journals Functional analysis of clinical response to low-dose IL-2 in patients with refractory chronic graft-versus-host disease

2019 ◽  
Vol 3 (7) ◽  
pp. 984-994 ◽  
Author(s):  
Jennifer S. Whangbo ◽  
Haesook T. Kim ◽  
Sarah Nikiforow ◽  
John Koreth ◽  
Ana C. Alho ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Low Dose ◽  
B Cell Lymphoma ◽  
Host Disease ◽  
Graft Versus Host ◽  
Response Groups

Abstract Patients with chronic graft-versus-host disease (cGVHD) have a paucity of regulatory CD4 T cells (CD4Tregs) that mediate peripheral tolerance. In clinical trials, daily low-dose interleukin-2 (IL-2) has been administered safely for prolonged periods in patients with steroid-refractory cGVHD. Peripheral CD4Tregs expand dramatically in all patients during IL-2 therapy but clinical improvement was observed in ∼50% of patients. Here, we examined the impact of low-dose IL-2 therapy on functional T-cell markers and the T-cell repertoire within CD4Tregs, conventional CD4 T cells (CD4Tcons), and CD8+ T cells. IL-2 had profound effects on CD4Tregs homeostasis in both response groups including selective expansion of the naive subset, improved thymic output, and increased expression of Ki67, FOXP3, and B-cell lymphoma 2 within CD4Tregs. Similar changes were not seen in CD4Tcons or CD8 T cells. Functionally, low-dose IL-2 enhanced, in vitro, CD4Treg-suppressive activity in both response groups, and all patient CD4Tcons were similarly suppressed by healthy donor CD4Tregs. High-throughput sequencing of the T-cell receptor β (TCRβ) locus demonstrated that low-dose IL-2 therapy increased TCR repertoire diversity and decreased evenness within CD4Tregs without affecting CD4Tcons or CD8 T cells. Using clone-tracking analysis, we observed rapid turnover of highly prevalent clones in CD4Tregs as well as the conversion of CD4Tcons to CD4Tregs. After 12 weeks of daily IL-2, clinical responders had a greater influx of novel clones within the CD4Treg compartment compared with nonresponders. Further studies to define the function and specificity of these novel CD4Treg clones may help establish the mechanisms whereby low-dose IL-2 therapy promotes immune tolerance.

Syngeneic Hematopoietic Stem Cell Transplantation in Acute Leukaemia. A Report of the Acute Leukaemia Working Party of the EBMT.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2303-2303
Author(s):  
Loic Fouillard ◽  
Myriam Labopin ◽  
Eliane Gluckman ◽  
Alois Gratwohl ◽  
Francesco Frassoni ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Leukaemia ◽  
Adult Patients ◽  
Host Disease ◽  
Graft Versus Host ◽  
Number Of Patients

Abstract Syngeneic haematopoietic stem cell transplantation (HSCT) is a rare situation and is usually characterised by a high relapse rate because of the absence of graft versus leukaemia effect. We report results of syngeneic HSCT reported to the EBMT registry from 1975 to 2003. One hundred and 24 acute myeloid leukaemia (AML) and 104 acute lymphoblastic leukaemia (ALL) were reported comprising 150 adults and 78 children, 133 males and 95 females. The number of patients in first complete remission (CR1) was 137, comprising 93 AML (72 adults and 21 children) and 44 ALL (33 adults and 11 children). The number of patients in second complete remission (CR2) was 52 comprising 12 AML (9 adults and 3 children) and 40 ALL (11 adults and 29 children). The number of patients in more advanced disease (AD) was 39 comprising 19 AML (16 adults and 3 children) and 20 ALL (9 adults and 11 children). Total body irradiation was given to 36% of patients. Prophylaxis of graft versus host disease was given to 10% of patients. Source of stem cells was bone marrow for 81% of patients, peripheral blood for 18% and both for 1%. Outcome at 5 years showed for adult patients with AML in CR1 (n=72) a leukaemia free survival (LFS) of 56+/−7%, a relapse incidence (RI) of 37+/−7% and a non relapse mortality (NMR) of 11+/−5%. For adult patients with ALL in CR1 (n=33), LFS was 60+/−10%, RI 38+/−10% and NRM 3+/−3%. Outcome at 5 years showed for children with AML in CR1 (n=21) a LFS of 61+/−11%, a RI of 39+/−11% and a NMR of 0%. For children with ALL in CR2 (n=29), LFS was 46+/−10%, RI 52+/−10% and NRM 5+/−5%. Acute graft versus host disease (GVHD) was diagnosed in 12% of patients, 7% grade 1 and 5% grade ≥ 2. Chronic GVHD was observed in 2% of patients. These retrospective study indicates that syngeneic HSCT can lead to a high LFS in patients with acute leukaemia in CR1 and that GVHD is not a rare event. A graft versus leukemia effect is highly probable in syngeneic HSCT.

Low-Dose Antithymocyte Globulin for Treatment of Steroid-Pulse-Resistant Acute Graft-versus-Host Disease

2003 ◽  
Vol 77 (1) ◽  
pp. 99-102 ◽  
Author(s):  
Kazuteru Ohashi ◽  
Yuji Tanaka ◽  
Shin-ichiro Mori ◽  
Yoshiki Okuyama ◽  
Kiyoshi Hiruma ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Antithymocyte Globulin ◽  
Low Dose ◽  
Host Disease ◽  
Steroid Pulse ◽  
Graft Versus Host ◽  
Acute Graft

Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1601-1605 ◽  
Author(s):  
Joseph H. Antin ◽  
Haesook T. Kim ◽  
Corey Cutler ◽  
Vincent T. Ho ◽  
Stephanie J. Lee ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Low Dose ◽  
Acute Gvhd ◽  
Blood Levels ◽  
High Risk Population ◽  
Unrelated Donor ◽  
Actuarial Survival ◽  
Host Disease ◽  
Graft Versus Host ◽  
Dose Methotrexate

AbstractWe studied the feasibility and activity of adding sirolimus to tacrolimus and low-dose methotrexate as graft-versus-host disease (GVHD) prophylaxis in recipients of alternative donor transplants. Forty-one patients with hematologic malignancies were conditioned with cyclophosphamide and total body irradiation. Marrow stem cells were from an HLA-A, -B, and -DR compatible, unrelated donor (n = 26, 68%), froma5of6 antigen-matched unrelated donor (n = 8, 20%), or from a 5 of 6 antigen-matched family member (n = 5, 12%). Therapeutic serum levels of sirolimus were attained in most patients. All evaluable patients engrafted. An absolute neutrophil count of 500/μL was achieved on day +18 (range, 11-32 days). Sustained platelet counts of more than 20 000/ μL were attained on day +29 (range, 14-98 days). Grades 0-I acute GVHD occurred in 75% of patients. Grades II, III, and IV acute GVHD occurred in 13%, 8%, and 5%, respectively (total grades II-IV GVHD, 26%). Median survival is 366 days (95% CI 185, not estimable) and actuarial survival at 1 year is 52%. Oral sirolimus is tolerable, adequate blood levels are achievable, and there is a low rate of acute GVHD compared with historical data in this high-risk population. This novel agent is worthy of further study in allogeneic transplantation.

scholarly journals Ruxolitinib in refractory acute and chronic graft-versus-host disease: a multicenter survey study

2019 ◽  
Vol 55 (3) ◽  
pp. 641-648 ◽  
Author(s):  
Virginia Escamilla Gómez ◽  
◽  
Valentín García-Gutiérrez ◽  
Lucía López Corral ◽  
Irene García Cadenas ◽  
...  
Keyword(s):  
Complete Remission ◽  
Treatment Option ◽  
Graft Versus Host Disease ◽  
Overall Response Rate ◽  
Response Rate ◽  
Line Treatment ◽  
Host Disease ◽  
Safe Treatment ◽  
Graft Versus Host ◽  
Safe Treatment Option

Abstract Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1–5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1–10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23–67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63–89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients.

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