scholarly journals Post Transplant Cyclophosphamide (PTCy) with Anti-Thymocyte Globulin (ATG) Effectively Reduces the Severe (Grade III-IV) Acute Graft-Versus-Host Disease (GVHD) When Compared to ATG Alone in Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplants

2017 ◽  
Vol 23 (3) ◽  
pp. S365
Author(s):  
Uday Deotare ◽  
David Loach ◽  
Frank Michelis ◽  
Dennis (Dong Hwan) Kim ◽  
Santhosh Thyagu ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Graft Versus Host ◽  
Post Transplant ◽  
Cell Transplants ◽  
Grade Iii ◽  
Severe Grade ◽  
Acute Graft

Impact of Defibrotide in the Prevention of Acute Graft-Versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation

2022 ◽  
pp. 106002802110681
Author(s):  
Rémi Tilmont ◽  
Ibrahim Yakoub-Agha ◽  
Nassima Ramdane ◽  
Micha Srour ◽  
Valérie Coiteux ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Control Group ◽  
Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Background Defibrotide is indicated for patients who develop severe sinusoidal obstructive syndrome following allogeneic hematopoietic cell transplantation (allo-HCT). Preclinical data suggested that defibrotide carries a prophylactic effect against acute graft-versus-host disease (aGVHD). Objective The purpose of this study was to investigate the effect of defibrotide on the incidence and severity of aGVHD. Methods This single-center retrospective study included all consecutive transplanted patients between January 2014 and December 2018. A propensity score based on 10 predefined confounders was used to estimate the effect of defibrotide on aGVHD via inverse probability of treatment weighting (IPTW). Results Of the 482 included patients, 64 received defibrotide (defibrotide group) and 418 did not (control group). Regarding main patient characteristics and transplantation modalities, the two groups were comparable, except for a predominance of men in the defibrotide group. The median age was 55 years (interquartile range [IQR]: 40-62). Patients received allo-HCT from HLA-matched related donor (28.6%), HLA-matched unrelated donor (50.8%), haplo-identical donor (13.4%), or mismatched unrelated donor (7.0%). Stem cell source was either bone marrow (49.6%) or peripheral blood (50.4%). After using IPTW, exposure to defibrotide was not significantly associated with occurrence of aGVHD (HR = 0.97; 95% CI 0.62-1.52; P = .9) or occurrence of severe aGVHD (HR = 1.89, 95% CI: 0.98-3.66; P = .058). Conclusion and Relevance Defibrotide does not seem to have a protective effect on aGVHD in patients undergoing allo-HCT. Based on what has been reported to date and on these results, defibrotide should not be considered for the prevention of aGVHD outside clinical trials.

Naive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease

2022 ◽  
Author(s):  
Marie Bleakley ◽  
Alison Sehgal ◽  
Stuart Seropian ◽  
Melinda A. Biernacki ◽  
Elizabeth F. Krakow ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Cumulative Incidence ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Grade Iii

PURPOSE Graft-versus-host disease (GVHD) causes morbidity and mortality following allogeneic hematopoietic cell transplantation. Naive T cells (TN) cause severe GVHD in murine models. We evaluated chronic GVHD (cGVHD) and other outcomes in three phase II clinical trials of TN-depletion of peripheral blood stem-cell (PBSC) grafts. METHODS One hundred thirty-eight patients with acute leukemia received TN-depleted PBSC from HLA-matched related or unrelated donors following conditioning with high- or intermediate-dose total-body irradiation and chemotherapy. GVHD prophylaxis was with tacrolimus, with or without methotrexate or mycophenolate mofetil. Subjects received CD34-selected PBSC and a defined dose of memory T cells depleted of TN. Median follow-up was 4 years. The primary outcome of the analysis of cumulative data from the three trials was cGVHD. RESULTS cGVHD was very infrequent and mild (3-year cumulative incidence total, 7% [95% CI, 2 to 11]; moderate, 1% [95% CI, 0 to 2]; severe, 0%). Grade III and IV acute GVHD (aGVHD) occurred in 4% (95% CI, 1 to 8) and 0%, respectively. The cumulative incidence of grade II aGVHD, which was mostly stage 1 upper gastrointestinal GVHD, was 71% (95% CI, 64 to 79). Recipients of matched related donor and matched unrelated donor grafts had similar rates of grade III aGVHD (5% [95% CI, 0 to 9] and 4% [95% CI, 0 to 9]) and cGVHD (7% [95% CI, 2 to 13] and 6% [95% CI, 0 to 12]). Overall survival, cGVHD-free, relapse-free survival, relapse, and nonrelapse mortality were, respectively, 77% (95% CI, 71 to 85), 68% (95% CI, 61 to 76), 23% (95% CI, 16 to 30), and 8% (95% CI, 3 to 13) at 3 years. CONCLUSION Depletion of TN from PBSC allografts results in very low incidences of severe acute and any cGVHD, without apparent excess risks of relapse or nonrelapse mortality, distinguishing this novel graft engineering strategy from other hematopoietic cell transplantation approaches.

scholarly journals Tacrolimus and minidose methotrexate for prevention of acute graft- versus-host disease after matched unrelated donor marrow transplantation

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4383-4389 ◽  
Author(s):  
D Przepiorka ◽  
C Ippoliti ◽  
I Khouri ◽  
M Woo ◽  
R Mehra ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Advanced Disease ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Unrelated Donors ◽  
Acute Graft

Abstract Thirty adults with leukemia or lymphoma undergoing marrow transplantation from HLA-compatible unrelated donors received tacrolimus (FK506), a new immunosuppressive macrolide lactone, and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 36 years (range 21 to 49 years). Twenty-four patients had advanced disease, and 11 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/d intravenously (i.v.) by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued through day 180 posttransplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6, and 11. All patients engrafted. Grades 2–4 GVHD occurred in 34% (95% CI, 17% to 52%), and grades 3–4 GVHD in 17% (95% CI, 3% to 31%). Mild renal toxicity was common before day 100; 63% of patients had a doubling of creatinine, and 52% had a peak creatinine greater than 2 mg/dL, but only one patient was dialyzed. The median last i.v. dose of tacrolimus was 53% of the scheduled dose, and the median oral dose on day 100 was 41% of that scheduled. Overall survival at 1 year was 47% (95% CI, 27% to 66%). We conclude that tacrolimus can be combined safely with minidose methotrexate, and the combination has substantial activity in preventing acute GVHD after unrelated donor marrow transplantation.

scholarly journals Tacrolimus and minidose methotrexate for prevention of acute graft- versus-host disease after matched unrelated donor marrow transplantation

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4383-4389 ◽  
Author(s):  
D Przepiorka ◽  
C Ippoliti ◽  
I Khouri ◽  
M Woo ◽  
R Mehra ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Advanced Disease ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Unrelated Donors ◽  
Acute Graft

Thirty adults with leukemia or lymphoma undergoing marrow transplantation from HLA-compatible unrelated donors received tacrolimus (FK506), a new immunosuppressive macrolide lactone, and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 36 years (range 21 to 49 years). Twenty-four patients had advanced disease, and 11 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/d intravenously (i.v.) by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued through day 180 posttransplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6, and 11. All patients engrafted. Grades 2–4 GVHD occurred in 34% (95% CI, 17% to 52%), and grades 3–4 GVHD in 17% (95% CI, 3% to 31%). Mild renal toxicity was common before day 100; 63% of patients had a doubling of creatinine, and 52% had a peak creatinine greater than 2 mg/dL, but only one patient was dialyzed. The median last i.v. dose of tacrolimus was 53% of the scheduled dose, and the median oral dose on day 100 was 41% of that scheduled. Overall survival at 1 year was 47% (95% CI, 27% to 66%). We conclude that tacrolimus can be combined safely with minidose methotrexate, and the combination has substantial activity in preventing acute GVHD after unrelated donor marrow transplantation.

scholarly journals Effective Strategy to Prevent Acute Graft-Versus-Host Disease in Unrelated Donor Allogeneic Hematopoietic Cell Transplants By Using a Combination of Anti-Thymocyte Globulin (ATG), Post-Transplant Cyclophosphamide and Cyclosporine

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5781-5781
Author(s):  
Uday Deotare ◽  
David Loach ◽  
Fotios V. Michelis ◽  
Dennis D. Kim ◽  
Santhosh Thyagu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematological Malignancies ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Graft Versus Host ◽  
Post Transplant ◽  
Stem Cell Source ◽  
Cell Source ◽  
Cell Transplants ◽  
Grade Iii

Abstract Introduction:Acute Graft-versus-Host Disease (aGVHD) is a frequent complication of Allogeneic Hematopoietic cell transplants (allo-HCT); aGVHD, especially Grade III-IV, can be lethal with increased morbidity and mortality and can occur in upto 40-50% of allo-HCT. GVHD prophylaxis has been used for control of GVHD, with use of calcineurin inhibitors, anti-metabolites and anti T cell antibodies. Use of Post-transplant Cyclophosphamide (PTCy) has recently been used extensively in haplo-identical transplant setting with promising results. However, PtCy has mainly been used in patients with BM as the stem cell source. In those patients with PBSC as the stem cell source, alone PTCy has been associated with clinically significant acute and chronic GVHD. As most of our patients use PBSC as the graft source, we hypothesized to combine both ATG and PTCy to reduce incidence of both acute and chronic GVHD in our patient cohort. Here we present a small cohort data using a combination of all these agents to effectively reduce aGVHD in hematological malignancies.. Methods:A total of 28 patients with hematological malignancies, who had an unrelated donor underwent allo-HCT at our center from 1 Oct 2015 to 31 Mar 2016. The characteristics of the patients are summarized in Table 1. The conditioning regimen was either myeloablative (MAC, namely FBT400) or Reduced Intensity (RIC, namely FBT200) in patients with age ≤ 60 and >60 years, respectively. After interim analysis when increased non-hematological toxicity was observed in the MAC arm, all patients subsequently received FBT 200 conditioning. Peripheral blood was used as the stem cell source in all patients. Filgrastim was used from day +7 onwards for 13 patients. Special emphasis was given to incidence of acute GVHD, infections, regimen related toxicities and engraftment. Results:Out of total of 28 patients, aGVHD was seen in only 6 (21.4%) patients, five of which had skin involvement (Grade I-II) and one suspected liver involvement (Grade III), all of which responded rapidly to steroids. However, we did observe increased toxicities such as sinusoidal obstruction syndrome (32%), bacterial infections (68%) and viral infections (46%; CMV reactivations in 64%). Primary disease relapse, secondary graft failure and EBV reactivations were seen in 10% of cases, with documented Post Transplant Lymphoproliferative Disorder (PTLD) in only 2 patients. The overall survival of the entire cohort was 67.8% with a median duration of 6 months (range; 3-8 months). In comparison to MAC, RIC regimen was found to be superior with no Gr III-IV aGVHD, less toxicity and improved survival (RIC-82% vs MAC-45%). Conclusions: Combination of ATG-PTCy-CsA is an effective strategy to reduce aGVHD in unrelated donor transplants, albeit with moderate increase in toxicities. RIC with this combination was associated with less organ damage and superior survival. However, a long term follow up is needed to assess relapse and cGVHD. Disclosures No relevant conflicts of interest to declare.

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