Posttransplantation cyclophosphamide and sirolimus for prevention of GVHD after HLA-matched PBSC transplantation

Greco, Raffaella; Lorentino, Francesca; Morelli, Mara; Giglio, Fabio; Mannina, Daniele; Assanelli, Andrea; Mastaglio, Sara; Dalto, Serena; Perini, Tommaso; Lazzari, Lorenzo; Piemontese, Simona; Corti, Consuelo; Marcatti, Magda; Bernardi, Massimo; Stanghellini, Maria Teresa Lupo; Ciceri, Fabio; Peccatori, Jacopo

doi:10.1182/blood-2016-06-723205

Cited by 48 publications

(39 citation statements)

References 24 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Solomon et al, using sirolimus in addition to PTC, reported an incidence of acute GVHD grades II to IV, acute GVHD grades III and IV, and chronic GVHD of 46%, 15%, and 31%, respectively [21]. A similar study with shorter follow-up examining the combination of PTC, sirolimus, and, in patients receiving grafts from unrelated donors, MMF, reported incidences of acute GVHD grades II to IV, acute GVHD grades III and IV, and chronic GVHD of 23%, 4%, and 13%, respectively [22]. Although these results seem favorable, the re-addition of calcineurin and mTOR inhibitors to PTC potentially hinders several benefits of PTC.…”

Section: Discussionmentioning

confidence: 96%

Calcineurin and mTOR Inhibitor–Free Post-Transplantation Cyclophosphamide and Bortezomib Combination for Graft-versus-Host Disease Prevention after Peripheral Blood Allogeneic Hematopoietic Stem Cell Transplantation: A Phase I/II Study

Al-Homsi

Cole

Muilenburg

et al. 2017

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Graft-versus-host disease (GVHD) hampers the utility of allogeneic hematopoietic stem cell transplantation (AHSCT). The purpose of this study was to determine the feasibility, safety, and efficacy of a novel combination of post-transplantation cyclophosphamide (PTC) and bortezomib for the prevention of GVHD. Patients undergoing peripheral blood AHSCT for hematological malignancies after reduced-intensity conditioning with grafts from HLA-matched related or unrelated donors were enrolled in a phase I/II clinical trial. Patients received a fixed dose of PTC and an increasing dose of bortezomib in 3 cohorts, from .7 to 1 and then to 1.3 mg/m, administered 6 hours after graft infusion and 72 hours thereafter, during phase I. The study was then extended at the higher dose in phase II for a total of 28 patients. No graft failure and no unexpected grade ≥3 nonhematologic toxicities were encountered. The median times to neutrophil and platelet engraftment were 16 and 27 days, respectively. Day +100 treatment-related mortality was 3.6% (95% confidence interval [CI], .2% to 15.7%). The cumulative incidences of grades II to IV and grades III and IV acute GVHD were 35.9% (95% CI, 18.6% to 53.6%) and 11.7% (95% CI, 2.8% to 27.5%), respectively. The incidence of chronic GVHD was 27% (95% CI, 11.4% to 45.3%). Progression-free survival, overall survival, and GVHD and relapse-free survival rates were 50% (95% CI, 30.6% to 66.6%), 50.8% (95% CI, 30.1% to 68.2%), and 37.7% (95% CI, 20.1% to 55.3%), respectively. Immune reconstitution, measured by CD3, CD4, and CD8 recovery, was prompt. The combination of PTC and bortezomib for the prevention of GVHD is feasible, safe, and yields promising results. The combination warrants further examination in a multi-institutional trial.

show abstract

Section: Discussionmentioning

confidence: 96%

Calcineurin and mTOR Inhibitor–Free Post-Transplantation Cyclophosphamide and Bortezomib Combination for Graft-versus-Host Disease Prevention after Peripheral Blood Allogeneic Hematopoietic Stem Cell Transplantation: A Phase I/II Study

Al-Homsi

Cole

Muilenburg

et al. 2017

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

show abstract

“…Post-transplant cyclophosphamide (PTCY) has been used both in the setting of sibling donor transplants and haploidentical transplants and has been shown to be associated with a low incidence of acute and chronic GVHD [7][8][9][10]. We undertook a prospective, phase II, single-arm study to evaluate the utility of PTCY as the sole GVHD prophylaxis in patients with SAA undergoing sibling donor HSCT.…”

Section: Introductionmentioning

confidence: 99%

Post-Transplant Cyclophosphamide as Sole Graft-versus-Host Disease Prophylaxis Is Feasible in Patients Undergoing Peripheral Blood Stem Cell Transplantation for Severe Aplastic Anemia Using Matched Sibling Donors

George

Devasia

et al. 2018

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

High-dose cyclophosphamide (PTCY) after allogeneic hematopoietic cell transplantation (HSCT) has been shown to be effective in preventing graft-versus-host disease (GVHD) after HLA-matched bone marrow transplantation. We performed a phase II study of PTCY given at 50 mg/kg i.v. on days 3 and 4 as the sole GVHD prophylaxis after HSCT for severe aplastic anemia (SAA) in patients receiving granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (PBSC) grafts from HLA-matched related donors after conditioning with fludarabine, CY, and single-dose total body irradiation. Thirty patients with a median age of 29 years (range, 16 to 49) were enrolled in this study. Engraftment was seen in 27 patients (90%) at a median of 16 days (range, 12 to 21) post-HSCT. None of the patients developed veno-occlusive disease of the liver or hemorrhagic cystitis. Grades II to IV acute GVHD was seen in 22% of patients with grades III to IV GVHD in 11.1%. The 2-year cumulative incidence of chronic GVHD was 22.7%. Fourteen patients (46.6%) did not require any further immunosuppression after receiving PTCY. Comparing with 2 historical cohorts of 30 patients each who received cyclosporine and methotrexate (MTX; at 15 mg/m [MTX15] and 10 mg/m [MTX10]), the incidence of grades II to IV acute GVHD was lower, albeit not significantly, with the use of PTCY (PTCY, 22.2%, vs MTX15, 37.1%, vs MTX10, 53.8%; P = .056), whereas rates of chronic GVHD were significantly reduced (PTCY, 22.7%, vs MTX15, 63.6%, vs MTX10, 76.2%; P = .013). Viral infections including cytomegalovirus were significantly higher with the use of PTCY (60%) compared with cyclosporine and MTX (MTX15, 23.3%, vs MTX10, 33.3%; P = .008). Overall survival was similar between the 3 groups. We conclude that PTCY as the sole GVHD prophylaxis is associated with low rates of acute and chronic GVHD in patients undergoing PBSC transplant for SAA using HLA-matched donors. This trial is registered at CTRI/2010/091/001480.

show abstract

“…MMF was added to the regimen in patients receiving MUD transplants. The incidence of grades II-IV acute and cGvHD seemed better at 23 and 13% (36).…”

Section: Ptcy and Cni Or Mtor Inhibitors In Mrd And Mud Transplantmentioning

confidence: 90%

Post-transplantation Cyclophosphamide: From HLA-Haploidentical to Matched-Related and Matched-Unrelated Donor Blood and Marrow Transplantation

Williams

Cirrone²,

Cole³

et al. 2020

Front. Immunol.

View full text Add to dashboard Cite

Following allogeneic blood and marrow transplantation (BMT), graft-versus-host disease (GvHD) continues to represent a significant cause of treatment failure, despite the routine use of conventional, mainly calcineurin inhibitor-based prophylaxis. Recently, posttransplant cyclophosphamide (PTCy) has emerged as a safe and efficacious alternative. First, omitting the need for ex vivo T-cell depletion in the setting of haploidentical transplantation, growing evidence supports PTCy role in GvHD prevention in matchedrelated and matched-unrelated transplants. Through improved understanding of GvHD pathophysiology and advancements in drug development, PTCy emerges as a unique opportunity to design calcineurin inhibitor-free strategies by integrating agents that target different stages of GvHD development.

show abstract

Posttransplantation cyclophosphamide and sirolimus for prevention of GVHD after HLA-matched PBSC transplantation

Cited by 48 publications

References 24 publications

Calcineurin and mTOR Inhibitor–Free Post-Transplantation Cyclophosphamide and Bortezomib Combination for Graft-versus-Host Disease Prevention after Peripheral Blood Allogeneic Hematopoietic Stem Cell Transplantation: A Phase I/II Study

Calcineurin and mTOR Inhibitor–Free Post-Transplantation Cyclophosphamide and Bortezomib Combination for Graft-versus-Host Disease Prevention after Peripheral Blood Allogeneic Hematopoietic Stem Cell Transplantation: A Phase I/II Study

Post-Transplant Cyclophosphamide as Sole Graft-versus-Host Disease Prophylaxis Is Feasible in Patients Undergoing Peripheral Blood Stem Cell Transplantation for Severe Aplastic Anemia Using Matched Sibling Donors

Post-transplantation Cyclophosphamide: From HLA-Haploidentical to Matched-Related and Matched-Unrelated Donor Blood and Marrow Transplantation

Contact Info

Product

Resources

About