Post-Transplant Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil As the New Standard for Graft-Versus-Host Disease (GVHD) Prophylaxis in Reduced Intensity Conditioning: Results from Phase III BMT CTN 1703

Holtan, Shernan G.; Hamadani, Mehdi; Wu, Juan; Malki, Monzr M. Al; Runaas, Lyndsey; Elmariah, Hany; Rezvani, Andrew R.; Gooptu, Mahasweta; Larkin, Karilyn; Shaffer, Brian C.; Jurdi, Najla H El; Loren, Alison W.; Solh, Melhem; Hall, Aric C.; Alousi, Amin M.; Jamy, Omer; Perales, Miguel-Ángel; Yao, Janny M.; Applegate, Kristy; Bhatt, Ami S.; Kean, Leslie S.; Efebera, Yvonne A.; Kitko, Carrie L.; Reshef, Ran; Clark, William; DiFronzo, Nancy L.; Henderson, Lori A.; Jones, Richard J.; Liefer, Eric; Märtens, Michael; Horowitz, Mary M.; Bolaños-Meade, Javier

doi:10.1182/blood-2022-171463

Cited by 39 publications

(31 citation statements)

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“…Another issue is the heterogeneous nature of the treatment however there are also limations to larger studies such as HOVON-96, BMT CTN 1203 and BMT CTN 1703 which had few if any patients treated with myeloablative(MA) regimens and at least one study has associated the use of MA regimens with an increased risk of GVHD. 5,6,7 Also none of these studies looked at the possible contributions of graft content to outcome. Also there are potentially advantages to further reductions of GVHD even in transplanst from matched unelated donors.…”

Section: Discussionmentioning

confidence: 99%

“…5 Similar results have been reported in BMT CTN 1203 and 1703 but those studies and HOVON-96 were almost exclusively composed of patient receiving reduced intensity transplants that might result in less GVHD than myeloablative transplants. 5,6,7 This current study was designed to evaluate the use of PtCy in addition to tacrolimus and MMF in patients receiving mobilized stem cells procured from the peripheral blood of unrelated donors in a myeloablative and a reduced intensity setting. This study aimed to look at what impact speci c cell populations in the graft may have on transplant outcome.…”

Section: Introductionmentioning

confidence: 99%

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Post-transplant cyclophosphamide for unrelated donor peripheral blood stem cell transplant with special attention to graft content and the impact of a higher γδ T cell dose

Wagner

Jeurkar

Leiby

et al. 2023

Preprint

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In this study, PtCy was used in 44 patients along with mycophenolate and tacrolimus with HLA matched (29) and mismatched (15) unrelated. The study was done to determine the impact of graft content on outcome thus all patients had flow cytometric analysis of their graft content including the number of B cells, NK cells, and various T cell subsets. Of the 15 patients with HLA mismatched donors, 12 were one antigen mismatched and 3 were 2 antigen mismatched. Sixteen (36.3%) of the patients developed acute GVHD (without any grade IV acute GVHD). For all patients the median time to ANC engraftment was 18 days while median time to platelet engraftment was 24 days. Mean estimated overall survival was 59.9 months, median overall survival was not reached. Higher γδ T cell dose was associated with the development of acute GVHD (p=0.0038). The use of PtCy in addition to MMF and tacrolimus has been shown to be a reasonable strategy to successfully engraft with unrelated donors. This method, potentially with the added intervention of selective gamma-delta T cell depletion, could increase transplant feasibility in recipient-donor combinations with greater HLA disparity and ensure that ethnic minorities have greater access to stem cell transplants.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Post-transplant cyclophosphamide for unrelated donor peripheral blood stem cell transplant with special attention to graft content and the impact of a higher γδ T cell dose

Wagner

Jeurkar

Leiby

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In a randomized trial including 10 patients with CLL, the addition of PTCy to CNI plus MMF prophylaxis resulted in significant reductions in acute and chronic GVHD following MRD or MUD NMA HCT, without significantly impacting the risk of relapse or NRM (116). Similarly, the preliminary results from another randomized trial showed that the addition of PTCy to tacrolimus and MMF prophylaxis was associated with lower risks of acute and chronic GVHD in the setting of RIC HCT (117,118). In light of these promising findings, further research is needed in larger cohorts of patients with CLL to confirm if ATG, PTCy, a combination of ATG and PTCy, or other emerging GVHD prophylaxis agents such as abatacept may improve the outcomes of allogeneic HCT for CLL by providing protection against GVHD while still preserving the GVL effect (119).…”

Section: Gvhd Prophylaxis Strategiesmentioning

confidence: 97%

The role of allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: A review

2023

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Although the use of allogeneic hematopoietic cell transplantation (HCT) for chronic lymphocytic leukemia (CLL) has declined with the development of novel targeted agents, it continues to play an important role for eligible patients with high-risk or heavily pretreated CLL who lack other treatment options. CLL is susceptible to a potent graft-versus-leukemia (GVL) effect which produces long-lasting remissions in 30-50% of transplanted patients. While allogeneic HCT is associated with significant risks of graft-versus-host disease (GVHD), infection, and non-relapse mortality (NRM), improvements in patient and donor selection, reduced intensity conditioning (RIC), GVHD prophylaxis, and supportive care have rendered this an increasingly safe and effective procedure in the current era. In this review, we discuss recent advances in allogeneic HCT for CLL, with a focus on the optimal evidence-based strategies to maximize benefit and minimize toxicity of this potentially curative cellular therapy.

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“…These data establish posttransplant cyclophosphamide as standard of care for GVHD prophylaxis not only in HD but also in matched-related and unrelated donors using RIC regimens. 89 Matched unrelated donors younger than 35 years are preferred over matched related donors older than 50 years as they are associated with higher disease-free survival and lower relapse. 90 Younger age should be incorporated in the donor selection on a case-by-case basis.…”

Section: Allogeneic Stem Cell Transplantation Optimization: Donor Sel...mentioning

confidence: 99%

Hematopoietic Stem Cell Transplantation for Myelodysplastic Syndromes

2023

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Myelodysplastic syndromes (MDSs) are characterized by a clonal proliferation of hematopoietic stem cells with potential life-threatening cytopenia(s) and transformation to acute myeloid leukemia. Individualized risk stratification is evolving with new molecular models, such as the Molecular International Prognostic Scoring System, for better estimation of leukemic transformation and overall survival. The only potential cure for MDSs is allogeneic transplant, although it is underutilized in MDSs because of advanced patient age and multiple comorbidities. Optimization of transplant relies on improved identification of high-risk patients pretransplant, using targeted therapies leading to deeper molecular response, developing lower toxicity conditioning regimens, engineering better molecular tools for early detection and relapse monitoring, and adding maintenance treatment strategies for high-risk patients posttransplant. This review provides an overview of transplant in MDSs with updates, future directions, and role for novel therapies.

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Post-Transplant Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil As the New Standard for Graft-Versus-Host Disease (GVHD) Prophylaxis in Reduced Intensity Conditioning: Results from Phase III BMT CTN 1703

Cited by 39 publications

References 0 publications

Post-transplant cyclophosphamide for unrelated donor peripheral blood stem cell transplant with special attention to graft content and the impact of a higher γδ T cell dose

Post-transplant cyclophosphamide for unrelated donor peripheral blood stem cell transplant with special attention to graft content and the impact of a higher γδ T cell dose

The role of allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: A review

Hematopoietic Stem Cell Transplantation for Myelodysplastic Syndromes

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