Triple post transplant cyclophosphamide (PTCY) based GVHD prophylaxis: HLA matched versus HLA haploidentical transplants

Galli, Eugenio; Metafuni, Elisabetta; Giammarco, Sabrina; Limongiello, Maria Assunta; Innocenti, Idanna; Autore, Francesco; Laurenti, Luca; Sorà, Federica; Chiusolo, Patrizia; Teofili, Luciana; Bacigalupo, Andrea; Sica, Simona

doi:10.1038/s41409-022-01574-0

Cited by 9 publications

(10 citation statements)

References 18 publications

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“…Any analysis assessing the donor effect of HF, MS, and UD in allogeneic HCT needs to take into account the HCT methodology being used. For example, when PTCY administration is used for GVHD prophylaxis, a higher frequency of acute GVHD in HF-HCT versus matched UD-or MS-HCT was observed 26,36 which is consistent with our current findings. However, in HCT using PTCY administration, episodes of high, spiking fever were observed early (one to five days) after the graft infusion, which is apparently dependent on the donor-patient HLA disparity and occurred more frequently in HF-HCT.…”

Section: Discussionsupporting

confidence: 92%

A uniform conditioning regimen of busulfan, fludarabine, and antithymocyte globulin for allogeneic haematopoietic cell transplantation from haploidentical family, matched sibling, or unrelated donors—A single‐centre, prospective, explorative study

Choi

Park

et al. 2022

Br J Haematol

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Summary In a prospective, explorative study, the donor‐source difference of haploidentical family (HF), matched sibling (MS), and unrelated donors (UD) was evaluated for the outcome of haematopoietic cell transplantations (HCT) in 101 patients with acute myeloid leukaemia (AML) in complete remission (CR). To eliminate compounding effects, a uniform conditioning regimen containing antithymocyte globulin (ATG) was used. After transplantation, there was a significantly higher cumulative incidence of acute graft‐versus‐host disease (GVHD) in HF‐HCT patients (49%, 7%, and 16% for HF‐, MS‐ and UD‐HCT respectively; p < 0.001). A quarter of acute GVHD cases observed in HF‐HCT patients occurred within three days of engraftment and were characterized by diffuse skin rash, fever, weight gain, and hypoalbuminaemia. This peri‐engraftment acute GVHD was not observed in MS‐HCT or UD‐HCT patients. Additionally, a significantly higher proportion of HF‐HCT patients achieved complete donor chimaerism in the peripheral mononuclear cells at one month (88%, 46%, and 69% for HF‐, MS‐ and UD‐HCT respectively; p = 0.001). There was no significant difference in engraftment, chronic GVHD, leukaemia recurrence, non‐relapse mortality, and patient survival. In patients with AML in CR who received HCT using ATG‐containing conditioning, stronger donor–patient alloreactivity was observed in HF‐HCT, in terms of increased acute GVHD and higher likelihood of complete donor chimaerism.

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Section: Discussionsupporting

confidence: 92%

A uniform conditioning regimen of busulfan, fludarabine, and antithymocyte globulin for allogeneic haematopoietic cell transplantation from haploidentical family, matched sibling, or unrelated donors—A single‐centre, prospective, explorative study

Choi

Park

et al. 2022

Br J Haematol

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“…Indeed PTCY, combined with a CNI and mycophenolate mofetil (MMF) is the other widely used option, originally designed for haploidentical transplants and more recently also for HLA-matched grafts. 39,40 In patients with myelofibrosis, a PTCY-based prophylaxis has been reported with haploidentical grafts, and more recently also for HLA-matched grafts: in the latter case GvHD is expected to be controlled better, although perhaps at the expense of a reduced graft versus leukemia (GvL), resulting in comparable overall survival of the haploidentical and HLA-matched grafts. 35,36,39 A reduced dose of PTCY may also be used, as suggested by a recent report, with very encouraging early results, and a NRM of 7%.…”

Section: Gvhd Prophylaxismentioning

confidence: 99%

“…39,40 In patients with myelofibrosis, a PTCY-based prophylaxis has been reported with haploidentical grafts, and more recently also for HLA-matched grafts: in the latter case GvHD is expected to be controlled better, although perhaps at the expense of a reduced graft versus leukemia (GvL), resulting in comparable overall survival of the haploidentical and HLA-matched grafts. 35,36,39 A reduced dose of PTCY may also be used, as suggested by a recent report, with very encouraging early results, and a NRM of 7%. 41 Ex vivo T-cell depletion is an alternative way of preventing GvHD: the Memorial Sloan Kettering has reported very interesting outcome using CD34 selection as a stem cell source, following a busulfan, melphalan fludarabine conditioning, and ATG to prevent rejection: there was no graft failure in 27 patients, with a low rate of acute and chronic GvHD and a 3 year survival of 88%.…”

Section: Gvhd Prophylaxismentioning

confidence: 99%

“…Given the inflammatory nature of myelofibrosis, we anticipate other GvHD prophylactic regimens to be developed in the coming years for this disease. Indeed PTCY, combined with a CNI and mycophenolate mofetil (MMF) is the other widely used option, originally designed for haploidentical transplants and more recently also for HLA‐matched grafts 39,40 . In patients with myelofibrosis, a PTCY‐based prophylaxis has been reported with haploidentical grafts, and more recently also for HLA‐matched grafts: in the latter case GvHD is expected to be controlled better, although perhaps at the expense of a reduced graft versus leukemia (GvL), resulting in comparable overall survival of the haploidentical and HLA‐matched grafts 35,36,39 .…”

Section: Introductionmentioning

confidence: 99%

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2024 update on allogeneic hematopoietic stem cell transplant for myelofibrosis: A review of current data and applications on risk stratification and management

Ali,

Bacigalupo

2024

American J Hematol

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BackgroundAllogeneic hemopoietic stem cell transplantation (HSCT) currently remains the only curative treatment for patients with myelofibrosis (MF). Transplant related mortality (TRM) and relapse, remain two significant complications which need to be addressed.AimsThe aim of this manuscript is to review current available reports on changes which have recently occurred, to improve the outcome of MF patients undergoing an allogeneic HSCT.MethodsPublished papers were used to analyze different aspects of allogeneic HSCT.ResultsChanges and updates are provided on selection of patients, prognostic systems, managing splenomegaly, conditioning regimens, predicting transplant outcome, stem cell sources, stem cell donors, graft versus host disease (GvHD) prophylaxis, patients with blast phase, hematopoietic reconstitution, disease markers, donor chimerism, and treatment of relapse.ConclusionsThe review outlines new transplant platforms which are now available for patients with myelofibrosis, together with persisting problems, among which, older age combined with marrow fibrosis and an inflammatory disease. Relapse also requires aggressive monitoring of drivers mutations, and early cellular therapy.

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“…For other diseases, GvHD prophylaxis consisted of PTCy (50 mg/kg) on days + 3 and + 4, cyclosporine (3 mg/kg) starting on day + 5, and mycophenolate mofetil (15 mg/kg bid) from day + 5 until day + 28 for transplants from MATCHED related donors and until day + 35 for transplants from other donor types. 7 Granulocyte colony-stimulating factor (G-CSF) was used from day + 6 until neutrophil recovery in patients with HAPLO grafts. 8 Infection prophylaxis was based on institutional protocols.…”

Section: Patientsmentioning

confidence: 99%

Effect of HLA Mismatch on Post-Transplant Infections in Allogeneic Hematopoietic Stem Cell Transplantation with PTCy-Based GvHD Prophylaxis

Marra

Galli

Giammarco

et al. 2023

Preprint

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The aim of the study was to assess the risk of infections in the first 100 days in patients grafted from haploidentical donors (HAPLO) (n=116) or HLA-matched donors (MATCHED) (Related, n=29; unrelated n=39): all patients received graft-versus-host disease (GvHD) prophylaxis with post-transplant cyclophosphamide (PTCy), mycophenolate, and cyclosporine. The two groups had comparable age, intensity of conditioning, and disease status; the stem cell source was bone marrow for HAPLO and peripheral blood for MATCHED transplants. HAPLO patients had an increased risk of bloodstream infections (BSI) (HR 2.54; 95% CI 1.39-4.62; p=0.002), in particular gram-positive BSI (HR 4.42; 95% CI 1.57-12.5; p=0.005). HAPLO patients also had increased CMV infection/reactivation (HR 3.51; 95% CI 1.79-6.87; p<0.001) and a trend for increased invasive fungal infections (HR 1.80; 95% CI 0.90-3.57; p=0.10) and EBV infection/reactivation (HR 2.07; 95% CI 0.44-9.70; p=0.35). Overall, post-transplant infections were more likely to result in infection-related mortality in HAPLO grafts (p=0.03). In this single-center study, patients with HAPLO grafts had an increased risk of BSI and CMV infection/reactivation and a trend for increased IFI and EBV infection/reactivation, compared with MATCHED grafts. These findings call for diligent monitoring of infections in patients undergoing a HAPLO transplant.

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Triple post transplant cyclophosphamide (PTCY) based GVHD prophylaxis: HLA matched versus HLA haploidentical transplants

Cited by 9 publications

References 18 publications

A uniform conditioning regimen of busulfan, fludarabine, and antithymocyte globulin for allogeneic haematopoietic cell transplantation from haploidentical family, matched sibling, or unrelated donors—A single‐centre, prospective, explorative study

A uniform conditioning regimen of busulfan, fludarabine, and antithymocyte globulin for allogeneic haematopoietic cell transplantation from haploidentical family, matched sibling, or unrelated donors—A single‐centre, prospective, explorative study

2024 update on allogeneic hematopoietic stem cell transplant for myelofibrosis: A review of current data and applications on risk stratification and management

Effect of HLA Mismatch on Post-Transplant Infections in Allogeneic Hematopoietic Stem Cell Transplantation with PTCy-Based GvHD Prophylaxis

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