Combining post-transplant cyclophosphamide with antithymocyte globulin for graft-versus-host disease prophylaxis in hematological malignancies

Duléry, Rémy; Brissot, Éolia; Mohty, Mohamad

doi:10.1016/j.blre.2023.101080

Cited by 18 publications

(7 citation statements)

References 135 publications

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“…Adding ATG did not decrease the rate of GVHD. This is in contradiction with previous studies reporting a decrease in the rate of cGVHD when ATG was added to PTCy [ 11 ]. However, these studies were based on a limited number of patients, had included various doses of ATG or Cy-PT, and reported various grades of cGVHD.…”

Section: Discussioncontrasting

confidence: 99%

Bone marrow graft versus peripheral blood graft in haploidentical hematopoietic stem cells transplantation: a retrospective analysis in1344 patients of SFGM-TC registry

Lacan,

Lambert,

Forcade

et al. 2024

J Hematol Oncol

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The use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remains controversial. Moreover, the value of adding anti-thymoglobulin (ATG) to PTCy is unknown. A total of 1344 adult patients received an unmanipulated haploidentical transplant at 37 centers from 2012 to 2019 for hematologic malignancy. We compared the outcomes of patients according to the type of graft, using a propensity score analysis. In total population, grade II–IV and III–IV acute GVHD (aGVHD) were lower with BM than with PB. Grade III–IV aGVHD was lower with BM than with PB + ATG. All outcomes were similar in PB and PB + ATG groups. Then, in total population, adding ATG does not benefit the procedure. In acute leukemia, myelodysplastic syndrome and myeloproliferative syndrome (AL-MDS-MPS) subgroup receiving non-myeloablative conditioning, risk of relapse was twice greater with BM than with PB (51 vs. 22%, respectively). Conversely, risk of aGVHD was greater with PB (38% for aGVHD II–IV; 16% for aGVHD III–IV) than with BM (28% for aGVHD II–IV; 8% for aGVHD III–IV). In this subgroup with intensified conditioning regimen, risk of relapse became similar with PB and BM but risk of aGVHD III–IV remained higher with PB than with BM graft (HR = 2.0; range [1.17–3.43], p = 0.012).

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Section: Discussioncontrasting

confidence: 99%

Bone marrow graft versus peripheral blood graft in haploidentical hematopoietic stem cells transplantation: a retrospective analysis in1344 patients of SFGM-TC registry

Lacan,

Lambert,

Forcade

et al. 2024

J Hematol Oncol

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“…Various combinations of PTCy and ATG have been explored by several groups. Most combinations consisted of pre-transplant ATG and PTCy at varying doses, showing low rates of grade III-IV aGvHD and cGvHD along with amelioration of GRFS 9,[12][13][14][15] . The most common cause of death was infection in these regimens 12 .…”

Section: Discussionmentioning

confidence: 99%

Post-transplant cyclophosphamide at 80mg/kg with low dose post-engraftment anti-thymocyte globulin in haploidentical transplantation with myeloablative conditioning

Hu,

Wang,

et al. 2023

Preprint

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While post-transplant cyclophosphamide (PTCy) is commonly used as graft-versus-host disease (GvHD) prophylaxis in haploidentical stem cell transplantation (haplo-HSCT), the dose remains a matter of debate due to side effect concerns. Standard dose PTCy associated with tacrolimus and post-engraftment anti-thymocyte globulin (ATG) was used as the reference GvHD prophylaxis in our center and had demonstrated encouraging results. Though PTCy 80 mg/kg was shown to be feasible in patients in reduced intensity conditioning, whether it exerts equivalent GvHD prophylactic efficacy in myeloablative conditioning (MAC) setting has not been confirmed. Here, we retrospectively analyzed the efficacy and safety of PTCy 80mg/kg combined with tacrolimus and post-engraftment ATG as GvHD prophylaxis in patients aged more than 55 years or with cardiac antecedents or HCT-CI score > 2 undergoing haplo-HSCT with MAC. The cumulative incidence of grade III-IV aGvHD at day 100 and moderate-to-severe cGvHD at 1 year was 4.8%±3.4% and 19.9%±7.0%, respectively. When compared with patients receiving the reference regimen, patients from the PTCy 80mg/kg group had similar incidence of GvHDs and survival as their younger counterparts. Thus, PTCy 80 mg/kg seems to be feasible for patients treated with MAC conditioning regimens in haplo-HSCT, inviting further investigation notably in frail patients.

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“…In brief, calcineurin inhibitors with short-term methotrexate and mycophenolate mofetil were served as the backbone for the GvHD prophylaxis. Among all patients included in this analysis, anti-thymocyte globulin (ATG), posttransplant cyclophosphamide (PTCy), a combination of ATG and PTCy [ 27 ], and a combination of Cyclosporin A (CSA) and Methotrexate (MTX) were adapted for 37, 15, 118 and 3 patients, respectively. The stem cell sources were granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cell grafts from haploidentical related donors ( n = 134), HLA-matched related donors ( n = 22), and HLA-matched unrelated donors ( n = 17).…”

Section: Methodsmentioning

confidence: 99%

Early T-cell reconstitution predicts risk of EBV reactivation after allogeneic hematopoietic stem cell transplantation

Huang,

Pan,

Wang

et al. 2024

Clin Exp Med

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The quality of immune reconstitution (IR) is crucial for the outcome of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and is closely connected with infection, relapse and graft-versus-host disease (GvHD) which are the most important causes for transplantation failure. However, the IR pattern in the early stage after allo-HSCT, particularly haploidentical (HID) HSCT, remains unclear. In this retrospective study, we examined the T cell reconstitution of patients within the initial 30 days (n = 173) and 100 days (n = 122) after allo-HSCT with myeloablative condition (MAC), of which > 70% were HID HSCT, to assess the influence of IR on the transplant outcomes. By comparing 78 patients with good IR (GIR) to 44 patients with poor IR (PIR), we observed that GIR was associated with lower risk for Epstein–Barr virus (EBV) reactivation and cytomegalovirus (CMV) reactivation, but had no significant impacts on the survival outcomes (i.e., overall survival, event-free survival) and cumulative incidences of GvHD. Importantly, we found lymphocyte reconstitution pattern at day 30 after allo-HSCT would be a surrogate for IR evaluated at day 100. In the Cox proportional hazard model, early reconstitution of CD4+, CD4+CD25+, CD4+CD45RO+, CD4+CD25+CD27low, and CD8+ T cells at day 30 was reversely correlated with risk of EBV reactivation. Finally, we constructed a predictive model for EBV reactivation with CD8+ and CD4+CD45RO+ T cell proportions of the training cohort (n = 102), which was validated with a validation cohort (n = 37). In summary, our study found that the quality of IR at day 30 had a predictive value for the risk of EBV reactivation, and might provide guidance for close monitoring for EBV reactivation.

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Combining post-transplant cyclophosphamide with antithymocyte globulin for graft-versus-host disease prophylaxis in hematological malignancies

Cited by 18 publications

References 135 publications

Bone marrow graft versus peripheral blood graft in haploidentical hematopoietic stem cells transplantation: a retrospective analysis in1344 patients of SFGM-TC registry

Bone marrow graft versus peripheral blood graft in haploidentical hematopoietic stem cells transplantation: a retrospective analysis in1344 patients of SFGM-TC registry

Post-transplant cyclophosphamide at 80mg/kg with low dose post-engraftment anti-thymocyte globulin in haploidentical transplantation with myeloablative conditioning

Early T-cell reconstitution predicts risk of EBV reactivation after allogeneic hematopoietic stem cell transplantation

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