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Low-dose PTCy plus low-dose ATG as GVHD prophylaxis after UD-PBSCT for hematologic malignancies: a prospective, multicenter, randomized controlled trial
Zu, Y., Gui, R., Li, Z., Wang, J., Zhang, Y., Yu, F., Zhao, H., Zhan, X., Wang, Z., Xing, P., et al
Blood Cancer Journal. 2023;13(1):10
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The MAGIC algorithm probability (MAP)-guided preemptive therapy of acute graft versus host disease with methylprednisolone: A randomized controlled trial
Zeng, Q., Zhang, H., Kuang, P., Li, J., Chen, X., Dong, T., Wu, Q., Zhang, C., Chen, C., Niu, T., et al
American journal of hematology. 2023
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Editor's Choice
Abstract
Acute graft versus host disease (aGvHD) is a severe complication that arises in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and remains the primary cause of nonrelapse mortality (NRM). The MAGIC algorithm probability (MAP) has been proposed to identify patients at intermediate and high risk of developing aGvHD. The levels of suppression of tumorigenicity 2 (ST2) and regenerating islet-derived 3α (Reg3α) were assessed, and MAP was calculated on days 7, 14, 21, and 28 after allo-HSCT. Based on the MAP results, patients were classified into low-, intermediate-, or high-risk groups for the development of aGvHD. Random assignment was performed to allocate intermediate- or high-risk patients to receive preemptive therapy with methylprednisolone or not. The 100-day cumulative incidences of grade 2 or higher (35.5% ± 8.6%) and grade 3 or higher (12.9% ± 6.0%) aGvHD in the methylprednisolone group were significantly lower than those in the control group (66.7% ± 7.9%, p = .01; 42.9% ± 8.4%, p = .01), and similar to those observed in the low-risk group (31.7% ± 7.3%, p = .75; 2.4% ± 2.4%, p = .08). The 6-month cumulative incidences of NRM were 14.1% ± 6.6%, 22.7% ± 7.1%, and 2.4% ± 2.4% in the methylprednisolone, control, and low-risk groups, respectively, with no significant difference between the methylprednisolone and control groups (p = .29). Methylprednisolone did not increase infections (p = .34). The 100-day cumulative incidences of cytomegalovirus (CMV) reactivation were 67.7% ± 8.4%, 65.6% ± 8.4%, and 46.3% ± 7.8% (p = .08), and those of grade 2 or higher hemorrhagic cystitis were 29.0% ± 8.2%, 45.2% ± 8.9% and 22.0% ± 6.5% (p = .11) in the methylprednisolone, control, and low-risk groups, respectively. MAP-guided preemptive therapy for aGvHD is promising. The long-term efficacy and safety remain to be investigated.
PICO Summary
Population
Patients aged 16-65 years undergoing allo-HSCT and assessed as intermediate- or high-risk using the MAGIC algorithm (n=67)
Intervention
Pre-emptive therapy with methylprednisolone (n=31)
Comparison
Control: no methylprednisolone therapy (n=36)
Outcome
The 100-day cumulative incidences of grade 2 or higher (35.5% ± 8.6%) and grade 3 or higher (12.9% ± 6.0%) aGvHD in the methylprednisolone group were significantly lower than those in the control group (66.7% ± 7.9%, p = .01; 42.9% ± 8.4%), and similar to those observed in the low-risk group (31.7% ± 7.3%, p = .75; 2.4% ± 2.4%). The 6-month cumulative incidences of NRM were 14.1% ± 6.6%, 22.7% ± 7.1%, and 2.4% ± 2.4% in the methylprednisolone, control, and low-risk groups, respectively, with no significant difference between the methylprednisolone and control groups. Methylprednisolone did not increase infections. The 100-day cumulative incidences of cytomegalovirus (CMV) reactivation were 67.7% ± 8.4%, 65.6% ± 8.4%, and 46.3% ± 7.8%, and those of grade 2 or higher hemorrhagic cystitis were 29.0% ± 8.2%, 45.2% ± 8.9% and 22.0% ± 6.5% in the methylprednisolone, control, and low-risk groups, respectively.
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Are We Making PROGRESS in Preventing Graft-versus-Host Disease and Improving Clinical Outcomes? Impact of BMT CTN 1301 Study Results on Clinical Practice
Hamilton, B. K., Cutler, C., Divine, C., Juckett, M., LeMaistre, C., Stewart, S., Wilder, J., Horowitz, M., Khera, N., Burns, L. J.
Transplantation and cellular therapy. 2022
Abstract
The need for prospective randomized clinical trials investigating novel graft-versus-host disease (GVHD) prevention strategies which include other clinical outcomes impacted by GVHD has been highlighted as a priority for the field of hematopoietic cell transplantation. A recently completed study through the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 1301) comparing CD34+ selection and post-transplant cyclophosphamide to tacrolimus/methotrexate (Tac/MTX) for GVHD prevention demonstrated no significant differences in the primary endpoint of Chronic GVHD-Relapse-Free Survival (CRFS) among the three approaches. The trial did not demonstrate a superior approach compared to Tac/MTX; however, it highlights several challenges in determining the best and most relevant approaches to clinical trial design, particularly in the context of current and ongoing changes in real world practices. Here, we review BMT CTN 1301 results and implications for clinical practice and future clinical trial design.
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Posttransplant Cyclophosphamide for Prevention of Graft-versus-Host Disease: The Prospective Randomized HOVON-96 Trial
Broers, A. E. C., de Jong, C. N., Bakunina, K., Hazenberg, M. D., van Marwijk Kooy, M., de Groot, M., van Gelder, M., Kuball, J., van der Holt, B., Meijer, E., et al
Blood advances. 2022
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Editor's Choice
Abstract
Graft versus host disease (GVHD) is the most important complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). We performed a prospective randomized, multicenter, phase III trial to study whether posttransplant cyclophosphamide (PT-Cy) combined with a short course of cyclosporine A (CsA) would result in a reduction of severe GVHD and improvement of GVHD-free, relapse free survival (GRFS) as compared to the combination of CsA and mycophenolic acid (MPA) after non-myeloablative (NMA) matched related and unrelated peripheral blood alloHSCT. Between October 2013 and June 2018, 160 patients diagnosed with a high-risk hematological malignancy and having a matched related or at least 8 out of 8 HLA matched unrelated donor were randomized and allocated in a 1:2 ratio to CsA/MPA or PT-Cy/CsA. A total of 151 patients was transplanted (52 versus 99 patients). The cumulative incidence of grade II-IV acute GVHD at six months was 48% in recipients of CsA/MPA versus 30% following PT-Cy/CsA (Hazard ratio (HR): 0.48, 95% confidence interval (CI): 0.29-0.82, p=0.007). The two-year cumulative incidence of chronic extensive GVHD was 48% versus 16% (HR: 0.36, 95%CI: 0.21-0.64, p<0.001). The one-year estimate of GRFS was 21% (11%-32%) versus 45% (35%-55%), p<0.001. With a median follow-up of 56.4 months, relapse incidence, progression-free and overall survival were not significantly different between the two treatment arms. PT-Cy combined with a short course of CsA after NMA matched alloHSCT significantly improves GRFS due to a significant reduction in severe acute and chronic GVHD. The trial was registered as number NL2128 in the Dutch trial registry (www.trialregister.nl).
PICO Summary
Population
Patients with haematological malignancy due to undergo non-myeloablative allogeneic stem cell transplant with a matched related or at least 8/8 HLA matched unrelated donor, in six centres in the Netherlands (n=151)
Intervention
Posttransplant cyclophosphamide combined with a short course of cyclosporine A (PT-Cy/CsA, n=99)
Comparison
Cyclosporine A and mycophenolic acid (CsA/MPA, n=52)
Outcome
The cumulative incidence of grade II-IV acute GVHD at six months was 48% in recipients of CsA/MPA versus 30% following PT-Cy/CsA (Hazard ratio (HR): 0.48, 95% confidence interval (CI): 0.29-0.82). The two-year cumulative incidence of chronic extensive GVHD was 48% versus 16% (HR: 0.36, 95%CI: 0.21-0.64). The one-year estimate of GRFS was 21% (11%-32%) versus 45% (35%-55%), p<0.001. With a median follow-up of 56.4 months, relapse incidence, progression-free and overall survival were not significantly different between the two treatment arms.
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T-cell and cytokine dynamics in the blood of patients after hematopoietic stem cell transplantation and multipotent mesenchymal stromal cells administration
Petinati, N., Davydova, Y., Nikiforova, K., Bigildeev, A., Belyavsky, A., Arapidi, G., Drize, N., Kuzmina, L., Parovichnikova, E., Savchenko, V.
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Multipotent mesenchymal stromal cells (MSCs) are currently under intense investigation for treatment and prevention of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), owing to their substantial immunomodulatory properties. The responses of recipients to MSC infusion following allo-HSCT are not yet well understood. T-cells are central to the adaptive immune system, protecting organism from infection and malignant cells. Memory T-cells with different phenotypes, gene expression profiles and functional properties are critical for immune processes regulation. OBJECTIVE The aim of this work was to study the dynamics of memory T-cells subpopulations and cytokines in blood of allo-HSCT patients after MSCs administration. STUDY DESIGN In clinical trial NCT01941394 patients after allo-HSCT were randomized into two groups: the one receiving standard GVHD prophylaxis and another one receiving additionally MSCs infusion on the day of recovery of leukocytes to 1000 cells/μl (engraftment, day E0). The blood samples of patients from both groups were analyzed on days E0, E+3 and E+30. Subpopulations of T-cells were studied by flow cytometry and concentration of cytokines was evaluated by the Bio-Plex Pro Human Cytokine Panel. RESULTS Administration of MSCs to patients on day E0 did not affect the overall dynamics of restoration of absolute numbers and the proportion of T and B lymphocytes after 3 and 30 days. Three days after MSCs injection, only the numbers of CD8+ effector cells (CD8+TE, CD8+TM, CD8+EM) were found to increase significantly. Significant increase in a number of CD4+ cells after 30 days compared to day E0 was observed only in patients who received MSCs, which indicates a faster recovery of CD4+ cell population following MSC injection. Increase in CD8+ cell number by day E+30 was significant regardless of MSC administration. To characterize the immune status of patients following allo-HSCT in more detail, changes in the cytokine concentration in the peripheral blood of patients on days E0, E+3 and E+30 after the administration of MSCs were investigated. On day E+30, significant increase in the number of CD4+CM and activated CD4+CD25+ cells was observed. The concentration of pro- and anti-inflammatory cytokines IL-6, IL-8, IL-17, TNF-α and IFN-γ, significantly increased in patients injected with MSCs. Analysis of the growth factor levels showed that in the group of patients who received MSCs, the concentration of G-CSF, CM-CSF, PDGFbb, FGFb and IL-5 increased by day E+30. Among the cytokines involved in the regulation of the immune response, the concentration of IL-9, Eotaxin, IP-10, MCP-1, and MIP-1a increased after 30 days, regardless of the MSCs administration. CONCLUSION The administration of MSCs exerts a positive effect on restoration of T-cell subpopulations and recovery of immune system of patients after allo-HSCT.
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6.
Low-dose Thymoglobulin for prevention of chronic graft-versus-host disease in transplantation from an HLA-matched sibling donor
Cho, B. S., Min, G. J., Park, S. S., Yoon, S. Y., Park, S., Jeon, Y. W., Shin, S. H., Yahng, S. A., Yoon, J. H., Lee, S. E., et al
American journal of hematology. 2021
Abstract
Despite the proven efficacy of anti-T-cell or antithymocyte globulin (ATG) for chronic graft-versus-host disease (GVHD) prevention in transplantation from an unrelated donor, dosing protocols and the effects of ATG on relapse and infection remain controversial. In the setting of transplantation from an HLA-matched sibling (MSD-T), few randomized studies have been conducted. We conducted a prospective, single-center, open-label, randomized study of low-dose Thymoglobulin (2.5 mg/kg) for chronic GVHD prevention. A total of 120 patients with acute leukemia were randomly assigned in a 1:1 ratio. After a median follow-up of 27 months, the cumulative incidence of chronic GVHD in the ATG and non-ATG groups was 25.0% and 65.4% (P<0.001), respectively. The ATG group had an increased relapse rate compared with the non-ATG-group (20.0% vs 9.3%; P=0.055), with risks that differed according to cytogenetic subgroup (high-risk, 29.6% vs. 9.3%, P=0.042; non-high-risk, 12.2% vs. 9.2%, P=0.596). Chronic GVHD-free and relapse-free survival (cGRFS) was higher in the ATG group (46.7% vs. 19.4%; P=0.070), and the difference was significant in a cytogenetic non-high-risk subgroup (45.5% vs. 0%; P=0.038). No differences were observed in other survival outcomes. Improved physical components in quality-of-life scores were observed in the ATG group at 12 months after transplantation. A higher rate of Epstein-Barr virus reactivation was observed in the ATG group (21.8% vs. 5.1%; P=0.013), whereas no between-group differences for other complications. In conclusion, the low-dose Thymoglobulin effectively prevented chronic GVHD in MSD-T, resulting in improvement in quality-of-life and cGRFS, whereas the necessity of caution for high-risk acute leukemia. This article is protected by copyright. All rights reserved.
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7.
Combination of Low-Dose, Short-Course Mycophenolate Mofetil With Cyclosporine and Methotrexate for Graft-Versus-Host Disease Prophylaxis in Allogeneic Stem Cell Transplant
Ramzi, M., Haghighat, S., Namdari, N., Haghighinejad, H.
Experimental and Clinical Transplantation : Official Journal of the Middle East Society for Organ Transplantation. 2021;19(12):1328-1333
Abstract
OBJECTIVES With the standard regimen for graft-versushost disease prophylaxis in allogeneic stem cell transplant with human leukocyte antigen-matched donor, grade II-IV acute graft-versus-host disease occurs in 30% to 50% of sibling and up to 80% of unrelated recipients. Studies with limited patient numbers have shown efficacy and safety of mycophenolate mofetil for graft-versus-host disease prophylaxis. We investigated the effect of low-dose mycophenolate mofetil added to a standardized prophylaxis regimen for graft-versus-host disease in related human leukocyte antigen-matched allogeneic stem cell transplant. MATERIALS AND METHODS In this prospective randomized clinical trial, we compared cyclosporine and methotrexate versus the combination of cyclosporine, methotrexate, and mycophenolate mofetil in all patients who underwent human leukocyte antigencompatible related donor allogeneic stem cell transplant for acute leukemia during 3 years at the Bone Marrow Transplant Unit at Namazi Hospital, Shiraz University of Medical Sciences (Shiraz, Iran). RESULTS All 134 patients in both groups underwent successful engraftment. Recovery times for neutrophils and platelets were not significantly different between groups (P < .05). Incidence of acute graft-versus-host disease in the cyclosporine, methotrexate, and mycophenolate mofetil group was less than in the cyclosporine and methotrexate group (21.6% vs 40.9%; P = .041). Incidence of grade II-IV acute graftversus-host disease in the mycophenolate mofetil group was 15.2% versus the control group at 33% (P = .045). CONCLUSIONS Our single-center study suggests the combination of mycophenolate mofetil, cyclosporine, and methotrexate is superior to the standard regimen of cyclosporine and methotrexate for graft-versushost disease prophylaxis after human leukocyte antigen-matched related donor allogeneic stem cell transplant.
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Optimizing antithymocyte globulin dosing in haploidentical hematopoietic cell transplantation: long-term follow-up of a multicenter, randomized controlled trial
Wang, Y., Liu, Q. F., Lin, R., Yang, T., Xu, Y. J., Mo, X. D., Huang, X. J.
Science Bulletin. 2021;66(24):2498-2505
Abstract
Given that randomized studies testing the long-term impact of antithymocyte globulin (ATG) dosing are scarce, we report the results of an extended follow-up from the original trial. In our prospective, multicenter, randomized trial, 408 leukemia patients 14-65 years of age who underwent haploidentical hematopoietic cell transplantation (haplo-HCT) under our original "Beijing Protocol" were randomly assigned one-to-one to ATG doses of 7.5 mg/kg (n = 203, ATG-7.5) or 10 mg/kg (n = 205, ATG-10.0) at four sites. Extended follow-up (median 1968 d (range: 1300-2710 d) indicated comparable 5-year probabilities of moderate-to-severe chronic graft-versus-host disease (GVHD) (hazard ratio (HR): 1.384, 95% confidence interval (CI): 0.876-2.189, P = 0.164), nonrelapse mortality (HR: 0.814, 95% CI: 0.526-1.261, P = 0.357), relapse (HR: 1.521, 95% CI: 0.919-2.518, P = 0.103), disease-free survival (HR: 1.074, 95% CI: 0.783-1.473, P = 0.658), and GVHD-free/relapse-free survival (HR: 1.186, 95% CI: 0.904-1.555, P = 0.219) between groups (ATG-7.5 vs. ATG-10.0). The 5-year rate of late effects did not differ significantly. However, the cytomegalovirus/Epstein-Barr virus-related death rate was much higher in the ATG-10.0 cohort than in the ATG-7.5 cohort (9.8% vs. 1.5%; P = 0.003). In summary, patients undergoing haplo-HCT benefit from 7.5 mg/kg ATG compared to 10.0 mg/kg ATG based on a balance between GVHD and infection control. ATG (7.5 mg/kg) is potentially regarded as the standard regimen in the platform. These results support the optimization of ATG use in the "Beijing Protocol", especially considering the potential economic advantage in developing countries.
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A Phase 3 Double-Blind Study of the Addition of Tocilizumab versus Placebo to Cyclosporin/Methotrexate GvHD Prophylaxis
Kennedy, G., Tey, S. K., Buizen, L., Varelias, A., Gartlan, K. H., Curley, C., Olver, S., Chang, K., Butler, J., Misra, A., et al
Blood. 2021
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Editor's Choice
Abstract
We determined the efficacy of tocilizumab (TCZ) in preventing grade II-IV acute GVHD (aGVHD) in patients with acute-leukemia or myelodysplasia undertaking matched-related-sibling (MSD) or volunteer-unrelated-donor (VUD) allogeneic-SCT after myeloablative or reduced-intensity conditioning across five Australian centers. 145 patients (50 MSD, 95 VUD) were randomly assigned to placebo or TCZ on day-1. All patients received T-cell-replete PBSC grafts and GVHD-prophylaxis with cyclosporin/methotrexate. A planned sub-study analyzed the VUD cohort. With a median follow up of 746 days, the incidence of grade II-IV aGVHD at day 100 for the entire cohort was 36% versus 27% for placebo versus TCZ (HR 0.69; CI:0.38-1.26, p=0.23) and 45% versus 32% (HR 0.61; CI:0.31-1.22, p=0.16) for the VUD subgroup. The incidence of grade II-IV aGVHD at day 180 for the entire cohort was 40% versus 29% for placebo versus TCZ (HR 0.68; CI:0.38-1.22, p=0.19) and 48% versus 32% (HR 0.59; CI:0.30-1.16, p=0.13) for the VUD subgroup. Reductions in aGVHD were predominantly in grade II disease. A trend to improved aGVHD-free survival (aGVHD-FS) was noted in the TCZ-treated VUD subgroup, 52% versus 68% for placebo versus TCZ (p=0.13). For the entire cohort, transplant-related-mortality occurred in 8% versus 11% of placebo versus TCZ-treated patients respectively (p=0.56) and overall-survival was 79% versus 71% (p=0.27). Median day to neutrophil and platelet engraftment was delayed by 2-3 days in TCZ-treated patients while liver toxicity and infectious complications were similar between groups. In this phase-3 randomized, double-blind trial (ACTRN12614000266662), tocilizumab showed non-significant trends to reduced incidence of grade II-IV aGVHD and improved aGVHD-FS in recipients of HLA-matched VUD donors, but no improvements in long term-survival.
PICO Summary
Population
Patients with acute-leukemia or myelodysplasia undertaking matched-related-sibling (MSD) or volunteer-unrelated-donor (VUD) allogeneic-SCT (n=145)
Intervention
Tocilizumab on day -1
Comparison
Placebo on day-1
Outcome
With a median follow up of 746 days, the incidence of grade II-IV aGVHD at day 100 for the entire cohort was 36% versus 27% for placebo versus TCZ (HR 0.69) and 45% versus 32% (HR 0.61) for the VUD subgroup. The incidence of grade II-IV aGVHD at day 180 for the entire cohort was 40% versus 29% for placebo versus TCZ (HR 0.68) and 48% versus 32% (HR 0.59) for the VUD subgroup. Reductions in aGVHD were predominantly in grade II disease. A trend to improved aGVHD-free survival (aGVHD-FS) was noted in the TCZ-treated VUD subgroup, 52% versus 68% for placebo versus TCZ. For the entire cohort, transplant-related-mortality occurred in 8% versus 11% of placebo versus TCZ-treated patients respectively and overall-survival was 79% versus 71%. Median day to neutrophil and platelet engraftment was delayed by 2-3 days in TCZ-treated patients while liver toxicity and infectious complications were similar between groups.
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10.
Phase II Trial of Costimulation Blockade With Abatacept for Prevention of Acute GVHD
Watkins, B., Qayed, M., McCracken, C., Bratrude, B., Betz, K., Suessmuth, Y., Yu, A., Sinclair, S., Furlan, S., Bosinger, S., et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2021;:Jco2001086
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Editor's Choice
Abstract
PURPOSE Severe (grade 3-4) acute graft-versus-host disease (AGVHD) is a major cause of death after unrelated-donor (URD) hematopoietic cell transplant (HCT), resulting in particularly high mortality after HLA-mismatched transplantation. There are no approved agents for AGVHD prevention, underscoring the critical unmet need for novel therapeutics. ABA2 was a phase II trial to rigorously assess safety, efficacy, and immunologic effects of adding T-cell costimulation blockade with abatacept to calcineurin inhibitor (CNI)/methotrexate (MTX)-based GVHD prophylaxis, to test whether abatacept could decrease AGVHD. METHODS ABA2 enrolled adults and children with hematologic malignancies under two strata: a randomized, double-blind, placebo-controlled stratum (8/8-HLA-matched URD), comparing CNI/MTX plus abatacept with CNI/MTX plus placebo, and a single-arm stratum (7/8-HLA-mismatched URD) comparing CNI/MTX plus abatacept versus CNI/MTX CIBMTR controls. The primary end point was day +100 grade 3-4 AGVHD, with day +180 severe-AGVHD-free-survival (SGFS) a key secondary end point. Sample sizes were calculated using a higher type-1 error (0.2) as recommended for phase II trials, and were based on predicting that abatacept would reduce grade 3-4 AGVHD from 20% to 10% (8/8s) and 30% to 10% (7/8s). ABA2 enrolled 142 recipients (8/8s, median follow-up = 716 days) and 43 recipients (7/8s, median follow-up = 708 days). RESULTS In 8/8s, grade 3-4 AGVHD was 6.8% (abatacept) versus 14.8% (placebo) (P = .13, hazard ratio = 0.45). SGFS was 93.2% (CNI/MTX plus abatacept) versus 82% (CNI/MTX plus placebo, P = .05). In the smaller 7/8 cohort, grade 3-4 AGVHD was 2.3% (CNI/MTX plus abatacept, intention-to-treat population), which compared favorably with a nonrandomized matched cohort of CNI/MTX (30.2%, P < .001), and the SGFS was better (97.7% v 58.7%, P < .001). Immunologic analysis revealed control of T-cell activation in abatacept-treated patients. CONCLUSION Adding abatacept to URD HCT was safe, reduced AGVHD, and improved SGFS. These results suggest that abatacept may substantially improve AGVHD-related transplant outcomes, with a particularly beneficial impact on HLA-mismatched HCT.
PICO Summary
Population
Adults and children with haematologic malignancies enrolled in the ABA2 trial (n=185)
Intervention
8/8 matched unrelated donor transplantation with CNI/MTX plus abatacept prophylaxis (abatacept, n=73)
Comparison
CNI/MTX plus placebo (placebo, n=69); non-randomised cohort: 7/8 mismatched unrelated donor (7/8, n=43)
Outcome
ABA2 enrolled 142 recipients (8/8s, median follow-up = 716 days) and 43 recipients (7/8s, median follow-up = 708 days). RESULTS: In 8/8s, grade 3-4 AGVHD was 6.8% (abatacept) versus 14.8% (placebo). SGFS was 93.2% (CNI/MTX plus abatacept) versus 82% (CNI/MTX plus placebo). In the smaller 7/8 cohort, grade 3-4 AGVHD was 2.3% (CNI/MTX plus abatacept, intention-to-treat population), which compared favorably with a nonrandomized matched cohort of CNI/MTX (30.2%), and the SGFS was better (97.7% v 58.7%). Immunologic analysis revealed control of T-cell activation in abatacept-treated patients.