Dataset Information

Higher cyclosporine-A concentration increases the risk of relapse in AML following allogeneic stem cell transplantation from unrelated donors using anti-thymocyte globulin.

ABSTRACT: Cyclosporine-A (CsA) is used to prevent acute graft-versus-host disease (aGvHD). European Society for Blood and Marrow transplantation (EBMT) recommends a CsA target serum concentration of 200-300 µg/L during the first month after allogeneic hematopoietic stem cell transplantation (HSCT). With this study, we investigated whether a median CsA concentration > 200 µg/L (CsA_high) the first month after HSCT, compared to ≤ 200 µg/L (CsA_low), increased the relapse risk of acute myloid leukemia (AML), using unrelated donors (URD) and antithymocyte globulin (ATG). Data was collected from 157 patients with AML, transplanted 2010-2016. The cumulative incidence of relapse (CIR) at 60 months was 50% in the CsA_high versus 32% in the CsA_low group (p = 0.016). In univariate analysis, CsA_high versus CsA_low (p = 0.028), 10-unit increase of CsA as a continuous variable (p = 0.017) and high risk disease (p = 0.003) were associated with higher CIR. The results remained after adjusting for disease risk. Death following relapse occurred more frequently in the CsA_high group (p = 0.0076). There were no significant differences in rates of aGvHD, chronic GvHD (cGvHD), EBV/CMV-infections or overall survival (OS) between the two groups. In conclusion, we found that a median CsA concentration > 200 µg/L, the first month after HSCT, results in higher CIR of AML when combined with ATG.

SUBMITTER: Lisak M

PROVIDER: S-EPMC10733303 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Higher cyclosporine-A concentration increases the risk of relapse in AML following allogeneic stem cell transplantation from unrelated donors using anti-thymocyte globulin.

Lisak Mikael M Nicklasson Malin M Palmason Robert R Wichert Stina S Isaksson Cecila C Andersson Per-Ola PO Johansson Jan-Erik JE Lenhoff Stig S Brune Mats M Hansson Markus M

Scientific reports 20231220 1

Cyclosporine-A (CsA) is used to prevent acute graft-versus-host disease (aGvHD). European Society for Blood and Marrow transplantation (EBMT) recommends a CsA target serum concentration of 200-300 µg/L during the first month after allogeneic hematopoietic stem cell transplantation (HSCT). With this study, we investigated whether a median CsA concentration > 200 µg/L (CsA<sub>high</sub>) the first month after HSCT, compared to ≤ 200 µg/L (CsA<sub>low</sub>), increased the relapse risk of acute my ...[more]

PMID: 38123675

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Project description:BackgroundPost-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are both common graft-versus-host disease (GVHD) prophylaxis strategies in allo-HSCT from unrelated donors. However, no consensus has reached on which regimen is optimal. Although several studies concerning this topic exist, the outcomes of different studies still conflict with each other. Therefore, an overall comparison of the two regimens is urgently needed to help make informed clinical decisions.MethodsStudies comparing PTCy and ATG regimens in unrelated donor (UD) allo-HSCT were searched in four critical medical databases from inception to April 17, 2022. The primary outcome was grade II-IV aGVHD, grade III-IV aGVHD and chronic GVHD (cGVHD), and the secondary outcomes included overall survival (OS), relapse incidence (RI), non-relapse mortality (NRM), and several severe infectious complications. The quality of articles was assessed by the Newcastle-Ottawa scale (NOS), and data were extracted by two independent investigators and then analyzed by RevMan 5.4.ResultsSix out of 1091 articles were eligible for this meta-analysis. Compared with the ATG regimen, prophylaxis based on PTCy achieved a lower incidence of grade II-IV aGVHD incidence (RR=0.68, 95% CI 0.50-0.93, P=0.010, I 2 = 67%), grade III-IV aGVHD (RR=0.32, 95% CI 0.14-0.76, P=0.001, I 2 = 75%), NRM (RR=0.67, 95% CI 0.53-0.84, P=0.17, I 2 = 36%), EBV-related PTLD (RR=0.23, 95% CI 0.09-0.58, P=0.85, I 2 = 0%) and better OS (RR=1.29, 95% CI 1.03-1.62, P=0.0001, I 2 = 80%). The cGVHD, RI, CMV reactivation and BKV-related HC showed no significant difference between the two groups (RR=0.66, 95% CI 0.35-1.26, P<0.00001, I 2 = 86%; RR=0.95, 95% CI 0.78-1.16, P=0.37, I 2 = 7%; RR=0.89, 95% CI 0.63-1.24, P=0.07, I 2 = 57%; RR=0.88, 95% CI 0.76-1.03, P=0.44, I 2 = 0%).ConclusionIn the setting of unrelated donor allo-HSCT, prophylaxis based on PTCy can lower the incidence of grade II-IV aGVHD, grade III-IV aGVHD, NRM and EBV-related complication, achieve better OS compared to ATG-based regimen. And cGVHD, RI, CMV reactivation and BKV-related HC were comparable in the two groups.

Project description:ImportanceMatched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear.ObjectiveTo investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs.Design, setting, and participantsThis retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020.Interventions/exposuresAllo-HCT from an older MSD (donor age ≥50 years) or a younger MUD (donor age ≤35 years).Main outcomes and measuresThe primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival.ResultsOf 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P = .02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P = .07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P < .001), lower nonrelapse mortality (HR, 0.76; 95% CI, 0.59-0.96; P = .02), lower acute GVHD (HR, 0.52; 95% CI, 0.42-0.65; P < .001), chronic GVHD (HR, 0.77; 95% CI, 0.64-0.92; P = .005), and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42; 95% CI, 1.02-1.98; P = .04).Conclusions and relevanceThis cohort study found higher disease-free survival and lower relapse for allo-HCT in myelodysplastic syndrome using younger MUDs compared with older MSDs. The risk of nonrelapse mortality and GVHD was lower with older MSDs. These results suggest that the use of younger MUDs should be considered in the donor selection algorithm for myelodysplastic syndrome, in which it is pivotal to minimize relapse given limited treatment options for managing relapsed disease.

Project description:Although allogeneic hematopoietic cell transplantation (alloHCT) offers cure for older patients with acute lymphoblastic leukemia (ALL), disease relapse remains a major issue. Whether matched sibling donors (MSDs) are still the preferred donor choice compared to younger matched unrelated donors (MUDs) in the contemporary era of improved transplantation practices remains unknown. This retrospective cohort registry study queried the Center for International Blood and Marrow Transplant Research (CIBMTR) database in patients with B cell ALL (B-ALL) age ≥ 50 years undergoing alloHCT from older MSDs (age ≥ 50 years) or younger MUDs (age ≤ 35 years) between 2011 and 2018. The study included common allograft types, conditioning regimens, and graft-versus-host disease (GVHD) prophylaxis strategies. The primary outcome was relapse risk, and secondary outcomes included nonrelapse mortality (NRM), GVHD, leukemia-free survival (LFS), and overall survival (OS). Among 925 eligible patients in the study cohort, 386 underwent alloHCT with an older MSD (median donor age, 58 years) and 539 underwent alloHCT from a younger MUD (median donor age, 25 year). In multivariable analysis, younger MUDs conferred a significantly decreased risk of relapse (hazard ratio [HR], .68; P = .002) compared with older MSDs. The adjusted cumulative incidence of relapse at 5 years was significantly lower with younger MUDs than with older MSDs (26% versus 37%; P = .001). Younger MUDs were associated with a greater risk of chronic GVHD compared to older MSDs (HR, 1.33; 95% confidence interval [CI], 1.10 to 1.61; P = .003). Compared to older MSDs, younger MUDs conferred an increased NRM (HR, 1.38; P = .02) and higher adjusted cumulative incidence of NRM at 5 years (31% versus 22%; P = .006). There were no differences in post-alloHCT OS or LFS rates between younger MUDs and older MSDs (OS: HR, 1.09; [P = .37]; LFS: HR, .95 [P = .57]). The use of younger MUDs could be considered as a possible way to prevent relapse after alloHCT in older adults with ALL. Combining the use of younger MUDs with improved strategies to reduce GVHD merits further exploration to improve outcomes.

Dataset Information

Higher cyclosporine-A concentration increases the risk of relapse in AML following allogeneic stem cell transplantation from unrelated donors using anti-thymocyte globulin.

Publications

Higher cyclosporine-A concentration increases the risk of relapse in AML following allogeneic stem cell transplantation from unrelated donors using anti-thymocyte globulin.

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