Impact of Cyclosporine Levels on the Development of Acute Graft versus Host Disease after Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation

Abstract

We analyze the impact of cyclosporine (CsA) levels in the development of acute graft-versus-host disease (aGVHD) after reduced intensity conditioning allogeneic hematopoietic transplantation (allo-RIC). We retrospectively evaluated 156 consecutive patients who underwent HLA-identical sibling allo-RIC at our institution. CsA median blood levels in the 1st, 2nd, 3rd and 4th weeks after allo-RIC were 134 (range: 10–444), 219 (54–656), 253 (53–910) and 224 (30–699) ng/mL; 60%, 16%, 11% and 17% of the patients had median CsA blood levels below 150 ng/mL during these weeks. 53 patients developed grade 2–4 aGVHD for a cumulative incidence of 45% (95% CI 34–50%) at a median of 42 days. Low CsA levels on the 3rd week and sex-mismatch were associated with the development of GVHD. Risk factors for 1-year NRM and OS were advanced disease status (HR: 2.2, P = 0.02) and development of grade 2–4 aGVHD (HR: 2.5, P < 0.01), while there was a trend for higher NRM in patients with a low median CsA concentration on the 3rd week (P = 0.06). These results emphasize the relevance of sustaining adequate levels of blood CsA by close monitoring and dose adjustments, particularly when engraftment becomes evident. CsA adequate management will impact on long-term outcomes in the allo-RIC setting.

Premature cyclosporine cessation and TBI-containing conditioning regimen increase therisk ofacute GvHD in children undergoing unrelated donor hematopoietic stem cell transplantation

“…Another great part of the literature proves that a low plasma concentration level of CsA, especially in the early period post-HSCT (i.e., 2-3 weeks post-HSCT) is associated with a much higher risk of aGvHD. 26,[32][33][34][35] To our knowledge, this is the only study providing results that refer to the influence of early cessation of CsA on the occurrence of aGvHD. There is only one reference regarding premature discontinuation of CsA -the research conducted by Cadenas et al 32 Although this study was performed on a completely different population of patients, it contains a brief suggestion that there is no connection between discontinuation of CsA and aGvHD.…”

Low cyclosporine concentrations in children and time to acute graft versus host disease

“…Recent study authors have reported that high CsA concentrations within three to four weeks after transplantation are more effective in preventing aGVHD. For instance, Garcia et al [18] reported a correlation between CsA concentration and aGVHD in an adult patient with 156 allogenic HSCTs; low…”

Cyclosporine Plus Methotrexate or Cyclosporine Plus Mycophenolate Mofetil as Graft Versus Host Disease Prophylaxis in Acute Leukemia Transplant: Comparison of Toxicity, Engraftment Kinetics and Transplant Outcome

“…These include use of immunosuppressive drugs singly and in combination [14,15], tailoring the dose of CsA depending on blood levels [16,17] and evaluation of newer immunosuppressive agents in comparison with standard agents [5][6][7][8][9][10]. CsA combined with either MTX or MMF is the most widely used immunosuppressive drug [5,6,8].…”

“…Engraftment: Time to myeloid engraftment was defined as first of 3 consecutive days with an absolute neutrophil count of C0.5 9 10 9 /L [17]. Time to platelet engraftment was defined as first of 7 consecutive days when the platelet count is maintained C 20 9 10 9 /L without platelet transfusion.…”