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

Irene García Cadenas,Rodrigo Martino,Jorge Sierra,Ana Garrido,Salut Brunet,Javier Briones,Miquel Granell,Silvana Novelli,David Valcarcel,Carol Moreno,Pere Barba,J L Piñana,Albert Esquirol,Silvana Saavedra

doi:10.1155/2014/620682

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.

Highlights

Myeloablative allogeneic hematopoietic cell transplantation is the standard of care therapy for patients with several hematologic malignancies, but its high treatment-related mortality (TRM) frequently counterbalances its beneficial effects
We analyze the impact of cyclosporine (CsA) levels in the development of acute graft-versus-host disease after reduced intensity conditioning allogeneic hematopoietic transplantation
The current study found that, despite close surveillance, the median CsA levels were outside the desired range in a proportion of patients during the early posttransplant period

Summary

Introduction

Myeloablative allogeneic hematopoietic cell transplantation is the standard of care therapy for patients with several hematologic malignancies, but its high treatment-related mortality (TRM) frequently counterbalances its beneficial effects. Early TRM is reduced with RIC regimens, the development of graft-versus-host disease (GVHD) remains an important cause of transplant related morbidity and mortality [1,2,3]. Several studies on myeloablative conditioning allogeneic transplantation have shown that low whole blood concentrations of CsA during the periengraftment period can strongly affect the incidence of grade 2–4 acute GVHD (aGVHD) [5, 6]. This study evaluated the impact of CsA levels on the development of moderate to severe aGVHD, TRM, Mediators of Inflammation and overall survival (OS) in a cohort of consecutive HLAidentical sibling allo-RIC recipients

Methods

Results

Conclusion