Cyclosporine A trough concentrations are associated with acute GvHD after non-myeloablative allogeneic hematopoietic cell transplantation

• Published in: PloS one Vol. 14; no. 3; p. e0213913
• Main Authors: de Kort, Elizabeth A, de Lil, Heleen S, Bremmers, Manita E J, van Groningen, Lenneke F J, Blijlevens, Nicole M A, Huls, Gerwin, Brüggemann, Roger J M, van Dorp, Suzanne, van der Velden, Walter J F M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.03.2019; Public Library of Science (PLoS)
• Subjects: Acute Disease; Adult; Aged; Analysis; Biology and Life Sciences; Bone marrow; Calcineurin Inhibitors - administration & dosage; Calcineurin Inhibitors - adverse effects; Calcineurin Inhibitors - blood; Cohort Studies; Complications and side effects; Cyclosporine - administration & dosage; Cyclosporine - adverse effects; Cyclosporine - blood; Cyclosporins; Decitabine; Electrolytes; Female; Graft vs Host Disease - blood; Graft vs Host Disease - etiology; Graft vs. host disease; Graft-versus-host reaction; Health aspects; Health risks; Hematologic Neoplasms - therapy; Hematology; Hematopoietic stem cell transplantation; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic stem cells; Humans; Hypomagnesemia; Hyponatremia; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - blood; Impact analysis; Incidence; Kidney - drug effects; Leukemia; Liver - drug effects; Lymphocytes; Magnesium deficiency; Male; Medical tests; Medicine and Health Sciences; Middle Aged; Mortality; Multivariate analysis; Netherlands; Operating systems (Software); Patients; Physical Sciences; Research and Analysis Methods; Retrospective Studies; Risk factors; Stem cell transplantation; Stem cells; Surgery; Survival; Toxicity; Transplantation; Transplantation, Homologous - adverse effects; Transplants & implants; Treatment Outcome; Urinalysis; Water-Electrolyte Imbalance - etiology; Working groups; Young Adult; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0213913

Low plasma CsA concentrations (<300-350 ng/mL) early following allogeneic hematopoietic stem cell transplantation (HSCT) is associated with an increased risk of developing acute graft-versus-host disease (aGvHD). Nevertheless, the current optimal target trough concentration for CsA following HSCT is considered to be 200-400 ng/mL. Here, we performed a retrospective analysis of a homogeneous group of 129 patients who received HSCT after non-myeloablative conditioning, and we analyzed the impact of CsA trough concentration measured during the first four weeks (CsA W1-4) on the incidence aGvHD, relapse-free survival (RFS), non-relapse mortality (NRM), overall survival (OS), and toxicity. The 180-day incidence of grade II-IV aGvHD was 25% (32/129 patients). In multivariate analysis the incidence of grade II-IV aGvHD was significantly lower among patients with a CsA W1-4 concentration ≥350 ng/mL compared to patients with a concentration <350 ng/mL (18% versus 38%, respectively; P = 0.007), with a hazard ration (HR) of 0.38 (95% CI: 0.19-0.77). In contrast, we found no correlation between CsA trough concentration and RFS, NRM, or OS. Moreover, we found an increased incidence of hypomagnesemia at higher CsA concentrations, but no difference in the incidence of acute renal toxicity, hepatic toxicity, or electrolyte imbalance. Interestingly, 30% of patients experienced hyponatremia with no apparent cause other than the use of CsA, with urinalysis suggesting SIADH as the underlying cause. Our findings suggest that a CsA trough concentration of 350-500 ng/mL might be more appropriate in the first month following non-myeloablative HSCT.