title: 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.
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits, Institut Josep Carreras, Mas Casanovas 90, 08025 Barcelona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: García Cadenas
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits, Institut Josep Carreras, Mas Casanovas 90, 08025 Barcelona, Spain ; Hematology Department, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Valcarcel
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits, Institut Josep Carreras, Mas Casanovas 90, 08025 Barcelona, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Martino
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits, Institut Josep Carreras, Mas Casanovas 90, 08025 Barcelona, Spain ; Hematology Department, Hospital Clínic de Valencia, Valencia, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Piñana
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits, Institut Josep Carreras, Mas Casanovas 90, 08025 Barcelona, Spain ; Hematology Department, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Barba
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits, Institut Josep Carreras, Mas Casanovas 90, 08025 Barcelona, Spain.
authors.forename: Silvana
authors.initials: S
authors.lastname: Novelli
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits, Institut Josep Carreras, Mas Casanovas 90, 08025 Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Esquirol
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits, Institut Josep Carreras, Mas Casanovas 90, 08025 Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Garrido
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits, Institut Josep Carreras, Mas Casanovas 90, 08025 Barcelona, Spain.
authors.forename: Silvana
authors.initials: S
authors.lastname: Saavedra
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits, Institut Josep Carreras, Mas Casanovas 90, 08025 Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Granell
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits, Institut Josep Carreras, Mas Casanovas 90, 08025 Barcelona, Spain.
authors.forename: Carol
authors.initials: C
authors.lastname: Moreno
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits, Institut Josep Carreras, Mas Casanovas 90, 08025 Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Briones
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits, Institut Josep Carreras, Mas Casanovas 90, 08025 Barcelona, Spain.
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits, Institut Josep Carreras, Mas Casanovas 90, 08025 Barcelona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016572:Cyclosporine / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D006680:HLA Antigens / Q000737:chemistry; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000009:adverse effects* / Q000379:methods; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine