Patterns of infection and infection-related mortality in patients with steroid-refractory acute graft versus host disease.
This study aimed to characterize the incidence, etiology and outcome of infectious episodes in patients with steroid refractory acute GvHD (SR-GvHD). The cohort included 127 adults treated with inolimomab (77%) or etanercept (23%) owing to acute 2-4 SR-GvHD, with a response rate of 43% on day +30 and a 4-year survival of 15%. The 1-year cumulative incidences of bacterial, CMV and invasive fungal infection were 74%, 65% and 14%, respectively. A high rate (37%) of enterococcal infections was observed. Twenty patients (15.7%) developed BK virus-hemorrhagic cystitis and five percent had an EBV reactivation with only one case of PTLD. One-third of long-term survivors developed pneumonia by a community respiratory virus and/or encapsulated bacteria, mostly associated with chronic GvHD. Infections were an important cause of non-relapse mortality, with a 4-year incidence of 46%. In multivariate analysis, use of rituximab in the 6 months before SCT (hazard ratio; HR 4.2; 95% confidence interval; CI 1.1-16.3), severe infection before SR-GvHD onset (HR 5.8; 95% CI 1.3-26.3) and a baseline C-reactive protein >15 UI/mL (HR 2.9; 95% CI 1.1-8.5) were associated with infection-related mortality. High rates of opportunistic infections with remarkable mortality warrant further efforts to optimize long-term outcomes after SR-GvHD.
Hematology Department, Hospital de la Santa Creu i Sant Pau, José Carreras Leukemia Research Institute and IIB Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
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García-Cadenas
Hematology Department, Hospital Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Rivera
Hematology Department, Hospital de la Santa Creu i Sant Pau, José Carreras Leukemia Research Institute and IIB Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Martino
Hematology Department, Hospital de la Santa Creu i Sant Pau, José Carreras Leukemia Research Institute and IIB Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Esquirol
Hematology Department, Hospital Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Barba
Hematology Department, Hospital de la Santa Creu i Sant Pau, José Carreras Leukemia Research Institute and IIB Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Novelli
Hematology Department, Hospital Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Orti
Hematology Department, Hospital de la Santa Creu i Sant Pau, José Carreras Leukemia Research Institute and IIB Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Briones
Hematology Department, Hospital de la Santa Creu i Sant Pau, José Carreras Leukemia Research Institute and IIB Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Brunet
Hematology Department, Hospital Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Valcarcel
Hematology Department, Hospital de la Santa Creu i Sant Pau, José Carreras Leukemia Research Institute and IIB Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Sierra
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D000068800:Etanercept / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology / Q000401:mortality*; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D006801:Humans; D007239:Infections / Q000209:etiology / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation; D015996:Survival Rate
D000911:Antibodies, Monoclonal; C079843:inolimomab; D000068800:Etanercept