Outcomes of patients with invasive fusariosis who undergo further immunosuppressive treatments, is there a role for secondary prophylaxis?

BACKGROUND: Patients treated for invasive aspergillosis may relapse during subsequent periods of immunosuppression and should receive secondary prophylaxis. Little is known about the frequency of relapse and practices of secondary prophylaxis for invasive fusariosis (IF). OBJECTIVES: Evaluate practices of secondary prophylaxis and the frequency of relapse in patients who survived IF and were exposed to subsequent periods of immunosuppression. METHODS: Multicentre retrospective study of patients with haematological malignancies who developed IF, survived the initial fungal disease period, and were exposed to subsequent periods of immunosuppression. RESULTS: Among 40 patients, 35 received additional chemotherapy and developed neutropenia (median, 24 days; range, 4-104), and five received glucocorticoids for the treatment of graft-vs-host disease. Overall, 32 patients received secondary prophylaxis (voriconazole in 24) for a median of 112 days (range, 12-468). IF relapsed in five patients (12.5%): 2/8 (25%) not on prophylaxis and 3/32 (9.4%) receiving prophylaxis. Among 28 patients with disseminated IF, relapse occurred in 2/2 (100%) not on prophylaxis and in 3/26 (11.5%) on prophylaxis (P = 0.03). All patients who relapsed IF died. CONCLUSIONS: Patients with IF who survive the initial disease may relapse if exposed to subsequent episodes of immunosuppressive therapies. Secondary prophylaxis should be considered, especially if IF was disseminated.

Rabbit antithymocyte globulin dose does not affect response or survival as first-line therapy for acquired aplastic anemia: a multicenter retrospective study.

In a prospective randomized study, treatment for aplastic anemia (AA) with rabbit antithymocyte globulin (r-ATG) and cyclosporine showed inferior hematological response and survival in comparison to horse antithymocyte globulin (h-ATG) and cyclosporine. However, h-ATG was discontinued in most Asian, South American, and European countries, where r-ATG became the only ATG formulation available. We retrospectively evaluated consecutive patients with acquired AA who received either rabbit (n = 170) or horse (n = 85) ATG and cyclosporine for first-line treatment from 1992 to 2014 in seven referral centers in Brazil and Argentina. Overall response at 3 months was 17% (95%CI, 11-23%) for r-ATG and 44% (95%CI, 33-55%) for h-ATG (p < 0.001). At 6 months, it was 31% (95%CI, 34-39%) for r-ATG and 59% (95%CI, 48-69%) for h-ATG (p < 0.001). Overall survival at 5 years was 57% (95%CI, 47-65%) for r-ATG and 80% (95%CI, 69-87%) for h-ATG (log-rank = 0.001). Relapse was significantly higher in patients receiving h-ATG (28%; 95%CI, 17-43%) as compared to r-ATG (9.4%; 95%CI, 4-21%; log-rank, p = 0.01). The type of ATG was the only factor associated with both response and survival. The r-ATG dose varied from 1 to 5 mg/kg/day, but it did not correlate with outcomes. In summary, this is the largest multicenter study comparing the two ATG formulations in AA. Our results indicate that the dose of r-ATG does not influence hematologic response or survival in first-line therapy for acquired AA. Considering the toxicity and costs of r-ATG, our findings challenge its aggregate benefit to cyclosporine therapy and further strengthen that h-ATG should remain standard therapy in AA.

Predictors of early mortality after rabbit antithymocyte globulin as first-line treatment in severe aplastic anemia.

Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine. The incidence of death in 3 months following rabbit ATG therapy was 15.1% (28/185). Early mortality was mainly related to infectious complications, despite adequate antibiotic and/or antifungal treatment. Age > 35 years (odds ratio [OR] 5.06, P = 0.001) and baseline absolute neutrophil count (ANC) ≤ 0.1 × 109/L (OR 7.64, P < 0.001) were independent risk factors for early mortality after immunosuppressive therapy with this agent. Hematological response at 6 months was observed in only 29.7% of all patients. OS at 1 year after rabbit ATG was 75.3%; and age > 35 years (OR 1.88, P = 0.03), baseline ANC ≤ 0.1 × 109/L (OR 2.65, P < 0.001), and lack of response to rabbit ATG (OR 11.40, P < 0.001) were independently associated with mortality. Alternative strategies are needed for the treatment of SAA patients in countries were horse ATG is unavailable, particularly for those at high risk for early mortality after rabbit ATG due to a higher age and very low pre-treatment neutrophil count.