Secondary antifungal prophylaxis in allogeneic hematopoietic stem cell transplant recipients with invasive fungal infection.

INTRODUCTION: Invasive fungal infection (IFI) is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. A previous history of IFI is not an absolute contraindication for allo-HSCT, particularly in the era of secondary antifungal prophylaxis (SAP). Prompt diagnosis and therapy are essential for HSCT outcome. METHODOLOGY: The charts of 58 allo-HSCT recipients [median age:29.5 (16-62); M/F:41/17] who had a previous history of IFI were retrospectively reviewed. RESULTS: Possible IFI was demonstrated in 32 (55.2%), probable in 13 (22.4%) and proven in 13 patients (22.4%). All patients received SAP [liposomal amphoterisin B (n ꞊ 35), voriconazole (n ꞊ 17), caspofungin (n ꞊ 2), posaconazole (n ꞊ 1), combination therapy (n = 3)] which was started on the first day of the conditioning regimen. Treatment success was better in the voriconazole group when compared to the amphotericin B arm (100% vs 69.2%; p = 0.029). Development of breakthrough IFI was more frequent in patients on amphotericin B prophylaxis (42.4% vs 23.1%; p = 0.036). Clinical and radiological response were achieved in 13 of 18 patients (72.2%) who developed breakthrough infection. Overall survival of the study population was 13.5% at a median follow-up of 154 (7-3285) days. Fungal mortality was found to be 23%. Overall survival was better in the voriconazole arm, without statistical significance (90% vs 65.8%, p > 0.05). CONCLUSIONS: Secondary antifungal prophylaxis is considered to be an indispensible strategy in patients with pre-HSCT IFI history. Voriconazole seems to be a relatively better alternative despite an underlying necessity of larger prospective trials.

Tuberculosis reactivation related with ruxolitinib in a patient with primary myelofibrosis.

Primary myelofibrosis (PMF) is a clonal stem cell disease, characterized by bone marrow fibrosis. Ruxolitinib is a selective inhibitor of JAK-1 and JAK-2 used to treat PMF. Its mechanism of action is based on the reduction of signal transduction and cytokine levels; including IL-6 and tumor necrosis factor alpha. Increased infection risk related to Ruxolutinib is rarely reported. Here we describe a case of tuberculosis infection ractivation in a female patient treated with Ruxolitinib. During the treatment, she complained of night sweats, weight loss and enlarged mass in the neck. Excisional mass biopsy revealed a necrotizing granulomatous lymphadenitis. QuantiFERON-TB and PPD tests were not able to diagnose the tuberculosis infection. Therapy with Ruxolitinib was interrupted due to possible immunsuppressive effects and the patient was treated with the standard antituberculosis regimen. After six months, the patient's symptoms had resolved and there was no lymphoadenopathy. In conclusion, it is important to assess the risk of tuberculosis activation before Ruxolitinib treatment. In addition, the diagnosis of tuberculosis using QuantiFERON-TB and PPD may be misleading in patients treated with Ruxolutinib.