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.

Acute myocardial infarction as a finding of acute promyelocytic leukemia-related coagulation disorder.

Acute promyelocytic leukemia (APL) has one of the most favorable prognoses among other leukemia subtypes. However, the major cause of mortality in APL is disseminated intravascular coagulation at the presentation. We present a case of acute myocardial infarction (MI) at the time of APL diagnosis before treatment. The patient suffered from chest pain, sweating and giddiness. He was hypoxic, hypotensive and bradycardic. ECG showed inferior MI. Unfractioned heparin infusion (850 U/h) was started and 5 min after the previous ECG showed total ST resolution. We suggest that in this case, MI was not related to atherosclerotic plaque rupture but related to DIC manifestation.

Value of 18F-fluorodeoxyglucose uptake in positron emission tomography/computed tomography in predicting survival in multiple myeloma.

PURPOSE: We assessed the role of the maximum standardized uptake value (SUV(max)) of bone marrow and the extramedullary lesion with the highest SUV(max) in positron emission tomography/computed tomography (PET/CT) of newly diagnosed multiple myeloma (MM) patients in predicting overall survival (OS). METHODS: A total of 61 newly diagnosed patients (55 MM and 6 plasmacytoma) were enrolled in the study [37 men and 24 women with a median age of 57 years (range 28-80 years)]. The SUV(max) of bone marrow and the extramedullary lesion in PET/CT was correlated with the levels of ß(2)-microglobulin, C-reactive protein (CRP), albumin, creatinine, per cent of bone marrow plasma cells, serum free light chain (FLC) ratio, International Staging System (ISS) score and Durie-Salmon stage. RESULTS: The extramedullary lesion with the highest SUV(max) showed significant correlation with bone marrow fluorodeoxyglucose (FDG) uptake (p = 0.027) and near significant correlation with ISS (p = 0.048). Bone marrow SUV(max) correlated significantly with the per cent of bone marrow plasma cell count (p = 0.024), CRP (p = 0.012) and ISS (p = 0.013). In stage III MM the mean values of SUV(max) in extramedullary lesions were significantly higher than stages I and II (6.23 ± 6.32 vs 2.85 ± 3.44, p = 0.023). The serum FLC ratio did not show any correlation with SUV(max) of lesions and bone marrow (p > 0.05). Forty-four MM patients with FDG-positive lesions in PET/CT showed inferior 5-year estimated survival (61.73%) when compared to 11 patients without FDG-positive lesions, all of whom were alive (p = 0.01). In multivariate analysis an extramedullary lesion with the highest SUV(max) was the only independent predictor of OS (p = 0.03). CONCLUSION: PET/CT allows identification of high-risk myeloma patients, and extramedullary lesions with the highest SUV(max) independently predict inferior OS.

Free light chain: a novel predictor of adverse outcome in chronic lymphocytic leukemia.

OBJECTIVES: Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. This retrospective study is planned to assess the prognostic value of serum free light chain (sFLC) levels and FLC ratio (FLCR) in CLL. METHODS: Quantitative levels of sFLC were measured nephelometrically in sera collected at diagnosis. The expressions of ZAP70 and CD38 were quantified by flow cytometry. Chromosomal abnormalities were determined by interphase fluorescence in situ hybridization (FISH). RESULTS: In a cohort of 101 patients with a median follow-up of 29 (1-234) months, sFLC levels were found to be high in 55 patients (54.5%). An abnormal FLCR was found in 30 patients (29.7%). FISH-based genetic risk groups did not differ significantly with respect to sFLC and FLCR (P > 0.05). Median time to first treatment was shorter in patients with high sFLC levels (P = 0.02). Median overall survival (OS) was shorter in patients with high sFLC levels (P = 0.01) and abnormal FLCR (P = 0.05). In patients with early stage disease, median OS was shorter in high sFLC (P = 0.03) and abnormal FLCR groups (P = 0.048). A relationship was observed between abnormal sFLC levels and CD38 positivity on logistic regression analysis (P = 0.003; OR: 4.44; 95% CI: 1.66-11.8). CONCLUSIONS: This study highlighted the adverse prognostic impact of high sFLC levels and abnormal FLCR with regard to survival in CLL, even in early stage patients. Prospective studies are warranted to validate the adverse impact of sFLC and FLCR on clinical outcome.

Extranodal multifocal Rosai-Dorfman disease: response to 2-chlorodeoxyadenosine treatment.

Rosai-Dorfman disease (RDD) or "sinus histiocytosis with massive lymphadenopathy" is a rare lymphoproliferative disorder of unknown etiology. The disease usually presents with painless lymphadenopathy with occasional extranodal involvement in various organs. We report a case of a 36-year-old man with a history of non-Hodgkin lymphoma (NHL), who recently presented with inguinal lymphadenopathy. Following the diagnosis of RDD on lymph node biopsy, he developed symptoms of spinal cord compression due to a mass lesion discovered at T6-7 vertebral level. 18F-Fluorodeoxyglucose (18FDG) positron emission tomography (PET-CT) revealed extensive disease with lung, renal and bone involvement. The patient received a short course of steroid therapy for cord compression findings and 2-chlorodeoxyadenosine (2-CdA) treatment was initiated for long-term disease control. He had a dramatic sustained response to treatment with six courses of 2-CdA. These results suggest that 2-CdA can be an effective treatment of choice and positron emission tomography with 18FDG can be used for determining the extent of disease and for follow-up in RDD.