Multicentric Castleman disease (MCD) describes a heterogeneous group of disorders involving systemic inflammation, characteristic lymph node histopathology, and multi-organ dysfunction because of pathologic hypercytokinemia. Whereas Human Herpes Virus-8 (HHV-8) drives the hypercytokinemia in a cohort of immunocompromised patients, the etiology of HHV-8-negative MCD is idiopathic (iMCD). Recently, a limited series of iMCD cases in Japan sharing a constellation of clinical features, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been described as TAFRO syndrome. Herein, we report clinicopathological findings on 25 patients (14 males and 11 females; 23 Japanese-born and two US-born), the largest TAFRO syndrome case series, including the first report of cases from the USA. The median age of onset was 50 years old (range: 23-72). The frequency of each feature was as follows: thrombocytopenia (21/25), anasarca (24/25), fever (21/25), organomegaly (25/25), and reticulin fibrosis (13/16). These patients frequently demonstrated abdominal pain, elevated serum alkaline phosphatase levels, and acute kidney failure. Surprisingly, none of the cases demonstrated marked hypergammoglobulinemia, which is frequently reported in iMCD. Lymph node biopsies revealed atrophic germinal centers with enlarged nuclei of endothelial cells and proliferation of endothelial venules in interfollicular zone. 23 of 25 cases were treated initially with corticosteroids; 12 patients responded poorly and required further therapy. Three patients died during the observation period (median: 9 months) because of disease progression or infections. TAFRO syndrome is a unique subtype of iMCD that demonstrates characteristic clinicopathological findings. Further study to clarify prognosis, pathophysiology, and appropriate treatment is needed.

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Invasive fungal infection (IFI) causes morbidity and mortality among patients with hematological malignancies who receive cytotoxic chemotherapy or hematopoietic stem cell transplantation (HSCT). We evaluated the incidence and treatment outcomes of proven and probable IFI in 22 institutions between 2006 and 2008 following the recent European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) consensus criteria. We analyzed 2,821 patients with hematological malignancies, including 597 who had undergone HSCT; these included patients with acute leukemia (n = 697), myelodysplastic syndrome (n = 284), lymphoma (n = 1465), or multiple myeloma (n = 375). IFIs were diagnosed in 38 (1.3%) patients (18 proven and 20 probable), including 20 patients who underwent HSCT and 18 who received chemotherapy alone; these included patients with aspergillosis (n = 23), candidiasis (n = 6), mucormycosis (n = 6), trichosporonosis (n = 2), and geotrichosis (n = 1). The incidence of IFI was 5.4 % in allogeneic HSCT patients, 0.4 % in autologous HSCT patients, and 0.8 % in patients receiving chemotherapy alone. Eighteen patients with aspergillosis were diagnosed with probable pulmonary IFI as determined by computed tomography scan and positive galactomannan assay. Overall, antifungal targeted therapies resulted in successful outcomes in 60.0 % of patients. IFI-attributable mortality rate was higher in HSCT patients than in those receiving chemotherapy alone, but the difference was not statistically significant.

SummaryThis study evaluated the clinical features of 276 patients with aggressive adult T-cell leukaemia-lymphoma (ATL) in 3 Japan Clinical Oncology Group (JCOG) trials. We assessed the long-term survivors who survived >5 years and constructed a prognostic index (PI), named the JCOG-PI, based on covariates obtained by Cox regression analysis. The median survival time (MST) of the entire cohort was 11 months. In 37 patients who survived >5 years, no disease-related deaths in 10 patients with lymphomatype were observed in contrast to the 10 ATL-related deaths in other types. In multivariate analysis of 193 patients, the JCOG-PI based on corrected calcium levels and performance status identified moderate and high risk groups with an MST of 14 and 8 months respectively (hazard ratio, 1Á926). The JCOG-PI was reproducible in an external validation. Patients with lymphoma-type who survived >5 years might have been cured. The JCOG-PI is valuable for identifying patients with extremely poor prognosis and will be useful for the design of future trials combining new drugs or investigational treatment strategies.