Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed, refractory, or ineligible, to an IMiD (Immunomodulatory Drug), with measurable disease and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T0). The median age at diagnosis was 58 years and time from diagnosis to T0 was 3.3 years. Following T0, 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (51%) including >=partial response in 69 (38%). The median overall survival and event free survival from T0 were 9 and 5 months respectively. This study confirms the poor outcome once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs.
To characterize the epidemiology and prognostic factors of invasive fusariosis in hematopoietic stem cell transplant (HSCT) recipients, the records of HSCT recipients from 9 hospitals (7 in Brazil and 2 in the United States) were retrospectively reviewed. Sixty-one cases were identified: 54 in allogeneic HSCT recipients and 7 in autologous HSCT recipients. The incidence of fusariosis among allogeneic HSCT recipients varied between a range of 4.21-5.0 cases per 1000 in human leukocyte antigen (HLA)--matched related transplant recipients to 20.19 cases per 1000 in HLA-mismatched transplant recipients. The median time period between transplantation and diagnosis of fusariosis was 48 days. Among allogeneic HSCT recipients, a trimodal distribution was observed: a first peak before engraftment, a second peak at a median of 62 days after transplantation, and a third peak >1 year after transplantation. The actuarial survival was 13% (median, 13 days). Persistent neutropenia was the single prognostic factor for death identified by multivariate analysis.
Summary:Engraftment syndrome (ES) is an increasingly reported complication of hematopoietic stem cell transplantation (HSCT). In order to better characterize the clinical criteria for the diagnosis of ES, we retrospectively analyzed 125 autologous HSCT recipients. ES was first defined as the presence of noninfectious fever plus skin rash. Patients with and without these findings were compared (univariate and multivariate analyses) regarding the presence of weight gain, hypoalbuminemia, pulmonary infiltrates, diarrhea, neurological manifestations and jaundice. The variables that are significantly more frequent in patients with fever and skin rash were incorporated in the definition criteria. The final diagnostic criteria were noninfectious fever plus any of the following: skin rash, pulmonary infiltrates or diarrhea. The incidence of ES was 20%. The single risk factor for ES by multivariate analysis was a diagnosis other than Hodgkin's disease (odds ratio 6.17, 95% confidence interval 1.38-27.78). Patients with ES received empirical antifungal therapy more frequently than patients without the syndrome (40 vs 19%, P ¼ 0.03), and had a longer duration of hospitalization (P ¼ 0.0007). The prospective application of these diagnostic criteria may have a favorable impact on the early diagnosis of the syndrome, with the initiation of corticosteroids and a reduction in the unnecessary use of antimicrobial agents.
Background Maintenance therapy following autologous stem cell transplantation can delay disease progression and prolong survival in multiple myeloma (MM). Ixazomib is ideally suited for maintenance therapy given its efficacy, convenient once-weekly oral dosing, and low toxicity profile. Methods The phase 3, double-blind, placebo-controlled, TOURMALINE-MM3 study randomised 656 patients with newly diagnosed MM from 227 clinical/hospital sites in 30 countries in Europe, the Middle East, Africa,
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