British journal of haematology
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Multicenter Study Controlled Clinical Trial
Transfusion of prion-filtered red cells does not increase the rate of alloimmunization or transfusion reactions in patients: results of the UK trial of prion-filtered versus standard red cells in surgical patients (PRISM A).
This study, conducted for the UK Blood Transfusion Services (UKBTS), evaluated the clinical safety of red cells filtered through a CE-marked prion removal filter (P-Capt™). Patients requiring blood transfusion for elective procedures in nine UK hospitals were entered into a non-randomized open trial to assess development of red cell antibodies to standard red cell (RCC) or prion-filtered red cell concentrates (PF-RCC) at eight weeks and six months post-transfusion. Patients who received at least 1 unit of PF-RCC were compared with a control cohort given RCC only. ⋯ There was no difference in transfusion reactions between arms, and no novel transfusion-related adverse events clearly attributable to PF-RCC were seen. These data suggest that prion filtration of red cells does not reduce overall transfusion safety. This finding requires confirmation in large populations of transfused patients.
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Multicenter Study
A prospective, international phase 2 study of bortezomib retreatment in patients with relapsed multiple myeloma.
Multiple myeloma (MM) typically follows a relapsing course with many patients requiring multiple therapies. This single-arm phase 2 study prospectively evaluated the efficacy and safety of bortezomib retreatment in MM patients who had relapsed after achieving at least a partial response (≥ PR) to prior bortezomib-based therapy. Patients aged ≥ 18 years, with measurable, secretory MM, who relapsed ≥ 6 months after prior bortezomib treatment were eligible. ⋯ Thrombocytopenia was the most common grade ≥ 3 AE (35%). Forty percent of patients experienced neuropathy events, which improved and resolved in a median of 1.5 and 8.9 months, respectively. In conclusion, bortezomib retreatment was effective and tolerable in relapsed MM patients, with no evidence of cumulative toxicities.
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To assess whether Haemocomplettan(®) (fibrinogen concentrate) or Fibrogammin(®) (Factor XIII concentrate) can be used to manage bleeding complications of antithrombotic treatment, we examined a normal plasma pool spiked with AR-H067637 (thrombin inhibitor) or rivaroxaban (activated factor X-inhibitor), to which one of the concentrates was added. Fibrin network permeability (Ks), images of Scanning Electron Microscopy (SEM) and Clot Lysis Time (CLT) were examined. Both inhibitors increased the Ks levels, which could be fully or partly reversed by Haemocomplettan(®) or Fibrogammin(®) respectively. ⋯ Tranexamic acid at a very low concentration (0·4 mg/ml) aided the two concentrates to stabilize the clots, where the prolongation of CLT was more pronounced for a lower dose than a higher dose of Haemocomplettan(®) while Fibrogammin(®) brought the greatest delay to CLT out of all additions. These observations were partly supported by SEM images, displaying alterations of fibrin fibre arrangement known to influence fibirinolysis. The in vitro data suggest that Haemocomplettan(®) or Fibrogammin(®) given in combination with a mini dose of tranexamic acid may slow down the natural clearance of fibrin clot by plasmin and thus prevent patients from haemorrhagic complications during antithrombotic therapy.
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Next-generation sequencing platforms have evolved to provide an accurate and comprehensive means for the detection of molecular mutations in heterogeneous tumour specimens. Here, we review the feasibility and practicality of this novel laboratory technology. ⋯ We also discuss deep-sequencing strategies to analyse the constantly increasing number of molecular markers applied for disease classification, patient stratification and individualized monitoring of minimal residual disease. Although many facets of this assay need to be taken into account, amplicon deep-sequencing has already demonstrated a promising technical performance and is being continuously developed towards routine application in diagnostic laboratories so that an impact on clinical practice can be achieved.
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Following reduced intensity-conditioned allogeneic stem cell transplantation (RIC allo-SCT) for chronic lymphocytic leukaemia (CLL), there is an inverse relationship between relapse and extensive chronic graft-versus-host disease (GVHD). We evaluated outcomes in 50 consecutive patients with CLL using the approach of alemtuzumab-based RIC allo-SCT and pre-emptive donor lymphocyte infusions (DLI) for mixed chimerism or minimal residual disease (MRD), with the intention of reducing the risk of GVHD. Forty two patients had high-risk disease, including 30% with 17p deletion (17p-). ⋯ DLI was associated with a 29% cumulative incidence of severe GVHD and mortality of 6.4%. At last follow-up, 83% of patients in CR were off all immunosuppressive treatment. In conclusion, the directed delivery of allogeneic cellular therapy has the potential to induce durable remissions in high-risk CLL without incurring excessive GVHD.