CALGB 50202 demonstrates for the first time to our knowledge that dose-intensive consolidation for PCNSL is feasible in the multicenter setting and yields rates of PFS and OS at least comparable to those of regimens involving WBRT. On the basis of these encouraging results, an intergroup study has been activated comparing EA consolidation with myeloablative chemotherapy in this randomized trial in PCNSL, in which neither arm involves WBRT.
Hypercoagulability can result from a variety of inherited and, more commonly, acquired conditions. Testing for the underlying cause of thrombosis in a patient is complicated both by the number and variety of clinical conditions that can cause hypercoagulability as well as the many potential assay interferences. Using an algorithmic approach to hypercoagulability testing provides the ability to tailor assay selection to the clinical scenario. It also reduces the number of unnecessary tests performed, saving cost and time, and preventing potential false results. New oral anticoagulants are powerful tools for managing hypercoagulable patients; however, their use introduces new challenges in terms of test interpretation and therapeutic monitoring. The coagulation laboratory plays an essential role in testing for and treating hypercoagulable states. The input of laboratory professionals is necessary to guide appropriate testing and synthesize interpretation of results.
Mutations of spliceosome components are common in myeloid neoplasms. One of the affected genes, PRPF8, encodes the most evolutionarily conserved spliceosomal protein. We identified either recurrent somatic PRPF8 mutations or hemizygous deletions in 15/447 and 24/450 cases, respectively. 50% of PRPF8 mutant and del(17p) cases were found in AML and conveyed poor prognosis. PRPF8 defects correlated with increased myeloblasts and ring sideroblasts in cases without SF3B1 mutations. Knockdown of PRPF8 in K562 and CD34+ primary bone marrow cells increased proliferative capacity. Whole RNA deep sequencing of primary cells from patients with PRPF8 abnormalities demonstrated consistent missplicing defects. In yeast models, homologous mutations introduced into Prp8 abrogated a block experimentally produced in the second step of the RNA splicing process suggesting that the mutants have defects in proof-reading functions. In sum, the exploration of clinical and functional consequences suggests that PRPF8 is a novel leukemogenic gene in myeloid neoplasms with a distinct phenotype likely manifested through aberrant splicing.
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