Neurophysiological evidence of impaired attention and working memory in untreated hematologic cancer patients.

OBJECTIVE: Neuroimaging studies of hematologic cancer patients report altered activity in dorsal attention and central executive networks. To determine the consequences of these altered brain networks, we evaluated neurophysiological correlates of attention and working memory in hematologic cancer patients prior to initiating treatment. METHODS: Hematologic cancer patients (19-80 years) were excluded for premorbid cognitive impairment, prior non-hematologic cancer diagnosis, and prior chemotherapy. Attention was manipulated by presenting an irrelevant spatial cue prior to visual search displays. Working memory was manipulated by presenting irrelevant distractors within memory displays. Electroencephalogram was recorded during task performance. RESULTS: Patients (n = 28) and controls (n = 15) were balanced on age, gender, and education. Spatial cues evoked larger N2pc amplitudes, a correlate of spatial attention, in patients than controls (p < .05; Cohen's d > 0.7). Memory distractors evoked larger contralateral delay activity amplitudes, a correlate of working memory load, in patients (p = .028; Cohen's d = 1.1) but not controls (p = .64). CONCLUSIONS: Prior to initiating treatment, hematologic cancer patients demonstrated poor control over spatial attention and working memory, consistent with altered dorsal attention and central executive network activity. SIGNIFICANCE: Hematologic cancer patients may be at a higher risk for selecting, processing, and storing distracting information that would compete with more immediate goal-related behaviors.

Mutation of chromatin modifiers; an emerging hallmark of germinal center B-cell lymphomas.

Subtypes of non-Hodgkin's lymphomas align with different stages of B-cell development. Germinal center B-cell (GCB)-like diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Burkitt's lymphoma (BL) each share molecular similarities with normal GCB cells. Recent next-generation sequencing studies have gained insight into the genetic etiology of these malignancies and revealed a high frequency of mutations within genes encoding proteins that modifying chromatin. These include activating and inactivating mutations of genes that perform post-translational modification of histones and organize chromatin structure. Here, we discuss the function of histone acetyltransferases (CREBBP, EP300), histone methyltransferases (KDM2C/D, EZH2) and regulators of higher order chromatin structure (HIST1H1C/D/E, ARID1A and SMARCA4) that have been reported to be mutated in ⩾5% of DLBCL, FL or BL. Mutations of these genes are an emerging hallmark of lymphomas with GCB-cell origins, and likely represent the next generation of therapeutic targets for these malignancies.

Romiplostim for management of chemotherapy-induced thrombocytopenia.

PURPOSE: Chemotherapy-induced thrombocytopenia (CIT) can cause delay or reduction in subsequent courses of chemotherapy. Here, we report on a series of 20 patients who had protracted CIT and were treated with romiplostim, a thrombopoietin receptor agonist. PATIENTS AND METHODS: We performed a retrospective review of the use of romiplostim for dose-limiting CIT at Memorial Sloan-Kettering Cancer Center from 2010-2012. Romiplostim was initiated at 1-2 mcg/kg weekly, with dose escalation by 1 mcg/kg per week until recovery of platelets (≥ 100 × 10(9)/L). If patients resumed chemotherapy, weekly romiplostim was continued. RESULTS: Romiplostim improved platelet counts in all 20 patients. In 19 of 20 patients, platelet counts of ≥ 100 × 10(9)/L were achieved. The mean dose of romiplostim to achieve adequate platelet recovery was 2.9 mcg/kg (range 1.0-5.1). Sixteen patients achieved platelet recovery by 2 weeks. Fifteen patients resumed cytotoxic chemotherapy with continued romiplostim support and 14 tolerated at least two subsequent cycles of chemotherapy, on schedule, without recurrence of dose-limiting CIT. Sepsis prevented continued chemotherapy in one patient. No resistance to romiplostim was observed. Three deep vein thromboses (DVT) were observed; one of which was a recurrent DVT in a patient who had previously experienced a DVT and was off anticoagulation. Three DVTs within 20 patients is within the anticipated thrombosis rates of patients with active cancer on chemotherapy. CONCLUSION: Romiplostim resulted in improvement in platelet counts, allowing resumption of chemotherapy without recurrence of dose-limiting CIT. No treatment-related toxicity was observed, but this would need to be confirmed in a larger, prospective trial. Our series differs from prior studies in that we selected only those patients who had already demonstrated persistent thrombocytopenia, and we continued weekly romiplostim during chemotherapy. Romiplostim may be a safe and effective treatment for CIT.