Unacceptable Toxicity of Lenalidomide When Administered to CLL Patients at Higher Doses.

Abstract Lenalinomide is an immunomodulatory agent with activity in hematologic malignancies including multiple myeloma and myelodysplastic syndrome. Recent phase II studies have demonstrated that lenalidomide has significant activity in chronic lymphocytic leukemia (CLL). Patients included in this report including a single patient treated off study based on available data for cytoreduction for planned allogeneic stem cell transplantation. Three additional patients with relapsed CLL were enrolled on a IRB approved phase I study evaluating the optimal initial dose in CLL. All patients were treated at 25 mg/day for 21 days with a 7 day off period. Because of previous reports of tumor lysis syndrome and tumor flare during initiation of therapy, patients were initially monitored daily in the outpatient setting with physical examinations and laboratory evaluation. All patients received prophylactic corticosteroids consisting of dexamethasone 12 mg orally days 1–7 followed by 4 mg orally days 7–14 except patient #1, who received prednisone 20 mg daily. Patient specific histories include: Patient #1 had bulky lymphadenopathy and a WBC count of 197,000 at the time of initiation of therapy. On day 3 of therapy he omitted his steroid prophylaxis and rapidly developed a syndrome of worsening lymphocytosis, lymph node enlargement, acute renal failure with laboratory evidence of tumor lysis syndrome, and despite mechanical ventilation died of hypoxemic respiratory failure on day 10 of therapy. Patient #2 initially did well, however on day 25 of course 1 presented to an outside facility with gram negative sepsis in the setting of neutropenia. He recovered fully, however soon after this episode developed disease progression and was taken off study. Patient #3 was asymptomatic until day 8 of course 1, when he developed symptoms of tumor flare during steroid taper with severe abdominal and back pain, skin rash, and low grade fevers. His symptoms resolved with cessation of therapy. He subsequently underwent serial dose reductions but continued to develop signs and symptoms of tumor flare requiring steroid therapy and narcotic pain medication. Patient #4 initiated therapy at 25 mg/day and did well during his steroid taper, however on day 25 while off therapy presented for evaluation of shortness of breath and airway occlusion with recumbency. He was found to have dramatic enlargement of cervical and supraclavicular lymph nodes as well as new tonsillar hypertrophy obstructing his airway; tonsillectomy demonstrated CLL without transformation in the tonsillar tissues. He received steroids with improvement and lenalidomide was discontinued. Lenalidomide administered at 25 mg orally daily is associated with unacceptable toxicity due to myelosuppression, tumor lysis syndrome, and tumor flare. Tumor flare may be indistinguishable from disease progression and may not respond to withdrawal of therapy and steroid administration. Future studies should be designed to initiate therapy at a low dose with gradual dose escalation, with close monitoring for complications. Given the uncertainty of safe dose and schedule of lenalidomide, use of this therapy off an IRB approved study that includes close patient monitoring for tumor flare should not be considered.</jats:p

2021 roadmap on lithium sulfur batteries

Batteries that extend performance beyond the intrinsic limits of Li-ion batteries are among the most important developments required to continue the revolution promised by electrochemical devices. Of these next-generation batteries, lithium sulfur (Li–S) chemistry is among the most commercially mature, with cells offering a substantial increase in gravimetric energy density, reduced costs and improved safety prospects. However, there remain outstanding issues to advance the commercial prospects of the technology and benefit from the economies of scale felt by Li-ion cells, including improving both the rate performance and longevity of cells. To address these challenges, the Faraday Institution, the UK's independent institute for electrochemical energy storage science and technology, launched the Lithium Sulfur Technology Accelerator (LiSTAR) programme in October 2019. This Roadmap, authored by researchers and partners of the LiSTAR programme, is intended to highlight the outstanding issues that must be addressed and provide an insight into the pathways towards solving them adopted by the LiSTAR consortium. In compiling this Roadmap we hope to aid the development of the wider Li–S research community, providing a guide for academia, industry, government and funding agencies in this important and rapidly developing research space

2021 roadmap on lithium sulfur batteries

Abstract Batteries that extend performance beyond the intrinsic limits of Li-ion batteries are among the most important developments required to continue the revolution promised by electrochemical devices. Of these next-generation batteries, lithium sulfur (Li–S) chemistry is among the most commercially mature, with cells offering a substantial increase in gravimetric energy density, reduced costs and improved safety prospects. However, there remain outstanding issues to advance the commercial prospects of the technology and benefit from the economies of scale felt by Li-ion cells, including improving both the rate performance and longevity of cells. To address these challenges, the Faraday Institution, the UK’s independent institute for electrochemical energy storage science and technology, launched the Lithium Sulfur Technology Accelerator (LiSTAR) programme in October 2019. This Roadmap, authored by researchers and partners of the LiSTAR programme, is intended to highlight the outstanding issues that must be addressed and provide an insight into the pathways towards solving them adopted by the LiSTAR consortium. In compiling this Roadmap we hope to aid the development of the wider Li–S research community, providing a guide for academia, industry, government and funding agencies in this important and rapidly developing research space.</jats:p