Purpose Lenalidomide is an oral immunomodulatory drug with multiple effects on the immune system and tumor cell microenvironment leading to inhibition of malignant cell growth. Based on encouraging reports of lenalidomide in relapsed and refractory chronic lymphocytic leukemia (CLL), we investigated the first-line use of single-agent lenalidomide in CLL. Patients and Methods Using a starting dose of lenalidomide 10 mg/d for 21 days of a 28-day cycle and weekly 5-mg dose escalations to a target of 25 mg, we encountered severe toxicities (tumor lysis, fatal sepsis) in the first two patients enrolled. The study was halted and the protocol amended to a more conservative regimen: starting dose of lenalidomide 2.5 mg with monthly escalations to a target dose of 10 mg, and extended tumor lysis prophylaxis and monitoring. Gene expression profiles from patient samples before and after 7 days of lenalidomide were performed. Results Twenty-five patients were enrolled on the amended protocol. No further tumor lysis events were reported. Tumor flare was common (88%) but mild. Grade 3 to 4 neutropenia occurred in 72% of patients, with only five episodes of febrile neutropenia. The overall response rate was 56% (no complete responses). Although rapid peripheral lymphocyte reductions were observed, rebound lymphocytoses during the week off-therapy were common. Lenalidomide-induced molecular changes enriched for cytoskeletal and immune-related genes were identified. Conclusion Lenalidomide is clinically active as first-line CLL therapy and is well-tolerated if a conservative approach with slow dose escalation is used. A lenalidomide-induced molecular signature provides insights into its immunomodulatory mechanisms of action in CLL.
Summary:The purpose of this study was to evaluate the estimated incidence of secondary malignancies post-allogeneic bone marrow transplantation (BMT) in a cohort of adult patients previously reported now with an additional 8.5 years of follow-up. A cohort of 557 patients older than age 16 years underwent allogeneic BMT between June 1970 and November 1993. Histologic reports confirmed the diagnosis of a secondary malignancy. Multivariate Cox proportional hazards method was utilized to investigate predictors for the development of secondary malignancies. In all, 31 patients in this cohort developed a secondary malignancy a median of 6.79 years after their transplant. The estimated cumulative incidence rate of secondary malignancy was 4.2% at 10 years post transplant. When compared to the general population, the estimated observed/expected ratio of new cancer diagnoses was 5.13. On multivariate analysis, older age at the time of transplant was the only significant predictor for development of secondary cancer (P ¼ 0.01). The most common malignancies observed were nonmelanomatous skin cancers and squamous cell cancers of the buccal cavity. The risk of developing a secondary malignancy after allogeneic BMT is significant, particularly in older patients. Long-term survivors of transplant require regular monitoring for early signs of cancer, particularly of the skin and oral cavity. Bone Marrow Transplantation (2005) 35, 51-55.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.