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Despite recent advances, multiple myeloma remains an incurable disease. Induction therapy followed by autologous transplantation has become the standard of care. The idea of maintenance therapy in multiple myeloma is not new. Starting with chemotherapy in 1975, to interferon in 1998, to novel agents recently, a multitude of agents have been explored in patients with multiple myeloma. In spite of the novel agents, multiple myeloma continues to be an incurable disease with the progression-free survival after autologous transplant rarely exceeding 3 years. The goal of using maintenance therapy has been to improve the outcomes following autologous transplantation by increasing the progression-free survival, deepening remissions and perhaps increasing overall survival. It has been shown that patients with a stringent complete response (CR) have a better outcome [Kapoor et al. 2013]. It is becoming increasingly common to check minimal residual disease (MRD) as a means of assessing depth of response. It has also been shown that patients with no MRD have not only a better progression-free survival but also a better overall survival compared with patients who are MRD positive. This makes it even more important to find agents for maintenance therapy, which can further deepen and maintain responses. Here, we present a comprehensive review of the agents studied as maintenance for multiple myeloma and their efficacy, both in terms of overall survival, progression-free survival and toxicity.
Outcomes after allogeneic stem-cell transplantion (AHSCT) are influenced by both disease and patient related factors. Here we developed a novel prognostic model, Hematopoietic Cell Transplant-Composite Risk (HCT-CR), by combining the refined disease risk index (DRI-R) and hematopoietic stem-cell transplant comorbidity/age index (HCT-CI/Age) to predict post-transplant survival for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The analysis included 942 AML/MDS patients treated with AHSCT. Patients were stratified into 4 HCT-CR risk groups: Low-risk-Patients with low/intermediate DRI-R and HCT-CI/Age =3 (N=272); Intermediate-risk-Patients with low/intermediate DRI-R and HCT-CI/Age >3 (N=168); High-risk-Patients with high/very high DRI-R and HCT-CI/Age =3 (N=284); and Very high-risk-Patients with high/very high DRI-R and HCT-CI/Age >3 (N=184). Compared with low-risk group, intermediate, high and very high-risk group had significantly increased risk of death [adjusted HR of 1.37 (P0.04), 2.08 (P<0.001) and 2.92 (P<0.001), respectively]. The concordance test showed that the HCT-CR model provided better discriminative capacity for OS prediction compared with all prior models independently, including cytogenetic risk group, DRI-R and HCT-CI/Age model (C-indices 0.62, 0.55, 0.60 and 0.54, respectively) (P<0.001). In conclusion, combining disease and patient-related factors provides better survival stratification for patients with AML/MDS receiving AHSCT.
Background Ibrutinib, a Bruton's tyrosine kinase inhibitor has reformed the treatment of various B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Although generally well tolerated, here we describe our institutional experience of unique adverse effects encountered with the use of ibrutinib in patients with B-cell lymphomas. Methods This is a retrospective observational study done at a tertiary care facility, to evaluate adverse events in patients with B-cell malignancies on treatment with ibrutinib between 2014 and 2018. Further details including type of malignancy, cytogenetics, interventions for treatment of the side effect, and outcomes were obtained through electronic health record. Case series We found 10 patients with unique adverse events related to ibrutinib. Among those, six had chronic lymphocytic leukemia, two had Waldenstrom's macroglobulinemia, and two had mantle cell lymphoma. The events included palindromic rheumatoid arthritis, diffuse spongiotic dermatitis, bullous pemphigoid, recurrent hemorrhagic stroke, peripheral neuropathy, recurrent paronychia, intramedullary fibrosis, recurrent joint pains, pulmonary aspergillosis, dyspnea with exacerbation of atrial fibrillation, and resolution of autoimmune hemolytic anemia. Conclusion Our case series illustrates the wide variety of unique events recognized in patients treated with ibrutinib, some of which required cessation and most had dose reduction of the treatment. Thus, stressing the importance of early identification and intervention for the events to avoid worsening of toxicity and inability to continue treatment in such patients.
Background and Purpose— Industry payments to physicians raise concerns regarding conflicts of interest that could impact patient care. We explored nonresearch and nonownership payments from industry to vascular neurologists to identify trends in compensation. Methods— Using Centers for Medicare and Medicaid Services and American Board of Psychiatry and Neurology data, we explored financial relationships between industry and US vascular neurologists from 2013 to 2018. We analyzed payment characteristics, including payment categories, payment distribution among physicians, regional trends, and biomedical manufacturers. Furthermore, we analyzed the top 1% (by compensation) of vascular neurologists with detailed payment categories, their position, and their contribution to stroke guidelines. Results— The number of board certified vascular neurologist increased from 1169 in 2013 to 1746 in 2018. The total payments to vascular neurologist increased from $99 749 in 2013 to $1 032 302 in 2018. During the study period, 16% to 17% of vascular neurologists received industry payments. Total payments from industry and mean physician payments increased yearly over this period, with consulting fee (31.1%) and compensation for services other than consulting (30.7%) being the highest paid categories. The top 10 manufacturers made the majority of the payments, and the top 10 products changed from drug or biological products to devices. Physicians from south region of the United States received the highest total payment (38.72%), which steadily increased. Payments to top 1% vascular neurologists increased from 64% to 79% over the period as payments became less evenly distributed. Among the top 1%, 42% specialized in neuro intervention, 11% contributed to American Heart Association/American Stroke Association guidelines, and around 75% were key leaders in the field. Conclusions— A small proportion of US vascular neurologists consistently received the majority of industry payments, the value of which grew over the study period. Only 11% of the top 1% receiving industry payments have authored American Heart Association/American Stroke Association guidelines, but ≈75% seem to be key leaders in the field. Whether this influences clinical practice and behavior requires further investigation.
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