Prior to this approval, intravenous (IV) artesunate was only available through the Expanded Access program of the U.S. Food and Drug Administration (FDA), which allowed the Centers for Disease Control and Prevention (CDC) to provide IV artesunate to people in the U.S. with severe malaria and to people with uncomplicated malaria who are unable to take oral medications under an investigational new drug (IND) protocol. There has been no FDA-approved drug for treatment of severe malaria in the United States since the marketing of quinidine was discontinued by the manufacturer in March 2019.The safety and efficacy of IV artesunate for the treatment of severe malaria was primarily evaluated in a randomized controlled trial in Asia (Trial 1) and a supportive published randomized controlled trial in Africa (Trial 2). Trial 1 was conducted at 10 sites in Myanmar, Bangladesh, India, and Indonesia.Trial 1 enrolled 1,461 participants who received either IV artesunate or the comparator drug quinine and included 202 pediatric participants younger than 15 years. Trial 2 included 5,425 randomized pediatric participants younger than 15 years of age with severe malaria who were treated with artesunate or quinine. In both trials, the number of participants treated with artesunate who died in the hospital was significantly lower than the number who died in the control group treated with quinine. Trial 2 was conducted during 2005–2010 in nine African countries.
Due to the similarities among lymphoproliferative disorders, it is often difficult to diagnose patients. Immunophenotyping helps distinguish B-PLL from similar diseases, one of its key identifiers is the absence in expression of the surface antigens CD10, CD11c, CD25, CD103 and cyclin D1 – an important regulator of cell-cycle progression.A case has been described as CD20+, CD22+, and CD5-.It can also be CD5+.Another case was described as CD45+, CD19+, CD20+, CD5+, HLA-DR+, CD10-, CD23+/-, CD38+ and FMC7-. Cytogenetics
B-PLL is rare, consequently few genetic studies have focused on this disease. As a result, the associated genetic lesions underlying B-PLL are largely unknown. Chromosomal Mutations
The most commonly reported abnormalities have occurred at chromosome 14, specifically in a region of the chromosome called band q23 (14q23). Translocations to this location lead to overexpression of the cyclin D1 gene which has been linked to both the development and progression of a number of cancers. Other chromosomal abnormalities have been reported on 6q21, 11q23, 12p12, 13q14 and 17p.It can involve deletions from chromosome 11 and chromosome 13. TP53 Gene
Among the documented studies, mutations to the TP53 gene have occurred in 75% of all cases of B-PLL. This is the highest incidence among all sub-types of B-cell malignancies. Mutations to this gene have also been documented in other hematologic malignancies.TP53 is an important transcriptional activator of genes involved in the regulation of the G1 checkpoint of the cell cycle as well as certain genes responsible for programmed-cell death (apoptosis).