Calaspargase pegol, sold under the brand name Asparlas, is a medication for the treatment of acute lymphoblastic leukemia (ALL). It is approved in the United States as a component of a multi-agent chemotherapeutic regimen for ALL in pediatric and young adult patients aged one month to 21 years.Calaspargase pegol is an engineered protein consisting of the E. coli-derived enzyme L-asparaginase II conjugated with succinimidyl carbonate monomethoxypolyethylene glycol (pegol). The L-asparaginase portion hydrolyzes L-asparagine to L-aspartic acid depriving the tumor cell of the L-asparagine it needs for survival. The conjugation with the pegol group increases the half-life of the drug making it longer acting. The most common (incidence ≥ 10%) grade ≥ 3 adverse reactions are elevated transaminase, increased bilirubin, pancreatitis, and abnormal clotting studies. History
In December 2018, calaspargase pegol-mknl was approved in the United States as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) in pediatric and young adult patients age one month to 21 years.Approval was based on a demonstration of the achievement and maintenance of nadir serum asparaginase activity above the level of 0.1 U/mL when using calaspargase pegol-mknl, 2500 U/m2 intravenously, every three weeks. The pharmacokinetics of calaspargase pegol-mknl were studied when administered in combination with multiagent chemotherapy in 124 subjects with B-cell lineage ALL.The FDA approved calaspargase pegol-mknl based on evidence primarily from two clinical trials (Trial 1/NCT01574274 and Trial 2/AALL07P4) of 237 subjects with acute lymphoblastic leukemia (ALL).
Occupational asthma is new onset asthma or the recurrence of previously quiescent asthma directly caused by exposure to an agent at workplace. It is an occupational lung disease and a type of work-related asthma. Agents that can induce occupational asthma can be grouped into sensitizers and irritants.Sensitizer-induced occupational asthma is an immunologic form of asthma which occurs due to inhalation of specific substances (i.e., high-molecular-weight proteins from plants and animal origins, or low-molecular-weight agents that include chemicals, metals and wood dusts) and occurs after a latency period of several weeks to years.Irritant-induced (occupational) asthma is a non-immunologic form of asthma that results from a single or multiple high dose exposure to irritant products. It is usually develops early after exposure; however can also develop insidiously over a few months after a massive exposure to a complex mixture of alkaline dust and combustion products, as shown in the World Trade Center disaster. Unlike those with sensitizer-induced occupational asthma, subjects with irritant-induced occupational asthma do not develop work-related asthma symptoms after re-exposure to low concentrations of the irritant that initiated the symptoms. Reactive airways dysfunction syndrome (RADS) is a severe form of irritant induced asthma where respiratory symptoms usually develop in the minutes or hours after a single accidental inhalation of a high concentration of irritant gas, aerosol, vapor, or smoke.Another type of work-related asthma is work-exacerbated asthma (WEA) which is asthma worsened by workplace conditions but not caused by it.