Prevention and management of asparaginase/pegasparaginase-associated toxicities in adults and older adolescents: recommendations of an expert panel.
ABSTRACT The rapidly increasing use of pegasparaginase (pegASNase) in adults, after a half century of use of asparaginase (ASNase) in children, has prompted a need for guidelines in the management and prevention of toxicities of asparagine depletion in adults. Accordingly, an initial set of recommendations are provided herein. Major advantages of pegASNase are its 2-3-week duration of action, in contrast to less than 3 days with native ASNase, and the flexibility of intravenous or intramuscular administration of pegASNase and associated patient and physician convenience. The most frequent toxicities of both types of ASNase are hepatic and pancreatic, with pancreatitis being the most serious. Other toxicities are hypersensitivity reactions, thrombosis, nausea/vomiting, and fatigue. Whether or not the replacement of one dose of pegASNase for 6-9 doses of native ASNase can be achieved in adults with similar efficacy and acceptable toxicities to those achieved in children remains to be established.
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ABSTRACT: To evaluate the feasibility of Pegaspargase instead of L-asparaginase to treat children with advanced-stage lymphoblastic lymphoma (LBL) on the Berlin-Frankfurt-Munster (BFM)-95 protocol. Fifty-four newly diagnosed patients with stage III or IV LBL and without any treatment were enrolled in this study. Pegaspargase took place of L-asparaginase in BFM-95. The complications and treatment responses of patients treated on the BFM-95 protocol and modified BFM-95 protocol were then evaluated respectively. Findings : For LBL patients treated with BFM-95 protocol or modified BFM-95 protocol, the complete response, event-free survival, overall survival were similar. Stage 4 myelosuppression was the most common complication in both groups. Besides that, among 31 patients receiving modified BFM-95 protocol, coagulation defects were the most common complication. In contrast, anaphylactic reaction was the most common complication in the other 23 patients receiving BFM-95 protocol. Modified BFM-95 protocol is available to children with advanced-stage LBL with an equal outcome and enhances its compliance and decreases the incidence of anaphylactic reaction, compared to BFM-95 protocol. Coagulation defects are the major complication and tolerable in modified one.Iranian Journal of Pediatrics 02/2014; 24(1):75-80. · 0.34 Impact Factor
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ABSTRACT: In the last two decades great improvements have been made in the treatment of childhood acute lymphoblastic leukemia, with 5-year overall survival rates currently approaching almost 90%. In comparison, results reported in adolescents and young adults (AYAs) are relatively poor. In adults, results have improved, but are still lagging behind those obtained in children. Possible reasons for this different pattern of results include an increased incidence of unfavorable and a decreased incidence of favorable cytogenetic abnormalities in AYAs compared with children. Furthermore, in AYAs less intensive treatments (especially lower cumulative doses of drugs such as asparaginase, corticosteroids and methotrexate) and longer gaps between courses of chemotherapy are planned compared to those in children. However, although favorable results obtained in AYAs receiving pediatric protocols have been consistently reported in several international collaborative trials, physicians must also be aware of the specific toxicity pattern associated with increased success in AYAs, since an excess of toxicity may compromise overall treatment schedule intensity. Cooperative efforts between pediatric and adult hematologists in designing specific protocols for AYAs are warranted.08/2014; 6(3):5554. DOI:10.4081/hr.2014.5554
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ABSTRACT: Pediatric acute lymphoblastic leukemia (ALL) cure rates have markedly improved over the past years to approximately 85%, but remain at 40%-50% in adults. Redefining current adult chemotherapy regimens is likely to improve the natural course of the disease, but new agents are needed. Immunotherapy approaches for pre-B ALL are in the forefront of research on novel agents; in particular, advances are being made in manipulating autologous T cells either by infusion of a bifunctional antibody (eg, blinatumomab) or by ex vivo genetic modification of chimeric antigen receptors (CARs). The natural course of Philadelphia positive ALL has already improved by targeting ABL/BCR1. Other mutated genes are being discovered and novel small molecules that target their products are being studied in clinical trials. Finally, ALL is a heterogeneous disease and novel agents are likely to impact the natural course of smaller populations of biologically defined ALL subtypes.Bailliè re s Best Practice and Research in Clinical Haematology 09/2014; 27(3-4). DOI:10.1016/j.beha.2014.10.006 · 2.55 Impact Factor