Use of L-asparaginase in acute lymphoblastic leukemia: recommendations of the Polish Adult Leukemia Group.
L-asparaginase is a hydrolase that catalyzes the conversion of L-asparagine--an endogenous amino acid necessary for the function of some neoplastic cells, such as lymphoblasts. In most human cells deficiency of L-asparagine can be compensated by alternative synthesis pathway through which L-asparagine is produced from aspartic acid and glutamine by asparagine synthethase. Depletion of L-asparagine from plasma by L-asparaginase results in inhibition of RNA and DNA synthesis with the subsequent blastic cell apoptosis. Owing to the unique anti-cancer mechanism of action, L-asparaginase has been introduced to the multi drug chemotherapy in children and adults with acute lymphoblastic leukemia, which has contributed to significant improvement of therapy outcomes and to achieve complete remission in about 90% of patients. Notwithstanding its high therapeutic efficacy, L-asparaginase can increase the risk of thrombosis. Inhibition of protein synthesis causes most complications observed during treatment with a native and pegylated form of L-asparaginase, including impaired functions of liver, kidneys or central nervous system. Thrombotic events occur as a result of inhibited synthesis of anticoagulant proteins (mainly antithrombin). Coagulopathy has been observed in 1.1-4% of patients treated with the pegylated L-asparaginase and in 2.1-15% of those receiving its native form. In this paper approaches to optimize the therapy with L-asparaginase have been discussed.
Piatkowska-Jakubas
Beata
B
Department of Hematology, Jagiellonian University, Medical College, Kraków, Poland. bjakubas@wp.pl
Krawczyk-Kuliś
Małgorzata
M
Giebel
Sebastian
S
Adamczyk-Cioch
Maria
M
Czyz
Anna
A
Lech Marańda
Ewa
E
Paluszewska
Monika
M
Pałynyczko
Grazyna
G
Piszcz
Jarosław
J
Hołowiecki
Jerzy
J
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001215:Asparaginase / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D017408:Guidelines as Topic; D006801:Humans; D011044:Poland; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012074:Remission Induction; D013927:Thrombosis / Q000139:chemically induced
D000970:Antineoplastic Agents; D001215:Asparaginase