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l-Asparagine depletion levels and l-asparaginase activity in plasma of children with acute lymphoblastic leukemia under asparaginase treatment

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Abstract

Purpose

To determine the minimum levels of l-asparaginase (ASNase) activity necessary to maintain l-asparagine (Asn) depletion under ASNase treatment in acute lymphoblastic leukemia (ALL).

Methods

We measured ASNase activity using an enzyme coupling method with a limit of detection of 2 U/l and examined the relationship between ASNase activity and Asn levels in blood samples from 14 children with ALL.

Results

In all but one patient showing high ASNase antibody titers, minimum ASNase activity to maintain Asn depletion levels below the limit of detection (40 ng/ml) ranged from 6 to 180 U/l with a median value of 16 U/l. In 11 patients, the enzyme activity corresponding to minimum detectable Asn levels ranged from 2 to 32 U/l with a median value of 6.5 U/l. Patients with an ASNase activity of 2 U/l or an undetectable activity (<2 U/l) had nearly normal Asn levels: 4140±1161 ng/ml at 2 U/l and 7235±3107 ng/ml at <2 U/l (mean±SD). Statistical analysis showed that ASNase activity in the range of 2–32 U/l was inversely correlated with Asn levels (r=−0.803, P=0.001).

Conclusion

These results show that Asn levels are strongly correlated with plasma ASNase activity even at low enzyme activities (<50 U/l) and that this sensitive ASNase assay can be used to estimate plasma Asn depletion levels.

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Abbreviations

ALL:

Acute lymphoblastic leukemia

Asn:

Asparagine

ASNase:

Asparaginase

SSA:

Sulfosalicylic acid

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Authors and Affiliations

  1. Japanese Children’s Cancer and Leukemia Study Group (JCCLSG) Central Office, Department of Pediatrics, Faculty of Medicine, Aichi Medical University, 480-1195, Aichi, Japan

    Masahito Tsurusawa, Motoaki Chin, Asayuki Iwai, Keiko Nomura, Hideaki Maeba, Takashi Taga, Takeshi Higa, Tomoko Kuno, Toshinori Hori & Akiko Muto

  2. Pharmaceutical Research Institute Branch Office, Kyowa Hakko Kogyo Co. Ltd.,, 411-8731, Shizuoka, Japan

    Miyo Yamagata

Authors
  1. Masahito Tsurusawa
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  2. Motoaki Chin
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  3. Asayuki Iwai
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  4. Keiko Nomura
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  5. Hideaki Maeba
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  6. Takashi Taga
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  7. Takeshi Higa
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  8. Tomoko Kuno
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  9. Toshinori Hori
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  10. Akiko Muto
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  11. Miyo Yamagata
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Correspondence to Masahito Tsurusawa.

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Tsurusawa, M., Chin, M., Iwai, A. et al. l-Asparagine depletion levels and l-asparaginase activity in plasma of children with acute lymphoblastic leukemia under asparaginase treatment. Cancer Chemother Pharmacol 53, 204–208 (2004). https://doi.org/10.1007/s00280-003-0734-5

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  • DOI: https://doi.org/10.1007/s00280-003-0734-5

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