L-Asparaginase in Acute Childhood Leukemia: Clinical Outcomes and Toxicity Assessment

Year 1973, Volume: 26 Issue: 5-6, 1165 - 1180, 31.12.1973

Ülkü Topuz

Abstract

Bu çalışma, Ankara Üniversitesi Tıp Fakültesi’nde akut lenfoblastik lösemi tanısı konmuş sekiz çocuk hastada, E. coli kaynaklı L-Asparaginaz ("Crasnitin") kullanımının klinik etkilerini ve yan etkilerini incelemektedir. Hastalar daha önce direnç gelişmiş farklı kemoterapi protokolleriyle tedavi edilmişti. L-Asparaginaz tedavisiyle 3 hastada 4–7 haftalık sürede tam remisyon elde edilmiş ve bu remisyon 15–27 hafta sürmüştür. Bazı hastalarda yalnızca parsiyel yanıt alınmış, terminal dönemdeki hastalarda ise sonuçlar yetersiz kalmıştır. İlaç çeşitli toksik etkilere yol açmıştır: iştahsızlık, bulantı, hipersensitivite reaksiyonları, karaciğer enzim bozuklukları, koagülasyon defektleri, lökopeni, hipokalsemi ve santral sinir sistemi belirtileri gibi. Tüm bu bulgular, L-Asparaginaz’ın özellikle dirençli vakalarda etkili bir seçenek olabileceğini, ancak toksisite açısından dikkatle izlenmesi gerektiğini göstermektedir.

Keywords

çocuk , lösemi , toksik

Akut Çocukluk Lösemisinde L-Asparaginaz: Klinik Bulgular ve Toksisite Değerlendirmesi

Abstract

This study evaluates the clinical effects and toxicity profile of E. coli-derived L-Asparaginase ("Crasnitin") in eight pediatric patients diagnosed with acute lymphoblastic leukemia at Ankara University Medical Faculty. All patients had previously received various chemotherapy regimens, with some developing resistance. L-Asparaginase induced complete remission in three cases within 4–7 weeks, lasting 15–27 weeks. Partial responses were observed in others, while results were poor in terminal cases. Multiple adverse effects were recorded, including gastrointestinal symptoms, hypersensitivity reactions, hepatic enzyme alterations, coagulation abnormalities, leukopenia, hypocalcemia, and central nervous system symptoms. The findings suggest that L-Asparaginase can be a potent therapeutic option in refractory leukemia cases but requires careful monitoring due to its diverse toxicity profile.

Keywords

çocuk , lösemi , toksik

References

• 1 - Kidd, I. G. : Regression of Transplanted Lymphomas Induced in Vivo by Means of Normal Guinea Pig Serum. J. Exp. Med. 98: 565, 1953.
• 2 - Burchenal, J. H., Karnofsky, D. A. : Clinical Evaluation of L-Asparaginase. Cancer. 25: 241, 1970.
• 3 - Broome, J. D. : L-Asparaginase Activity of Guinea Pig Serum and Its Anti-Lymphoma Effects. Nature. 191: 1114, 1961.
• 4 - Broome, J. D. : Mechanism of Tumor Inhibition by L-Asparaginase. J. Exp. Med. 127: 1055, 1968.
• 5 - Broome, J. D. : Development of Asparaginase Therapy. Clinical Excerpts (Bayer-Germany). 33: 876, 1971.
• 6 - Mashburn, L. T., Wriston, J. G. : Tumor Inhibitory Effect of L-Asparaginase from E. coli. Arch. Biochem. Biophys. 105: 450, 1964.
• 7 - Campbell, H. A. et al. : Separation and Anti-Tumor Activity of Two L-Asparaginases from E. coli. Biochemistry. 6: 721, 1967.
• 8 - Boyse, E. A. et al. : Suppression of Murine Leukemias by L-Asparaginase. J. Exp. Med. 125: 17, 1967.
• 9 - Cole, W. H. : Chemotherapy of Cancer. Henry Kimpton Pub., London, 1970, s. 82.
• 10 - Carter, R. L. et al. : L-Asparaginase Success Depends on Host Immune Response. Int. J. Cancer. 11: 345–357, 1973.
• 11 - Jaffe, N. et al. : Comparison of Daily and Twice Weekly Schedule of L-Asparaginase. Pediatrics. 49: 590, 1972.
• 12 - Jaffe, N. et al. : Favorable Remission Induction Rate with Twice Weekly Doses of L-Asparaginase. Cancer Research. 33: 1–4, 1973.
• 13 - Pratt, C. B. et al. : Daily vs Weekly L-Asparaginase in Childhood Leukemia. Pediatrics. 77: 474–483, 1970.
• 14 - Haskell, C. M. et al. : Therapeutic and Toxic Effects in Neoplastic Disease. N. Engl. J. Med. 281: 1028, 1969.
• 15 - Schmitt, C. G. : Problems in L-Asparaginase Therapy. Clinical Excerpts (Bayer-Germany). 33: 885, 1971.
• 16 - Clarkson, B. et al. : Clinical Use of E. Coli L-Asparaginase in Adults. Cancer. 25: 279–305, 1970.
• 17 - Oettgen, H. F. et al. : Toxicity of E. Coli L-Asparaginase in Humans. Cancer. 25: 253–278, 1970.
• 18 - Tallal, L. et al. : Treatment of Children with Acute Leukemia and Solid Tumors. Cancer. 25: 306–320, 1970.
• 19 - Zubrod, G. G. : Clinical Toxicities of L-Asparaginase. Pediatrics. 45: 555, 1970.
• 20 - Hill, J. M. : Further Clinical Experiences with L-Asparaginase. Clinical Excerpts (Bayer-Germany). 33: 892, 1971.
• 21 - Goldberg, A. I. et al. : Effect of Immunisation to L-Asparaginase on Its Activity. Cancer Research. 33: 256–261, 1973.
• 22 - McElwain, T. J., Hardisty, R. M. : Remission Induction with Cytosine Arabinoside and L-Asparaginase. Brit. Med. J. 4: 596–598, 1968.
• 23 - Astaldi, G. : Is L-Asparaginase an Antiblastik Agent? Hematologia. 6: 888, 1972.