Changes in Fibrinogen and Total Protein/Albumin Levels During Induction Chemotherapy in Children with Acute Lymphoblastic Leukemia Akut Lenfoblastik Lösemili Çocuklarda İndüksiyon Kemoterapisi Süresince Fibrinojen ve Total Protein/ Albumin Düzeyinde Meydana Gelen Değişiklikler

Yıl 2017, Cilt: 39 Sayı: 2, 45 - 50, 26.05.2017

Zeynep Canan Özdemir , Ayşe Bozkurt Turhan Özcan Bör

https://doi.org/10.20515/otd.316147

Öz

Abstract: L-Asparaginase is an important drug for treatment of
childhood acute lymphoblastic leukemia (ALL). The impairment of protein
synthesis due to depletion of asparagine by asparaginase leads to decreases in
albumin and deterioration in hemostasis tests. 
The aims of the present study were to conduct a retrospective evaluation
of levels of fibrinogen, total protein/albumin during induction chemotherapy in
children with ALL treating according to the BFM 2009 protocol.For this purpose,
the laboratory data of 45 pediatric ALL patients in the induction chemotherapy
between August 2011 and March 2016 were retrospectively evaluated. This study
was approved institutional review board of Eskişehir Osmangazi University
Faculty of Medicine (Ethics approval No: 80558721/105). The median fibrinogen
level on day 12 was already reduced by 62% compared to the before treatment
values, but this difference was not statistically significant (p>0.05).  After 15 days of therapy, the level of
fibrinogen decreased to 27%, total protein decreased to 89%, albumin decreased
to 92% of the inital value (p<0.001,p<0.01,p<0.05, respectively). The
lowest fibrinogen and total protein/albumin levels were observed on the 21st
and 27th days of chemotherapy. Thrombotic complication developed in three
children (9.3%). The results showed that the levels of fibrinogen and total
protein/albumin were significantly reduced during the induction chemotherapy.

Keywords: induction chemotherapy, L-asparaginase,
children, fibrinogen, protein, albumin.

Keywords: induction chemotherapy, L-asparaginase,
children, fibrinogen, protein, albumin

Öz: Asparaginaz, çocukluk çağı akut lenfoblastik
lösemi tedavisinde kullanılan önemli bir ilaçtır.Asparaginaz’ın asparagin
tükenmesine bağlı olarak yol açtığı protein sentezindeki bozulma albüminde
azalmaya ve hemostaz testlerinde bozulmaya neden olur. Bu çalışmanın amacı, BFM
2009 protokolüne göre tedavi alan akut lenfoblastik lösemili çocuklarda
indüksiyon kemoterapisi sırasında fibrinojen, total protein/albumin
düzeylerinin retrospektif olarak değerlendirilmesidir. Bu amaçla, Ağustos 2011
ile Mart 2016 tarihleri arasında indüksiyon kemoterapisi alan 45 hastasının
laboratuvar parametreleri geriye dönük olarak incelendi. Çalışma için Eskişehir
Osmangazi Üniversitesi Klinik Araştırmalar Etik Kurulu’ndan onam alındı (Etik
kurul onam numarası: 80558721/105). Onikinci günde medyan fibrinojen düzeyi
tedavi başlangıcına göre %62 oranında azalmıştı. Ancak bu farklılık
istatistiksel açıdan anlamlı değildi (p>0.05). Tedavi sonrası 15. günde
medyan fibrinojen düzeyi  tedavi öncesi
değerin%27’sine, total protein % 89’una, albumin %92’sine düşmüştü
(p<0,001,p<0,01,p<0,05, sırasıyla). Fibrinojen ve total
protein/albumin düzeyleri 21. ve 27. günlerde en düşük düzeyde idi.  Üç hastada tromboembolik komplikasyon gelişti
(%9,3). Çalışmanın sonuçları, indüksiyon kemoterapisi süresinde fibrinojen, kan
total protein/albumin düzeylerinin önemli ölçüde düştüğünü gösterdi.

Anahtar kelimeler: indüksiyon kemoterapisi,
L-Asparaginaz, çocuk, fibrinojen, protein, albümin

Anahtar Kelimeler

induction chemotherapy, L-asparaginase, children, fibrinogen, protein

Kaynakça

• 1. Clavell, L., Gelber, R., Cohen, H., et al. (1986) Four-agent induction and intensive asparaginase therapy for treatment of childhood acute lymphoblastic leukemia. N Engl J Med, 315(11), 657-63.
• 2. Duval, M., Suciu, S., Ferster, A., et al. (2002) Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organization for Research and Treatment of Cancer-Children’s Leukemia Group phase 3 trial. Blood, 99(8), 2734-9.
• 3. Mitchell, L.G., Halton, J.M., Vegh, P.A., et al.(1994) Effect of disease and chemotherapy on hemostasis in children with acute lymphoid leukemia. Am J Pediatr Hematol Oncol, 16(2), 120-6.
• 4. De Stefano, V., Za, T., Ciminello, A., Betti, S., Rossi, E. (2015) Haemostatic alterations induced by treatment with asparaginases and clinical consequences.Thromb Haemost, 113(2), 247-61.
• 5. Appel, I.M., Hop, W.C., van Kessel-Bakvis, C., Stigter, R., Pieters, R. (2008) L-Asparaginase and the effect of age on coagulation and fibrinolysis in childhood acute lymphoblastic leukemia. Thromb Haemost, 100(2), 330-7.
• 6. Rozen, L., Noubouossie, D., Dedeken, L., et al. (2017) Different profile of thrombin generation in children with acute lymphoblastic leukemia treated with native or pegylated asparaginase: A cohort study. Pediatr Blood Cancer, 64(2), 294-01.
• 7. Caruso, V., Iacoviello, L., Di Castelnuovo, A., et al. (2006) Thrombotic complications in childhood acute lymphoblastic leukemia: A meta-analysis of 17 prospective studies comprising 1752 pediatricpatients. Blood, 108,2216–22.
• 8. Payne, J.H., Vora, A.J. (2007) Thrombosis and acute lymphoblastic leukaemia. Br J Haematol, 138, 430–45.
• 9. Sutor, A.H., Niemeyer, C., Sauter. S., et al. (1992) Changes in blood coagulation in treatment with ALL-BFM-90 and NHL-BFM-90 protocols. Klin Padiatr, 204(4), 264-73.
• 10. Korte, W., Feldges, A., Baumgartner, C., Ullmann, S., Niederer, V., Schmid, L. (1994) Increased thrombin generation during fibrinogen and platelet recovery as an explanation for hypercoagulability in children with L-asparaginase therapy for ALL or NHL: a preliminary report. Klin Padiatr, 206, 331–33.
• 11. Hunault- Berger, M., Chevallier, P., Delain, M., et al. (2008) Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation
• 12. therapy and clinical outcome: the CAPELAL study. Haematologica, 93(10), 1488-94.
• 13. Giordano, P., Molinari, A.C., Del Vecchio, G.C., et al. (2010) Prospective study of hemostatic alterations in children with acute lymphoblastic leukemia. Am J Hematol, 85(5), 325-30.
• 14. Attarbaschi, A., Mann, G., Kronberger, M., Witt, V., Gadner, H., Dworzak, M.(2003) Effects of dose-reduced Medac L-asparaginase on coagulation in trial ALL-BFM 2000. Klin Padiatr, 215(6), 321-6.