TÜRKİYE’DEKİ KRONİK MİYELOİD LÖSEMİ HASTALARINDA KAN PARAMETRELERİNİN BCR/ABL1 P210 TESTİ ÜZERİNE ETKİLERİ

Year 2023, Volume: 6 Issue: 3, 367 - 372, 21.10.2023

Cem Karaosmanoğlu , Saliha Handan Yıldız , Müjgan Özdemir Erdoğan , Filiz Yavaşoğlu , Haktan Doğuş

https://doi.org/10.53446/actamednicomedia.1338837

Abstract

Amaç: Kronik miyeloid lösemi (KML), BCR/ABL1 füzyon geninden kaynaklanan en yaygın hematolojik malignitelerden biridir. KML'li hastalar genellikle bazofili ve nötrofili içeren lökositoz gösterirler. KML'nin doğrulanması genellikle BCR/ABL1 füzyonunun saptanmasına dayanır. KML şüphesi olan hastalarda BCR/ABL1 p210 testi için periferik kan (PK) diferansiyeli ve tam kan sayımının (TKS) etkisini araştırmayı amaçlıyoruz.
Metot: BCR/ABL1 p210 füzyonu için ilk kez test edilen hastaların retrospektif bir değerlendirmesini yaptık. Kliniğimiz veri tabanından 235 hastanın klinik ve laboratuvar bulgularını elde ettik. BCR/ABL1 p210 füzyonu, kantitatif Gerçek Zamanlı Polimeraz Zincir Reaksiyonu (RT-qPCR) ile tespit edilmiştir. Sürekli verilerin karşılaştırılması için t-testi veya Mann-Whitney U testleri uyguladık. Her parametre için alıcı çalışma karakteristiğini (ROC eğrileri) çizdik ve ROC eğrisi altındaki alanı (AUC) hesapladık.
Bulgular: 235 hastanın 25'ine (%10.6) yeni KML tanısı kondu. KML hastalarında, diferansiyel ile önemli ölçüde artmış beyaz kan hücresi sayısı (WBC) vardı. Mutlak bazofil sayısı, 0,3 × 103/uL'lik bir kesme değerine sahip olan 0,829'luk ROC eğrisi (AUC) değerinin altındaki en yüksek alanı gösterdi. KML vakalarının %76,00'ında mutlak bazofil sayısı ≥0,3 × 103/uL iken, KML olmayan vakaların %95,24'ünde mutlak bazofil sayısı <0,3 × 103/uL idi.
Sonuç: Sonuçlarımız, ≥0,3 × 103/uL mutlak bazofil sayısının BCR/ABL1 p210 test istemini iyileştirmeye ve sağlık hizmeti maliyetlerini düşürmeye yardımcı olabileceğini göstermektedir.

Keywords

KML, BCR/ABL1 füzyonu, RT-qPCR, TKS

IMPACT OF BLOOD PARAMETERS ON BCR/ABL1 P210 TESTING IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA IN TURKIYE

Abstract

Objective: Chronic myeloid leukemia (CML) is one of the most common hematological malignancies derived from the BCR/ABL1 fusion gene. Patients with CML generally manifest leukocytosis with basophilia and neutrophilia. The verification of CML is often based on the detection of BCR/ABL1 fusion. We aimed to investigate the impact of peripheral blood (PB) differential and complete blood count (CBC) on BCR/ABL1 p210 test ordering in patients with suspected CML.
Methods: We performed a retrospective assessment of patients tested for the first time for BCR/ABL1 p210 fusion. We obtained clinical and laboratory findings of 235 patients from the database of our clinic. BCR/ABL1 p210 fusion was detected by quantitative real-time polymerase chain reaction (RT-qPCR). We implemented t-tests or Mann–Whitney U tests for the comparison of continuous data. We plotted the receiver operating characteristic (ROC curves) and calculated the area under the ROC curve (AUC) for each parameter.
Results: Among 235 patients, 25 (%10.6) received a new diagnosis of CML. CML patients had significantly increased white blood cell count (WBC) with differential. Absolute basophil count showed the highest area under the ROC curve (AUC) value of 0.829, which had a cut-off value of 0.3 × 103/ µL. 76.00% of CML cases had an absolute basophil count of ≥0.3 × 103/µL, while 95.24% of the non-CML cases had an absolute basophil count of <0.3 × 103/µL.
Conclusions: Our results indicate that an absolute basophil count of ≥0.3 × 103/µL can help improve BCR/ABL1 p210 test ordering and reduce healthcare costs.

Keywords

CML, BCR/ABL1 fusion, RT-qPCR, CBC

References

• Rowley JD. New Consistent Chromosomal Abnormality in Chronic Myelogenous Leukaemia identified by Quinacrine Fluorescence and Giemsa Staining. Nature 1973;243:290–293. doi.org/10.1038/243290a0
• Quintás-Cardama A, Cortes J. Molecular biology of bcr-abl1–positive chronic myeloid leukemia. Blood 2009;113:1619–1630. doi.org/10.1182/blood-2008-03-144 790
• Chereda B, Melo JV. The biology and pathogenesis of chronic myeloid leukemia. In: Chereda B, Melo JV, In Chronic Myeloid Leukemia. 1st ed. Cham, Switzerland: Springer; 2016:17–39.
• Faderl S, Talpaz M, Estrov Z, O’Brien S, Kurzrock R, Kantarjian HM. The Biology of Chronic Myeloid Leukemia. N. Engl. J. Med. 1999;341:164–172. doi.org/10.1056/NEJM 199907153410306.
• Wylie AA, Schoepfer J, Jahnke W, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1. Nature 2017;543:733–737. doi.org/10.1038/nature21702
• Fava C, Rege-Cambrin G, Saglio G. The choice of first-line Chronic Myelogenous Leukemia treatment. Ann Hematol. 2015;94:123-131. doi.org/10.1007/s00277-015-2321-3
• Wong WJ, Pozdnyakova O. Myeloproliferative neoplasms: Diagnostic workup of the cythemic patient. Int J Lab Hematol. 2019;41:142-150. doi.org/10.1111/ijlh.13005
• Shanbehzadeh M, Afrash MR, Mirani N, Kazemi-Arpanahi H. Comparing machine learning algorithms to predict 5-year survival in patients with chronic myeloid leukemia. BMC Med Inform Decis Mak. 2022;22:236. doi.org/10.1186/ s12911-022-01980-w
• Clarke CJ, Holyoake, TL. Preclinical approaches in chronic myeloid leukemia: from cells to systems. Exp Hematol. 2017;47:13-23. doi.org/10.1016/j.exphem.2016.11.005
• Galli SJ, Metcalfe DD, Arber DA, Dvorak AM. In: Basophils and mast cells and their disorders. Williams Hematology. 8th ed. McGraw-Hill, New York, 2010:915-932
• Ogunleye F, Ibrahim M, Allen E, et al. BCR-ABL testing by polymerase chain reaction in patients with neutrophilia: the William Beaumont hospital experience and the case for rational laboratory test requests. J Oncol Pract. 2016;12:1001-e1005. doi.org/10.1200/JOP.2016.014449
• Masuda A, Jona M, Satoh Y, et al. The criteria to suspect chronic myeloid leukemia using absolute basophil counts in peripheral blood. Int J Hematol. 2015;101:626-628. doi.org/10.1007/s12185-015-1777-1
• Ogasawara A, Matsushita H, Tanaka Y, et al. A simple screening method for the diagnosis of chronic myeloid leukemia using the parameters of a complete blood count and differentials. Clin Chim Acta. 2019;489:249-253. doi.org/10.1016/j.cca.2018.08.038
• Esen E, Keceli MC. Economic Growth and Health Expenditure Analysis for Turkey: Evidence from Time Series. Journal of the Knowledge Economy 2022;13:1786–1800. doi.org/10.1007/s13132-021-00789-8
• Hochhaus A, O’Brien SG, Guilhot F, et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 2009;23:1054-61. doi.org/10.1038/leu.2009.38
• Denburg JA, Wilson WE, Bienenstock J. Basophil production in myeloproliferative disorders: increases during acute blastic trans formation of chronic myeloid leukemia. Blood 1982;60:113-120. doi.org/10.1182/blood.V60.1.113.113
• Denburg JA, Browman G. Prognostic implications of basophil differentiation in chronic myeloid leukemia. Am J Hematol. 1988;27:110-114. doi.org/10.1002/ajh.2830270 208
• Hasford J, Baccarani M, Hoffmann V, et al. Predicting complete cytogenetic response and subsequent progression free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood 2011;118:686-692. doi.org/10.1182/blood-2010-12-319038
• de Paulis A, Prevete N, Fiorentino I, et al. Expression and functions of the vascular endothelial growth factors and their receptors in human basophils. J Immunol. 2006;177:7322‐7331. doi.org/10.4049/jimmunol.177.10.73 22
• Marone G, Varricchi G, Loffredo S, Granata S. Mast cells and basophils in inflammatory and tumor angiogenesis and lymphangiogenesis. Eur J Pharmacol. 2015;778:146-151. doi.org/10.1016/j.ejphar.2015.03.088
• Agis H, Sperr WR, Herndlhofer S, et al. Clinical and prognostic significance of histamine monitoring in patients with CML during treatment with imatinib (STI571). Ann Oncol. 2007;18:1834‐ 1841. doi.org/10.1093/annonc/mdm 343
• Herrmann H, Sadovnik I, Cerny-Reiterer S, et al. Dipeptidylpeptidase IV (CD26) defines leukemic stem cells (LSC) in chronic myeloid leukemia. Blood 2014;123:3951‐3962. doi.org/10.1182/blood-2013-10-536078