Akut Miyeloid Lösemide FLT3 Mutasyonlarının Araştırılması: Hasta Sonuçları ve Tedavi Stratejileri Üzerine Tek Merkezli Gerçek Yaşam Verisi
Abstract
Akut Miyeloid Lösemi (AML), önemli ölçüde genetik heterojeniteye sahip karmaşık bir hematolojik malignitedir. Fms benzeri tirozin kinaz 3 (FLT3) mutasyonları, kötü prognoz ile ilişkilidir ve AML vakalarının yaklaşık %30'unda görülür. Bu çalışma, bir AML hasta kohortunda FLT3 mutasyonlarının prevalansını, bunların klinik sonuçlar üzerindeki etkilerini ve çeşitli tedavi yaklaşımlarının etkinliğini araştırmaktadır. Yaşları 20-95 arası 157 akut promiyelositik lösemi dışı de novo AML tanılı hasta FLT3-ITD ve FLT3-TKD mutasyonları açısından taranarak incelendi. Kemoterapiyi yaşa, ECOG performans durumuna ve FLT3 mutasyon varlığına göre uyarlandı. Araştırmamız hastaların %27,3'ünde FLT3 mutasyonu, %65'inde FLT3-ITD ve %35'inde FLT3-TKD mutasyonu olduğunu ortaya koydu. FLT3 mutasyonları olanlar, mutasyonları olmayan hastalara kıyasla daha yüksek ölüm oranları sergiledi. Yaş, FLT3 mutasyon durumu ve tekrarlayan/dirençli hastalık, mortalite için bağımsız risk faktörleri olarak ortaya çıktı. Midostaurin ile tedavi edilen hastalar, sorafenib uygulananlara göre daha düşük bir ölüm riskine sahipti. Bu çalışma, AML'deki FLT3 mutasyonlarının önemini, bunların klinik sonuçlar üzerindeki etkilerini ve hedefe yönelik tedavilerin avantajlarını vurgulamaktadır. Bulgularımız, FLT3 mutasyonları olan AML hastalarının prognozunu güçlendirmeyi amaçlayan daha ileri araştırmaların aciliyetini vurgulamaktadır.
Supporting Institution
YOK
Project Number
YOK
Thanks
Çukurova Üniversitesi Tıp Fakültesi Patoloji, Radyoloji, Nükleer Tıp Ana Bilim Dallarına Teşekkür Ederiz.
References
- 1. Döhner, H., Weisdorf, D. J., & Bloomfield, C. D. (2015). Acute myeloid leukemia. New England Journal of Medicine, 373(12), 1136-1152.
- 2. Papaemmanuil, E., Gerstung, M., Bullinger, L., Gaidzik, V. I., Paschka, P., Roberts, N. D., ... & Campbell, P. J. (2016). Genomic classification and prognosis in acute myeloid leukemia. New England Journal of Medicine, 374(23), 2209-2221.
- 3. Stirewalt, D. L., & Radich, J. P. (2003). The role of FLT3 in haematopoietic malignancies. Nature Reviews Cancer, 3(9), 650-665.
- 4. Döhner, H., Estey, E., Grimwade, D., Amadori, S., Appelbaum, F. R., Büchner, T., ... & Larson, R. A. (2017). Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood, 129(4), 424-447.
- 5. Stone, R. M., Mandrekar, S. J., Sanford, B. L., Laumann, K., Geyer, S., Bloomfield, C. D., ... & Döhner, K. (2017). Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. New England Journal of Medicine, 377(5), 454-464.
- 6. Daver, N., Schlenk, R. F., Russell, N. H., & Levis, M. J. (2019). Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia, 33(2), 299-312.
- 7. Alvarado, Y., Kantarjian, H. M., Luthra, R., Ravandi, F., Borthakur, G., Garcia-Manero, G., ... & Cortes, J. E. (2018). Treatment with FLT3 inhibitor in patients with FLT3-mutated acute myeloid leukemia is associated with development of secondary FLT3-tyrosine kinase domain mutations. Cancer, 120(14), 2142-2149.
- 8. Burchert, A., Bug, G., Fritz, L. V., Finke, J., Stelljes, M., Röllig, C., ... & Wagner, E. M. (2019). Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3–Internal Tandem Duplication Mutation (SORMAIN). Journal of Clinical Oncology, 37(26), 2329-2339.
- 9. Cortes, J. E., Khaled, S., Martinelli, G., Perl, A. E., Ganguly, S., Russell, N., ... & Bixby, D. (2019). Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. The Lancet Oncology, 20(7), 984-997.
- 10. Perl, A. E., Martinelli, G., Cortes, J. E., Neubauer, A., Berman, E., Paolini, S., ... & Levis, M. J. (2019). Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. Blood, 134(6), 981-988
- 11. Chen, W., Xie, H., Wang, H., Chen, L., Sun, Y., Chen, Z., ... & Huang, X. (2015). Prognostic significance of KIT mutations in core-binding factor acute myeloid leukemia: a systematic review and meta-analysis. PloS one, 10(3), e0121218.
- 12. Yalniz, F. F., Abou Dalle, I., Kantarjian, H., Borthakur, G., Kadia, T., Patel, K., ... & Ravandi, F. (2018). Prognostic significance of baseline FLT3-ITD mutant allele level in acute myeloid leukemia treated with intensive chemotherapy with/without sorafenib. American Journal of Hematology, 93(2), 164-171.
Investigating FLT3 Mutations in Acute Myeloid Leukemia: A Single-Center Real-World Data Study on Patient Outcomes and Treatment Strategies
Abstract
Acute Myeloid Leukemia (AML) is a complex hematological malignancy with considerable genetic heterogeneity. Fms-like tyrosine kinase 3 (FLT3) mutations are associated with poor prognosis and occur in nearly 30% of AML cases. This study delves into the prevalence of FLT3 mutations, their impact on clinical outcomes, and the efficacy of various treatment approaches in a cohort of AML patients. We examined 157 de novo non-acute promyelocytic leukemia AML patients aged 20-95 years, screening for FLT3-ITD and FLT3-TKD mutations. We tailored chemotherapy based on age, ECOG performance status, and FLT3 mutation presence. Our research revealed that 27.3% of patients harbored FLT3 mutations, with 65% FLT3-ITD and 35% FLT3-TKD mutations. Those with FLT3 mutations exhibited higher mortality rates compared to patients without mutations. Age, FLT3 mutation status, and relapsed/refractory disease emerged as independent risk factors for mortality. Patients treated with midostaurin faced a lower mortality risk than those administered sorafenib. This study underscores the significance of FLT3 mutations in AML, their influence on clinical outcomes, and the advantages of targeted therapies. Our findings stress the urgency for further investigation aimed at enhancing the prognosis for AML patients with FLT3 mutations.
Project Number
YOK
References
- 1. Döhner, H., Weisdorf, D. J., & Bloomfield, C. D. (2015). Acute myeloid leukemia. New England Journal of Medicine, 373(12), 1136-1152.
- 2. Papaemmanuil, E., Gerstung, M., Bullinger, L., Gaidzik, V. I., Paschka, P., Roberts, N. D., ... & Campbell, P. J. (2016). Genomic classification and prognosis in acute myeloid leukemia. New England Journal of Medicine, 374(23), 2209-2221.
- 3. Stirewalt, D. L., & Radich, J. P. (2003). The role of FLT3 in haematopoietic malignancies. Nature Reviews Cancer, 3(9), 650-665.
- 4. Döhner, H., Estey, E., Grimwade, D., Amadori, S., Appelbaum, F. R., Büchner, T., ... & Larson, R. A. (2017). Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood, 129(4), 424-447.
- 5. Stone, R. M., Mandrekar, S. J., Sanford, B. L., Laumann, K., Geyer, S., Bloomfield, C. D., ... & Döhner, K. (2017). Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. New England Journal of Medicine, 377(5), 454-464.
- 6. Daver, N., Schlenk, R. F., Russell, N. H., & Levis, M. J. (2019). Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia, 33(2), 299-312.
- 7. Alvarado, Y., Kantarjian, H. M., Luthra, R., Ravandi, F., Borthakur, G., Garcia-Manero, G., ... & Cortes, J. E. (2018). Treatment with FLT3 inhibitor in patients with FLT3-mutated acute myeloid leukemia is associated with development of secondary FLT3-tyrosine kinase domain mutations. Cancer, 120(14), 2142-2149.
- 8. Burchert, A., Bug, G., Fritz, L. V., Finke, J., Stelljes, M., Röllig, C., ... & Wagner, E. M. (2019). Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3–Internal Tandem Duplication Mutation (SORMAIN). Journal of Clinical Oncology, 37(26), 2329-2339.
- 9. Cortes, J. E., Khaled, S., Martinelli, G., Perl, A. E., Ganguly, S., Russell, N., ... & Bixby, D. (2019). Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. The Lancet Oncology, 20(7), 984-997.
- 10. Perl, A. E., Martinelli, G., Cortes, J. E., Neubauer, A., Berman, E., Paolini, S., ... & Levis, M. J. (2019). Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. Blood, 134(6), 981-988
- 11. Chen, W., Xie, H., Wang, H., Chen, L., Sun, Y., Chen, Z., ... & Huang, X. (2015). Prognostic significance of KIT mutations in core-binding factor acute myeloid leukemia: a systematic review and meta-analysis. PloS one, 10(3), e0121218.
- 12. Yalniz, F. F., Abou Dalle, I., Kantarjian, H., Borthakur, G., Kadia, T., Patel, K., ... & Ravandi, F. (2018). Prognostic significance of baseline FLT3-ITD mutant allele level in acute myeloid leukemia treated with intensive chemotherapy with/without sorafenib. American Journal of Hematology, 93(2), 164-171.
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | Research Articles |
| Authors | |
| Project Number | YOK |
| Publication Date | September 6, 2023 |
| Submission Date | May 17, 2023 |
| Published in Issue | Year 2023 Volume: 37 Issue: 2 |
