Hastalık veya Risk Gruplarına Göre Sınıflandırılmış Akut Myeloid Lösemi Hastalarında Tedavideki Başarısızlık Sebeplerinin Değerlendirilmesi

Abstract

Çelebi G. Evaluation of Treatment Failure Reasons in Patients with Acute Myeloid Leukemia Classified According to Disease or Risk Groups, Hacettepe University Faculty of Medicine, Internal Medicine Specialty Thesis, Ankara, 2022. Acute myeloid leukemia (AML) is a life-threatening hematological malignancy that occurs in myeloid cell line as a result of some somatic mutations in the primitive multipotent hematological stem cell. It can be classified morphologically and cytogenetically. Prognosis is related to clinical features of patient and the cytogenetic features of the disease. Acute myeloid leukemia is an extremely heterogeneous disease and mortality is common in this heterogeneous disease, even in subgroups with the best prognosis. It is important to know the causes of failure in this disease and to evaluate them specifically according to subgroups in terms of patient follow-up and management. This study is a single-center observational retrospective cohort study in which adult patients followed up by Hacettepe University Hematology Department with the diagnosis of AML and whose first induction therapy were started in our center were evaluated in terms of clinical and demographic findings, treatment, cytogenetic and molecular results, and first treatment failure types. The aim of this study is to divide the disease into certain subgroups, to evaluate the first type of failure in each subgroup and to raise awareness about the situations that the physician may encounter in the follow-up of the patient in line with the results obtained, and to contribute to the literature in which there is a deficiency in this area. A retrospective observational cohort model was created using the electronic records of the patients for the study, which was conducted with 485 patients who met the study criteria. Failure in follow-up was observed in 66.2% of the patients. The actuarial median overall survival for patients receiving intensive therapy was 29.3 (16.1-46.4 confidence interval) months. 36 months survival rate was 48.1%. Patients were divided into subgroups as acute promyelocytic leukemia (APL), t(8;21) AML, inv(16) AML, intermediate risk de novo AML, adverse risk de novo AML, other de novo AML, treatment-related AML, and secondary AML. When those who received intensive treatment were evaluated, a significant difference was found between the first failure types according to the subgroups (p=0.008). It was seen that this difference was due to the distribution of induction mortality, refractoriness and relapse in the groups. When the reasons for first failure within the groups were evaluated, it was induction mortality for APL (71.4%), relapse for inv(16) AML (58.3%) and moderate risk de novo AML (47.2%), and refractoriness for poor risk de novo AML (54.5%), treatment-related AML (75.0%), and secondary AML (43.9%) groups. When the distributions for t(8;21) AML were evaluated, it was seen that a specific failure type was not evident. The first type of failure for the other de novo AML group, which had to be more heterogeneous in accordance with the grouping principles, was induction mortality in 33.6% and relapse in 32.8%. In conclusion, there is a significant difference in distribution of first treatment failure types in AML subtypes. It is important to know which first failure type should be expected in specific subgroups for more successful disease management. Larger studies on this subject would be useful. Key words: Acute myeloid leukemia, treatment failure, induction mortality, relapse, induction refractoriness, survival