Acute Myeloid Leukemia Treatment Outcomes: First Report from Single Center Retrospective Study in Kazakhstan

Acute myeloid leukemia (AML) is the most common hematological malignancy in adults. In the last decade, 2 internationally approved AML treatment guidelines, including hematopoietic stem cell transplantation are widely used in 3 Kazakhstan. The categorization of acute myeloid leukemia was done according to the French-American British 4 classification. The prognosis of patients at the time of diagnosis was determined by cytogenetic tests following the 5 guidelines of the European LeukemiaNet. The overall survival and event-free survival were analyzed using the Kaplan- 6 Meier method, and hazard ratios were defined with Cox regression. 7 Totally 398 patients with AML were treated in the National Research Oncology Center between 2010 and 2020. The 8 mean age was 38.3 years. We have found the correlation between ethnicity, cytogenetic group, white blood cell count, and 9 treatment approaches with overall and event-free survival. There was a significantly longer OS in a cytogenetic group 10 with a good prognosis compared with intermediate and poor prognosis. The median survival time in the group with a good 11 prognosis was 43 months, 23 months in the intermediate group (p=0.7), and 12 months in the poor prognosis group 12 (p=0.016). There was a significantly longer OS for the group of patients who received hematopoietic stem cell 13 transplantation (HSCT), 52 months versus 10 months in the group who received chemotherapy only, p-value < 0.0001. 14 Prognostic factors, such as cytogenetic group, initial WBC count, and treatment approaches are significantly associated 15 with patient survival. Our study data were consistent with previous reports. 16


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Totally 398 patients with AML were treated in the National Research Oncology Center between 2010 and 2020. The 8 mean age was 38.3 years. We have found the correlation between ethnicity, cytogenetic group, white blood cell count, and 9 treatment approaches with overall and event-free survival. There was a significantly longer OS in a cytogenetic group 14 Prognostic factors, such as cytogenetic group, initial WBC count, and treatment approaches are significantly associated 15 with patient survival. Our study data were consistent with previous reports.   According to the Kazakhstan National Cancer Institute, hematological malignancies represent 4.7% of all cancers, 5 th 2 place among both sexes in Kazakhstan. Morbidity due to hematological cancer is in 4 th place among all cancer-related 3 deaths in Kazakhstan [1]. Based on to Globocan data, 759 new cases of leukemia were registered in Kazakhstan in 2020, 4 which corresponds to the 14 th place among all cancers, the growth rate comprised 2% compared with 2019 [2]. Acute 5 myeloid leukemia (AML) is the most common acute leukemia in adults [3]. There are no data regarding the estimated 6 number of death due to AML in Kazakhstan. AML is a group of blood cell cancers originating from hematopoietic 7 precursors in the bone marrow and resulting in a conglomeration of poorly differentiated myeloid cells infiltrating bone 8 marrow, peripheral blood, and other organs [4]. Blood disorder develops due to the acquisition of chromosomal 9 translocations and multiple genetic mutations by leukemic stem cells [5][6][7]. Genetic events are usually associated with 10 environmental influence, other blood disorders, tobacco use, and previous chemotherapy [8-9]. It is well known that AML 11 incidence increases with age. The median age of people being diagnosed is 65 years [10]. Various factors were proved to 12 influence the AML incidence and clinical outcome. The incidence increases with age with approximately 2 and 20 cases

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we present a single-center experience of AML treatment outcome.

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The data were retrospectively analyzed, and all ethical principles of the Helsinki Declaration have been followed. The

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Ethical Committee of the National Research Oncology Center (permit number №11) approved the study.

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Acute myeloid leukemia classification 20 The further division of AML into its subtypes was done according to the French-American British (FAB) classification.

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It sorts AML from M0 to M7, depending on the type of cell where leukemia developed and the maturity of these cells 22 [13]. Moreover, this categorization takes into account the symptoms that show the whole picture of the patient's condition.    There were other antibiotics used in the frame of chemotherapy, and they were united in one category 'others'.

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Most common were febrile neutropenia, sepsis, and aspergillosis.   Figure 6). Our analysis showed that OS and EFS in a group of patients with white blood cell (WBC) lower than 30x10 9 /L 31 was significantly higher compared with the group with a WBC count of more than 30x10 9 /L at the time of diagnosis, 20 32 months vs 13 months and 17 months vs 10 months respectively (Figure 7). The median survival time for those, who 33 underwent allogeneic stem cell transplantation was 43 months, while for haploidentical stem cell transplantation patients 34 it was 39 months, and the difference was not statistically significant, p=0.28 (Figure 8).
We found that the development of febrile neutropenia after chemotherapy was significantly associated with a negative 1 outcome. In this study, 63.9 % of patients died; 67 % died due to the disease progression, the second most common cause 2 of death was an infection. 3

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The current study reports a 10-year single-center experience of AML treatment in Kazakhstan. The National Research 5 Oncology Center is one of the largest centers in Central Asia. In our study, we analyzed the incidence, death, and other 6 epidemiological data of AML, based on the medical record database of our center during the past 10 years. There is scarce 7 epidemiological data on AML in Kazakhstan.

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Although population data says that acute myeloid leukemia occurs mostly in adults [16], the mean age of our patients was 9 38 years. It can be explained by the fact that initially there was a selection bias to perform hematopoietic stem cell 10 transplantation. AML can be cured at younger ages more successfully than for those older than 60 years [17]. There is no 11 clear cut-off point in literature for age to predict prognosis; however, the separation as younger than 60 and older showed 12 significant results in both overall survival and event-free survival. Older individuals had for 160% more risk of death due 13 to disease (Figure 1a), and this result is consistent with other research outcomes [18].
14 The data showed significantly better event-free survival for females (HR=1.38). The trend of higher survival rates among 15 women diagnosed with AML also was previously reported [19]. However, the cause of this phenomenon is still to be

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The primary induction therapy with IDA showed a significant association with a favorable outcome compared to

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The data that support the findings of this study are available from the corresponding author upon reasonable request.                Figure 1