Acute Myeloid Leukemia And Diverse Patient Survival Outcomes
Background
Cancer remains a prominent global health concern, accounting for a significant number of cases and fatalities worldwide in 2020, with projections indicating further increases in both incidence and mortality rates, particularly in the United States. Hematologic malignancies (HMs) constitute a substantial subset of cancers, comprising approximately 6.5% of all cancer cases globally and rising to 9% in the United States and Europe. Among HMs, the major subtypes include leukemias (divided into myeloid and lymphoid), Hodgkin lymphomas (HL), non-Hodgkin lymphomas (NHL), and multiple myelomas (MM).
Leukemias, being a distinct group of HMs, accounted for 474,519 new cases and 311,594 deaths worldwide in 2020. Notably, there have been recent shifts in the incidence rates of various leukemia types, with declines in acute lymphocytic leukemia (ALL) and chronic myeloid leukemia (CML), and increases in chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). Acute myeloid leukemia is the most common acute leukemia in adults and comprises approximately one-third of all diagnosed leukemias, with its incidence rising with age. Prognostically, AML is categorized into favorable, intermediate, and adverse risk groups. The treatment approach involves induction therapy to achieve complete remission, followed by post-remission therapy which may include chemotherapy and bone marrow transplantation.
Sex differences have been identified as important factors in cancer, with males exhibiting higher incidence and mortality rates compared to females, up to 20% and 40% respectively. Although the impact of sex differences on HMs is still not fully understood, reports consistently demonstrate a male predominance in acute myeloid leukemia incidence, particularly with increasing age. Recent comprehensive analyses across different cancer types have suggested an overall incidence rate about 1.4 times higher in males. On the other hand, survival data regarding sex differences in HMs are conflicting, with some studies showing better survival and prognosis for females, while others fail to establish significant differences between the sexes. Further research is warranted to gain a deeper understanding of the implications of sex differences in the context of AML and other hematologic malignancies.
The Study
The research was conducted at the University Hospitals (UH) Seidman Cancer Center, and patient data were gathered from the UH data repository, which utilizes the CAISIS platform. CAISIS is a web-based cancer data management system that integrates information from eight different sources related to cancer patients, such as Soarian, NGS Labs, Sunrise Clinical Manager, Tumor Registry, Via Oncology, OnCore, MosiaQ, PRO tools, and others.
To ensure patient privacy, all records were de-identified before being used in the study, and the research was ethically approved by the University Hospitals of Cleveland Institutional Review Board (IRB).
To ensure the utmost accuracy and completeness of patient information, data obtained from the UH database were further supplemented with electronic health records (EHR) gathered through EMERSE (Electronic Medical Record Search Engine).
A sensitivity analysis was conducted in various subgroups, including patients with a favorable diagnosis, patients diagnosed after 2015 (to account for temporal changes in treatment and practices), and patients with a history of at least one hospitalization. The cohort’s incidence and mortality findings were compared with those of the general US population, using data from the Surveillance, Epidemiology, and End Result (SEER) database.
Data from the SEER database were obtained through SEER*stat software, based on the SEER Research Plus database, which included acute myeloid leukemia patients diagnosed between 2010 and 2019, with the exclusion of those diagnosed with promyelocytic leukemia. The variables analyzed were categorized using a similar methodology to that applied to the UH database, and they included age at diagnosis, sex, race, ethnicity, chemotherapy usage, vital status, and median survival.
Study Limitations
This study has some limitations to consider. Firstly, some patients were referred to our institution for second opinions, potentially leading to incomplete or inaccurate information due to self-reporting. Additionally, as this is a study conducted at a single institution, some patients may have been lost to follow-up or sought emergency care elsewhere. The 10-year timeframe of the study also covers changes in cancer care practices over time.
Another limitation is the use of ICD codes to define treatment adverse events, which could result in an underrepresentation of such events. Furthermore, the available treatment variables did not allow us to categorize patients based on intensive chemotherapy. Factors like alcohol drinking or drug use were not available for consideration in the analysis. However, it is worth noting that our database integrates multiple sources, providing comprehensive and long-term patient information, a feature rarely seen in other databases. Additionally, as an oncology center, we maintain close patient follow-up. Moreover, the study’s statistical analyses are robust, and we conducted a sensitivity analysis in various groups, further enhancing the study’s reliability. Furthermore, the results were validated using a national database to strengthen the study’s findings and conclusions, which helps to mitigate these limitations.
Results
Between 2010 and 2022, a total of 1020 patients with acute myeloid leukemia (AML) were identified, representing 22,060 person-months of observation (Table 1). The cohort had a median age of 65 years, with an interquartile range (IQR) of 53 to 74 years. Among the patients, a majority were White (74.8%) and non-Hispanic (98.4%). The Charlson score, used to assess comorbidities, indicated that 44.3% of the patients had a score of 5 or higher.
Regarding treatment modalities, 9.9% of the patients had a favorable prognosis, 39.8% received chemotherapy, 2.6% underwent immunotherapy, and 11.4% received bone marrow transplantation (BMT). Additionally, 20.8% of the patients had at least one hospitalization record during the follow-up period. Among those who received any type of treatment, 33.1% experienced psychological issues, while 11.6% were diagnosed with cognitive decline or dementia.
Chemotherapy adverse events were observed in 57.2% of the patients who received this treatment. For those treated with immunotherapy, immune-related adverse events (irAEs) were diagnosed in 5.3% of cases, and BMT complications were reported in 74.1% of those who underwent this treatment.
The study included 1020 patients, with 42.6% (n=435) being females and 57.4% (n=585) being males, resulting in a male-to-female ratio of 1.34. In comparison to males, females exhibited higher rates of Black race (14% vs. 8.9%, p=0.03) and never smokers (43.9% vs. 32.8%, p<0.001), while having lower rates of RUNX1 mutation (2.1% vs. 5.3%, p=0.01).
Among all the patients analyzed, older age at diagnosis (aHR = 1.03, 95% CI 1.02–1.04) and the presence of a TP53 mutation (aHR = 2.24, 95% CI 1.69–2.97) were linked to an increased risk of death. Conversely, receiving chemotherapy (aHR = 0.72, 95% CI 0.57–0.92) and higher appointment completion rates (aHR = 0.98, 95% CI 0.98–0.98) were associated with a reduced risk of death.
Oncology Related Tools
Other
Latest Research
