Abstract
Background:
Acute Myeloid Leukemia with myelodysplasia-related changes (AML-MRC), formerly known as the Acute myeloid leukemia with multilineage dysplasia is a distinct hematological disorder characterized by the presence of more than 20% blasts in peripheral blood or bone marrow and dysplasia in 50% or more of the cells in two or more myeloid cell lineages in the absence of recurrent cytogenetic abnormalities seen in AML and with no prior history of cytotoxic treatment for an unrelated disease (2). The presence of myelodysplasia was considered an independent prognostic factor in the past until it was disputed in a study by Wandt et al in 2008 (4). This heterogeneous disorder is associated with poor prognosis only when associated with Myelodysplastic syndrome (MDS) related cytogenetic abnormalities and are preceded by MDS, which is the majority(3). Induction chemotherapy is the treatment of choice in young healthy patients and hypomethylating agents (HMA) such as azacitadine and decitabine have been used in elderly patients who are unfit to receive induction chemotherapy if they are treatment naive(1). No significant advancements have been made in the treatment of this category of AML in the elderly patients with previous history of MDS treated with HMA. Our objective is to evaluate the survival trends of this entity over the last decade.
Methods:
We utilized National Cancer Institute Surveillance, Epidemiology, and End Results (SEER-18) database to identify adult patients with Acute Myeloid Leukemia (AML) with myelodysplastic related features. Several cohorts were categorized by race, gender and age were categorized. We grouped patients into three different time periods as: 2000-2004, 2005-2009 and 2010-2013. 1-year and median overall survival (OS) were computed using Kaplan Meier Curve and log rank test. Cox proportional hazard model was used for multivariate analysis.
Results:
The database comprised of 1733 patients from 2000-2013. Majority of the patients were male Caucasians, aged 60- 79 years. Median overall survival among the different year of diagnosis cohort was found to be comparable by KM curve (6 months, 6 months and 7 months for 2000-2004, 2005-2009 and 2010-2013 respectively) with p value of 0.112 by log rank test. On multivariate analysis using cox PH model, after adjusting for age, sex, race, income and area of residence, survival among patients in 2010 to 2013 was found to be significantly better compared to 2000 to 2004 (HR of 0.84, 95% confidence interval of 0.73 to 0.97, P 0.015). The one year OS rate was 35.7 % ±2, 30.3 % ±1.8, 31.7 % ±2.3 for 2010-2013, 2005-2009 and 2000-2004 cohorts respectively.
Conclusion:
Survival for patients with AML-MRC has improved over the decade, most likely attributable to improved supportive care since there hasn't been any major breakthrough in treatment of these patients.
References
1) Dombret, H., Seymour, J. F., Butrym, A., Wierzbowska, A., Selleslag, D., Jang, J. H., Kumar, R., Cavenagh, J., Schuh, A. C., Candoni, A., Récher, C., Sandhu, I., Bernal del Castillo, T., Al-Ali, H. K., Martinelli, G., Falantes, J., Noppeney, R., Stone, R. M., Minden, M. D., McIntyre, H., Songer, S., Lucy, L. M., Beach, C. L., & Döhner, H. (2015). International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood, 126(3), 291-299. Accessed August 02, 2017.
2) Brunning RD, Matutes E, Harris NL, et al. Acute myeloid leukemia with multilineage dysplasia. In: Jaffe E, Harris NL, Stein H, et al, eds. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. 3rd ed. Lyon, France: IARC; 2001:88-89.
3) Huck A, Pozdnyakova O, Brunner A, Higgins JM, Fathi AT, Hasserjian RP. Prior cytopenia predicts worse clinical outcome in acute myeloid leukemia. Leuk Res. 2015 Oct. 39 (10):1034-40.
4) Wandt H, Schakel U, Kroschinsky F, et al. MLD according to the WHO classification in AML has no correlation with age and no independent prognostic relevance as analyzed in 1766 patients. Blood. 2008;111:1855- 1861.
No relevant conflicts of interest to declare.
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