Abstract
The myelodysplastic syndromes (MDS) are a cluster of clonal hematopoietic disorders with diverse origins. MDS frequently progresses to secondary acute myeloid leukemia (sAML). sAML is unique from de novo AML and is associated with a poorer response to induction chemotherapy and decreased survival (Granfeldt Ostgard, et al 2015). To remedy this situation, we conducted a retrospective study of the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) database. A logistic regression analysis was performed to determine the significant risk factors associated with transformation of MDS into sAML. In addition, a Cox proportional hazard regression model was used to analyze the prognostic factors for survival of the included patients. Leukemic transformation was fitted in the Cox model as a time-dependent covariate.
A total of 36,558 patients with primary, newly-diagnosed MDS were identified in the SEER database during the study period (January 1, 2001 to December 31, 2013) and grouped on the basis of age (≤ 40 and > 40 years). This population is among the largest of any population based-study of MDS or sAML. Table 1 presents a summary of patient demographics and clinical characteristics for the 2 groups of patients, who differed significantly in gender, race, marital status, WHO classification, type of follow-up, and rate and time interval of leukemic transformation. Transformation occurred more frequently (3.7% vs. 2.5%) and more quickly (median time of transformation: 4 vs. 13 months) for patients in the under 40 group. Other studies have also identified a detrimental effect of age on the progression of MDS to sAML (Hulegardh, et al 2015, Shi, et al 2004). Table 2 summarize our analysis of overall survival (OS) and cancer-specific survival (CSS), respectively. For both groups of patients, refractory anemia with excess blasts had the worst prognosis for OS and CSS. Most histological types of MDS including therapy-related myeloid neoplasms were all significant indicators of poor survival when compared to refractory anemia, with the exception of refractory thrombocytopenia. We also found that the negative impact on survival of a subtype other than refractory anemia was greater for patients under 40, particularly for CSS.
Regarding demographic factors, older age and female gender were predictors of shorter and longer survival, respectively, with similar effects for each age group. Black race was positively associated with survival, when compared to being white and over 40 (the influence of race was not examined in the under 40 group). This study is among the first to assess the influence of marital status on the outcomes of patients with MDS. Our analysis revealed that being married was positively associated with OS and CSS for patients older than 40, when compared to being single, separated, divorced, or widowed.However, the effect of marital status could be related to race, as Martinez et al found that non-married white patients in the California Cancer Registry (CCR) had a greater risk of mortality than did non-married black, Hispanic, or Asian/Pacific Islander patients (Martinez, et al 2016).
In conclusion, we have conducted a retrospective analysis of the SEER cancer registry database. Our results indicate that younger patients not only had a greater likelihood of developing sAML than did older patients but also had a shorter time interval to transformation. Survival among older patients is influenced by demographic factors including age, gender, race, and marital status. Accordingly, the accuracy of current risk assessment systems may be improved by including these types of data.
*Correspondending author information: Dr. Jian Huang, Department of Hematology, The fourth Affiliated Hospital, College of Medicine, Zhejiang University. Email: househuang@zju.edu.cn.
Funding: Social development project of public welfare technology research, Zhejiang Provincial Department of science and technology, Zhejiang Province, China (2016C33160). Public technology research projects of Yiwu City, Zhejiang Province, China (2016-S-05).
No relevant conflicts of interest to declare.
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