Abstract 1733

Introduction:

Much remains to be elucidated regarding the etiology of myelodysplastic syndrome (MDS) and why some cases progress to acute myeloid leukemia. Further, there are few data on how accurate case classification is within state cancer registries and the impact of the 2008 WHO MDS classification modifications on clinical practice. We are conducting a large population-based prospective study of MDS to investigate risk factors for initial disease as well as disease progression. Our study includes comprehensive central review of all cases. Initial findings are reported here.

Methods:

We began evaluation and follow-up of all newly diagnosed MDS cases in Minnesota between the ages of 20 and 85 years from April 1, 2010 onward. Our process includes rapid case identification by the Minnesota Cancer Surveillance System (MCSS), contact of individual patients after primary physician approval, and, for interested patients, participation in an extensive questionnaire with medical history review and optional saliva sample for DNA. In concert, all cases pass through central medical review including: 1) independent pathology report +/− slide review by two hematopathologists to confirm diagnosis and subclassification; 2) independent cytogenetic review by a cytogeneticist; and 3) medical chart review by an oncologist to identify pertinent clinical history and prospectively calculate the International Prognostic Scoring System (IPSS) and WHO-based prognostic scoring system (WPSS) scores. Annual follow-up is planned to monitor for disease progression and outcome. In cases of unknown cytogenetics, IPSS calculations are not completed. In cases of unknown cytogenetics or diagnosis of MDS-U, not currently stratified in the WPSS, WPSS calculations are not completed.

Results:

We describe the first 67 patients enrolled on this study that have completed central review. The majority of patients were male (n=44) and the median age of the cohort at diagnosis was 71 (range 41–85). Table 1 

Table 1:

Patient Demographics

VariableTotal (n = 67)
Age:  
41-60 11 
61-70 15 
71-85 41 
IPSS Risk Category: #  
Low 17 
Intermediate-1 21 
Intermediate-2 23 
High 5 
WPSS: *  
Very Low 15 
Low 5 
Intermediate 9 
High 30 
Very High 5 
VariableTotal (n = 67)
Age:  
41-60 11 
61-70 15 
71-85 41 
IPSS Risk Category: #  
Low 17 
Intermediate-1 21 
Intermediate-2 23 
High 5 
WPSS: *  
Very Low 15 
Low 5 
Intermediate 9 
High 30 
Very High 5 
#

IPSS not calculable in 1 case due to missing cytogenetics

*

WPSS not calculable in 3 cases due to MDS-U (2) and no cytogenetics (1)

Concordance assessment of initial WHO diagnosis determined by MCSS and WHO diagnosis after central review found a total of 21 discordant diagnoses (31.3%). The discordant cases included: 10 cases initially diagnosed as MDS-U that central review further delineated into RA (1), RT(1), RARS (1), RCMD (3), RAEB (2), and therapy related MDS (2); 1 case originally classified as RA to MDS-U; 6 cases transitioned from RAEB to t-MDS (5) and RCMD (1); and 4 cases initially described as RCMD changed to MDS del 5q (1), RAEB (2), t-MDS (1). Table 2 

View Large
Table 2:

Comparison of WHO Classification

WHO Classification per MCSSWHO Classification after Central Review
Refractory Anemia (RA) 2 2 
Refractory Thrombocytopenia (RT)  1 
Refractory Anemia with Ringed Sideroblasts (RARS) 10 11 
Refractory Cytopenias with multilineage dysplasia (RCMD) 14 14 
Refractory Anemia with Excess Blasts (RAEB):   
–RAEB-1 29 9 
–RAEB-2  18 
MDS with deletion 5q 1 2 
MDS-Unclassifiable (MDS-U) 11 2 
Therapy related MDS (t-MDS)  8 
WHO Classification per MCSSWHO Classification after Central Review
Refractory Anemia (RA) 2 2 
Refractory Thrombocytopenia (RT)  1 
Refractory Anemia with Ringed Sideroblasts (RARS) 10 11 
Refractory Cytopenias with multilineage dysplasia (RCMD) 14 14 
Refractory Anemia with Excess Blasts (RAEB):   
–RAEB-1 29 9 
–RAEB-2  18 
MDS with deletion 5q 1 2 
MDS-Unclassifiable (MDS-U) 11 2 
Therapy related MDS (t-MDS)  8 
View Large
Conclusion:

Ours is the first large prospective population-based study of MDS that includes central pathology, cytogenetic, and clinical review of newly diagnosed patients with prospective calculation of IPSS and WPSS and plans for long term follow-up. This study is expected to enroll approximately 700 MDS cases over a five year period. While early in investigation, our initial review highlights the variability in distinct WHO diagnosis between initial cancer registry (i.e., MCSS) designation and designation after thorough central review of all appropriate diagnostic components. Our data suggest the robustness of the WHO RA, RARS, and RCMD classifications, the possible over-utilization of MDS-U classification, and highlight the under-representation of therapy-related MDS identification with registry designation. The impact of discordant diagnoses between MCSS and central review on therapeutic strategies is uncertain, but warrants continued evaluation and underscores the importance of complete central review in evaluation of MDS cases. Supported by NIH R01 CA142714.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
myelodysplastic syndrome, world health organization, refractory anemia with excess blasts, cytopenia, refractory, with multilineage dysplasia, prostatic hypertrophy risk score, refractory anemia with sideroblasts, follow-up, cancer, disease progression, cytopenia

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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