Abstract

Introduction

Much remains unknown regarding the etiology of MDS and why some cases progress to acute myeloid leukemia (AML). With MDS reportable as a distinct myeloid malignancy for the first time only in 2001, there are few data on state cancer registry case identification and classification accuracy. To grasp the true incidence and the scope of this heterogeneous clonal hematopoietic malignancy, the accuracy of such information is essential. In our third year of a large population-based prospective study of MDS to investigate risk factors for initial diagnosis and disease progression, we report our experience with MDS case identification and classification according to both our state cancer registry and our comprehensive central review process

Methods

We began our identification and follow-up of all newly diagnosed adult MDS cases in Minnesota in April 2010. Our process includes rapid case identification by the Minnesota Cancer Surveillance System (MCSS), contact of individual patients, and their participation in an extensive questionnaire and medical history review. In concert, all cases pass through central medical review including: 1) independent pathology review by two hematopathologists; 2) independent cytogenetic review by a cytogeneticist; 3) integrated central pathology-cytogenetic review; and 4) medical chart review by an oncologist to identify pertinent clinical history and treatments and prospectively calculate risk stratification scores (International Prognostic Scoring System (IPSS)). Annual follow-up monitors for disease progression and outcome.

Results

We describe the first 161 patients enrolled who have completed central review.

Table 1

Patient Demographics

DemographicN=161 (%)
Sex  
Male 111 (69%) 
 Female 50 (31%) 
Age  
<60 26 (16%) 
60+ 135 (84%) 
IPSS:  
Low 47 (30%) 
INT-1 43 (28%) 
INT-2 57 (37%) 
High 8 (5%) 
DemographicN=161 (%)
Sex  
Male 111 (69%) 
 Female 50 (31%) 
Age  
<60 26 (16%) 
60+ 135 (84%) 
IPSS:  
Low 47 (30%) 
INT-1 43 (28%) 
INT-2 57 (37%) 
High 8 (5%) 
Table 2

Comparison of WHO Classification: MCSS vs. Central Review

Central Review WHO (2008) Diagnosis
Total
MCSS Diagnosis RA RN RT RARS RCMD RAEB-1 RAEB-2 5q- t-MDS MDS-U  
RA        
RARS    20      23 
RCMD     19  25 
RAEB     14 26   50 
5q-          
t-MDS         
MDS-U  24 
Total 21 39 18 30 17 137 
Central Review WHO (2008) Diagnosis
Total
MCSS Diagnosis RA RN RT RARS RCMD RAEB-1 RAEB-2 5q- t-MDS MDS-U  
RA        
RARS    20      23 
RCMD     19  25 
RAEB     14 26   50 
5q-          
t-MDS         
MDS-U  24 
Total 21 39 18 30 17 137 

Note: Twenty four MDS cases were identified by individual institutions and not yet classified by MCSS. Our comparison table evaluates only those 137 cases with both MCSS and central review WHO classification.

RA=Refractory Anemia; RARS= Refractory anemia with ringed sideroblasts; RCMD= Refractory cytopenias with multilineage dysplasia; RAEB=Refractory anemia with excess blasts; t-MDS=therapy related MDS; MDS-U=MDS unclassified.

Our data highlight the excellent concordance between MCSS and central review for the MDS subtypes RAEB (n=40/50, 80%), RARS (n=20/23, 87%), and RCMD (n=19/25, 76%). However, we noted poor concordance for the MDS subtypes RA (n=1/7 (14%) with 5 cases re-classified as RCMD) and MDS-U (n=3/24(13%) with 21 cases re-classified into other MDS subtypes). Notably, our integrated central review process identified and reclassified 12 additional cases of t-MDS when all data were considered. Our central review process noted an additional 30 cases classified as MDS by MCSS that we deemed ineligible after central review due to insufficient morphology (n=20) or reclassification to chronic myelomonocytic leukemia (CMML) (n=5), MDS/MPD (n=3), or AML (n=4).

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 risk stratification calculation and long term follow-up. Our review highlights the variability in the diagnosis and subclassification of MDS between our state cancer registry and after integrated central review, with as many as 80% of cases in certain MDS subtypes being re-classified, and an approximately 20% ineligibility rate. The high proportion of cases submitted in MCSS as MDS-U that were re-classifiable into specific MDS subtypes following central review suggests a possible misapplication of this MDS category in a way not intended by the 2008 WHO guidelines. The additional classification of t-MDS by our central review process suggests that this subtype is likely underestimated by cancer registries. Assessment of therapeutic implications will be important to determine if these variabilities are consequential.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.