Characteristics of Disease Progression in 3213 Patients with Myelodysplastic Syndrome
Authors: Zohren Fabian , Strupp Corinna , Kuendgen Andrea , Giagounidis Aristoteles , Hildebrandt Barbara , Suter Ulrich , Gattermann Norbert , Haas Rainer , Germing Ulrich 
Published: April 2020

Abstract
Myelodysplastic Syndromes (MDS) are hematopoietic stem cell disorders, which are characterized by marrow failure and a substantial risk of developing Acute Myeloid Leukemia (AML). While some patients gradually progress to more advanced MDS subtypes, others experience an apparently immediate AML onset without any transition period. In order to get a better understanding of these different types of MDS progression, we retrospectively analyzed the data of 3213 patients included into the MDS registry Düsseldorf. As assessed by bone marrow examination a disease progression to AML or to advanced MDS subtype was observed in 24,5% of the patients. The progression rate was lowest in the unilineage dysplasia group (RA/RARS: 9%) as compared to 5q- (26%), multilineage dysplasia (16%), RAEB I (26%) and RAEB II (37%). The progression rate in CMML I was 17%, in CMML II 31%, in RARS-T 9% and in the former RAEB-T group 57%. We then evaluated the survival-time of the progressive patients. In the entire group, patients who progressed had a median survival of 17 months compared to 30 months in those with stable disease (p=0.0005). In the group of patients with less than 5% of medullary blasts at time of diagnosis, those who progressed had a median survival of 28 months compared to 48 months in those who did not progress (p=0.00005). Interestingly, in this group of patients disease progression into an advanced MDS subtype did not affect survival (4% progression in advanced subtype, 46 vs. 48 months, p= n.s.), whereas disease progression into AML was associated with a shorter survival (11% progression into AML, 23 vs. 48 months, p=0,0005) In the group of patients who had &gt;5% of medullary blasts at diagnosis, the progression did not influence survival substantially (14 vs.15 months, p=0.01). The cumulative risk of AML evolution at 2 and 5 years after initial diagnosis was lowest in unilineage dysplasia (4% and 8%), multilineage dysplasia (11% and 19%), 5q- (10% and 18%), RAEB I (26% and 44%), RAEB II (50% and 74%), CMML I (14% and 24%), CMML II (33% and 74%), RARS-T (5% and 5%) and RAEB –T (70% and 77%). In the following we investigated the course of MDS progression in those patients who did not develop AML. Fifty-three % of the patients in the unilineage group (RA/RARS) progressed to RAEB I or RAEB II, 10% to RCMD and 3% developed a 5q- syndrome. In the multilineage group 41% of the patients transformed into RAEB I or II, while 40% of the patients with 5q- progressed to RAEB I or RAEB II. In the RAEB I group, 28% of the patients developed RAEB II and 18% of the CMML I patients ended up as CMML II. Finally, we analyzed the effect of progression within the IPSS groups with regard to survival. Patients within the low risk group who progressed (22%) had a median survival of only 46 months, compared to 88 months among those who did not progress (p=0.00005). This correlation was also significant among patients within the intermediate I group (29% progressive patients, 26 vs. 36 months, p=0.0004). In both, the intermediate II and the high risk group progression was not associated with a shorter survival.
Conclusions:
About 25% of the patients progress to a more advanced MDS type or to AML. A substantial part of the patients with 5q- Syndrome as well as patients with multilineage dysplasia and RAEB types show disease progression. Progression is only associated with a shorter survival among patients within the IPSS low and Intermediate I risk group. In patients with less than 5% of marrow blasts at time of diagnosis only progression into AML is associated with a shorter survival.