Survival, Prognostic Factors, and Rates of Leukemic Transformation in a Multicenter Study of 303 Untreated Patients with MDS and Del(5q).
Authors: Germing Ulrich , Lauseker Michael , Hildebrandt Barbara , Symeonidis Argiris , Cermak Jaroslav , Pfeilstöcker Michael , Nösslinger Thomas , Sekeres Mikkael A. , Maciejewski Jaroslaw P. , Haase Detlef , Schanz Julie , Seymour Jf , Weide Rudolf , Lübbert Michael , Platzbecker Uwe , Valent Peter , Götze Katharina , Stauder Reinhard , Blum Sabine , Kreuzer Karl Anton , Schlenk Richard F. , Aul Carlo , Kündgen Andrea , Hasford Joerg , Giagounidis Aristoteles 
Published: October 2019

Abstract 945

In 2001, the WHO defined the category MDS with del(5q) due to unique cytogenetic, morphologic, hematologic, clinical, prognostic and therapeutic features. The survival of these patients, as well as patients with refractory cytopenia with unilineage dysplasia (RCUD) and refractory anemia with ring sideroblasts is favorable in comparison to other MDS types. Data on disease progression to a more advanced MDS category or to acute leukemia (AML) are sparse and have not been examined in detail. In order to address this issue we collated data of all patients with MDS and del(5q) characterized by low or intermediate-1 IPSS risk score that had been included into various collaborating MDS registries. Patients were followed from diagnosis and data on cell counts, transfusion dependency, and MDS progression were documented. No patients received treatment other than best supportive care. The status of 62 patients was censored at the time of the initiation of Lenalidomide therapy. AML progression was defined as >20% marrow blasts. Estimates of survival probability were calculated with the Kaplan-Meier method. The cumulative incidence of progression to AML was calculated both with the Kaplan-Meier method and with the competing risk method where “death without progression to AML” is considered as competing event, not as censoring. For both events the cumulative incidences are estimated simultaneously. This method has the advantage that it takes into account that there is a difference between end of follow-up and death. Depending on the number of competing events, the curves are lower than those calculated with the Kaplan-Meier estimator.

We identified 303 patients, median age at diagnosis 65 years (28-91), 71% were females. Median follow up time was 3 years. Median survival was 71.5 months. Patients with del(5q) as a sole chromosomal aberration had a median survival of 73 months as compared to 19.3 months in patients with more than 1 additional aberrations. Patients who had red cell transfusion need at diagnosis had a median survival of 39 months vs. 97 months in transfusion independent patients (p=0.00005). Transfusion need at diagnosis was the most important parameter for survival. Patients in the WPSS very low risk group had a median survival of 107 months, as compared to 73 and 56 months in the low and intermediate risk group and 37 months in the high risk group.

44 of the 303 patients (15%) progressed to AML (>20% marrow blasts). The cumulative AML progression rate calculated with the Kaplan-Meier method was 7% at 2 years and 18.2% at 5 years. The cumulative risk of AML progression calculated with the competing risk method was 6.6% at 2 years and 15.1% at 5 years. Factors associated with the risk of AML transformation were intermediate-I IPSS risk and high risk WPSS score, marrow blast count >5%, and red-cell transfusion need at diagnosis. Survival and progression rates did not differ among the participating centers.

In conclusion, survival of patients with MDS and del(5q) is high and is comparable to patients with RCUD and RARS, but is associated with a risk of AML-transformation similar to RCMD without del(5q). Further cytogenetic and molecular studies are warranted in order to identify patients at greater risk of progression.

Disclosures:

Germing: Novartis, Celgene: Honoraria, Research Funding. Lauseker:Celgene: Research Funding. Hildebrandt:Celgene: Research Funding. Symeonidis:Celgene: Research Funding. Cermak:Celgene: Research Funding. Pfeilstöcker:Celgene: Research Funding. Nösslinger:Celgene: Research Funding. Sekeres:Celgene: Research Funding. Maciejewski:Celgene: Research Funding. Haase:Celgene: Research Funding. Schanz:Celgene: Research Funding. Seymour:Celgene: Research Funding. Weide:Celgene: Research Funding. Lübbert:Celgene: Research Funding. Platzbecker:Celgene: Research Funding. Valent:Celgene: Research Funding. Götze:Celgene: Research Funding. Stauder:Celgene: Research Funding. Blum:Celgene: Research Funding. Kreuzer:Celgene: Research Funding. Schlenk:Celgene: Research Funding. Aul:Celgene: Research Funding. Kündgen:Celgene: Research Funding. Hasford:Celgene: Research Funding. Giagounidis:Celgene: Research Funding.