Treatment with Erythropoietic Stimulating Agents in IPSS Lower Risk MDS: Outcome Comparison Between 5q- and Non 5q- MDS Cases

In IPSS lower-risk Myelodysplastic Syndromes (MDS), anemia is the main therapeutic challenge. Erythropoietin stimulating agents (ESAs) can frequently correct anemia, but not all patients respond, and median response duration to ESAs is around 2 years (Park, Blood 2008;111:574). Patients with deletion of chromosome 5q are usually considered refractory to ESAs. Endogenous serum erythropoietin levels have been demonstrated in only one study to be higher in patients carrying del5q than in patients with Lower-Risk MDS and different abnormalities in karyotypes. Aims. We wanted to further analyze differences in management, efficacy and tolerability of ESAs therapy between MDS with and without del5q. Patients and Methods. We studied 239 MDS patients affected by IPSS low and intermediate 1 risk disease. 82 patients carried deletion of 5q, 12/82 in association with other anomalies. MDS patients with del 5q were WHO diagnosed as 9 RA, 9 RCMD, 13 RAEB-1, 47 5q minus syndrome and 2 unclassifiable MDS and divided by IPSS risk: 49 low risk and 33 INT-1. Patients without del5q were diagnosed as follows: 59 RA, 24 RARS, 43 RCMD, 17 RAEB-1, 4 CMML and 10 unclassifiable MDS. When subdivide per IPSS risk: 90 low risk and 67 INT-1. 75% of patients with del5q were female against 37% of patients without del5q. Medical record of patient were collected and reviewed, statistical analysis were perform with SPSS software. IWG criteria for response to ESA treatment were applied. Results. Endogenous erythropoietin (EPO) level at diagnosis were significant higher in patients with del 5q (mean 599,6 mU/ml) than in others (mean 99,3 mU/ml)(p=0.002). There was no significant difference, in terms of endogenous EPO levels, either stratifying by WHO classification (p=0.996) or by IPSS score (INT-1 325.8 mU/ml, low 138.6 mU/ml, p=0.120), or blast % (p>0.05). Serum creatinine levels were correlated with endogenous EPO levels (p=0.003 Spearman's rho −0.258). Serum Epo was also correlated to age (p=0.026 Spearman's rho −0.183). No correlation was seen between number of transfusions at diagnosis and serum EPO levels and between hemoglobin levels and serum EPO levels. 18 patients (22%) with deletion of 5 q responded to ESAs treatment versus 56,8% of responding patients without del 5q (p<0.001). Erythroid response was shorter p<0.05 in MDS with del5q. ESA response was inversely correlated with endogenous serum EPO levels (p=0.000). In all of our cohort rate of response to ESA was lower in patients with excess of blast than the others (32% vs 49% p=0,022). Conclusion. ESAs treatment has to be considered first line therapy for IPSS lower risk MDS patients with syntomatic anemia, also when carrying del5q. Endogenous EPO levels are constantly higher, throughout disease history, in del5q MDS cases. This could account for worse ESA response. Anemia and WHO classification do not seem to influence ESA response. Excess of blasts was an adverse prognostic factor to ESA response with or without del5q. A deeper insight into mechanisms of resistance to ESAs is needed.

No relevant conflicts of interest to declare.