An Analysis of Real Life Data Obtained from 30 Years Follow-up of Primary Myelodysplastic Syndromes (MDS) Patients Confirms a Leading Role of Stem Cell Transplantation (SCT) for Achievement of Prolonged Survival
Authors: Cermak Jaroslav , Vitek Antonin , Mikulenkova Dana , Soukupova Jacqueline , Brezinova Jana , Stastna Marketa , Valkova Veronika , Belickova Monika , Michalova Kyra , Cetkovsky Petr 
Published: October 2019

Abstract
AIM OF THE STUDY, PATIENTS AND METHODS : The data obtained from a long-term follow-up for a period of 30 years (1988-2017) were analyzed in a group of 529 patients with primary MDS and factors affecting prolonged survival were detected using different statistical methods including Kaplan Maier test and multivariate analysis.
RESULTS : The results confirmed usefulness of both IPSS and IPSS-R (median survival in months for risk groups : very low - 73.7, low - 40.0, intermediate - 27.0, high - 9.0, very high - 3.5). In a subgroup of 249 patients with less advanced disease without excess of blasts, allogeneic SCT represented the most favouring treatment approach leading to estimated 10 years survival in 49.1% of patients. However, when compared to patients treated by supportive care only, a benefit in overall survival for SCT did not become significant before 5 years of follow-up (estimated 5 years survival /e5yS/: 43.3% for supportive care vs. 54.7 % for SCT). Only 2 (3.8%) out of 53 transplanted patients died later than after 5 years follow-up in comparison to 31 (20.8%) out of 149 patients on supportive care; 22 of them died on complications not directly related to MDS and a late disease progression (between 6 and 26 years after diagnosis of MDS) was observed in 9 patients. Transplantation related mortality was 30.2%, SCT at the time of disease progression (>5% of bone marrow /BM/ blasts) and prolonged (>3 months) administration of corticosteroids prior to SCT were independent adverse prognostic factors for SCT outcome (P<0.001). Special treatment approaches were effective in selected subgroups of patients : rHuEPO in patients with sEPO < 100 IU/l and ≤ 2 TU of RBC/month, lenalidomide in patients with isolated del(5q) and ATG in hypoplastic MDS with e5yS of 63.6%,75.0% and 83.3%, respectively. In 169 patients with advanced MDS ( ≥ 10% BM blasts), allogeneic SCT was the only treatment option leading to prolonged survival ( e5yS: 48,9%). The difference between efficiency of SCT and treatment with hypomethylating agents (HMA) became significant after 2 years of follow-up, estimated 3years survival was 53,2% for SCT and 26.9% for HMA, e5yS for HMA was only 3.8%. The differences were similar in a subset of patients older than 50 years of age (e5yS for SCT: 31.3%, for HMA: 3.2%). Reduction of BM blasts below 10% prior to SCT was an important factor affecting outcome of patients (median survival 62.3 months for those transplanted with < 10% BM blasts vs. 17.0 months for those with ≥ 10% BM blasts /P<0.001/). The type and intensity of conditioning did not affect outcome of SCT. Seven (14.9%) out of 47 transplanted patients relapsed, all of them within 3 years after SCT, 6 of them entered SCT with ≥ 10% BM blasts. Only 3 (6.4%) SCT patients died later than 5 years after SCT. Introduction of HMA improved short term outcome of patients not indicated for SCT ( estimated 1 year survival for HMA was 80.8% vs. 41.3% for combination chemotherapy and 52.9% for low dose ARA-C) but only minimum (4.1%) of non-transplanted patients survived 5 years.
CONCLUSIONS : The analysis of long-term follow-up showed that younger patients with less advanced MDS without excess of blasts and adverse prognostic factors should be transplanted as soon as possible after diagnosis before disease progression. An advantage of more conservative approach to patients with early disease who are not indicated for SCT was confirmed by presence of a relatively high number of patients surviving 5 years with supportive care only. SCT represented the treatment of choice for advanced MDS and reduction of BM blasts prior to SCT siginficantly affected outcome of SCT. Administration of HMA significantly improved short term survival but did not affect long term outcome of patients.

Disclosures
No relevant conflicts of interest to declare.