Outcomes of Patients with Myelodysplastic Syndromes/Myeloproliferative Neoplasms with Emphasis On MDS/MPN-Unclassified
Authors: Kelaidi Charikleia , Constantinou Varnavas , Papaioannou George , Stavroyianni Niki , Vadikoliou Chrysanthi , Sotiropoulos Damianos , Saloum Riant , Papadaki Theodora , Athanasiadou Anastasia , Anagnostopoulos Achilles 
Published: October 2019

Abstract
Abstract 5025

Background:
Data on outcomes of patients (pts) with myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN), especially MDS/MPN-unclassified (MDS/MPN-U), are scarce.

Patients/methods:
We retrospectively studied pts followed in our center, with MDS/MPN according to WHO 2008 criteria. Because of overlap characteristics of MPN and MDS, pts with systemic mastocytosis associated with MDS (SM/MDS) were also included. Pts with previous MDS or MPN were excluded. Response and disease progression were defined according to IWG 2006 criteria.

Results:
Twenty-five pts with MDS/MPN were included. Median age was 70 y (range 19–79). Male/female ratio was 1.77/1. Diagnosis was CMML-1 N=7, CMML-2 N=7, JMML N=1, MDS/MPN-U N=8, systemic mastocytosis (SM)/MDS N=2, with one additional pt with CMML subsequently developing SM. At diagnosis, median WBC count was 18.8 G/L (range 3–120), ANC 15.5 G/L (0.6–70), monocytes 1.9 G/L (0.1–16), left shift 16% (0–28), Hb 11.2 g/dL (6–17), platelets 99 G/L (10–680), peripheral and bone marrow (BM) blasts 5% (0–17) and 7% (2–19), respectively (resp.). 25% of pts had platelets count ≥400 G/L. Splenomegaly, B-symptoms and BM fibrosis were present in 23%, 57% and 27% of pts, resp. Karyotype was fav, int and unfav in 55%, 36% and 9% of pts, with −7, +8, del(12)(p11), del(12)(q14;q21), +10, +21, and previously unreported t(9;12)(q13;q13) in 3, 6, and 1 pt each, resp., while +21 and i(17)(q10) appeared during disease progression other than AML transformation. IPSS was low/int-1 and int-2/high in 50% and 50% of pts, resp. JAK2 V617F and CKIT D816V mutations were detected in 2/6 pts and 2/2 SM/MDS pts, resp. 70% and 29% of pts were transfused at diagnosis with PRBC and platelets, resp.
Treatment included erythropoiesis stimulating agents (ESAs), low dose chemotherapy, intensive chemotherapy (IC) and azacitidine (AZA) in 40%, 36%, 16% and 48% of pts resp. Response rate to ESAs, IC and AZA was 60%, 14% and 14% resp. Response rate to AZA in CMML-1 pts was 33%. Dasatinib yielded no response in 1 SM/MDS pt with CKIT D816V.
3-year cumulative incidence of AML and median overall survival (OS) in pts with CMML-1, CMML-2 and MDS/MPN-U were 20%, 40% and 0 (P=0.059) and 39, 8, and 20 mo (P=0.50), resp. The pt with JMML died from AML transformation 3 months after diagnosis. 2/3 pts with SM/MDS died from disease progression w/o AML at a median of 10 mo after diagnosis. Median survival after disease progression other than AML transformation was 35, 15 and 14 mo in pts with CMML-1, CMML-2 and MDS/MPN-U, resp. (P=0.88). Cause of death was disease progression other than AML, AML transformation and unrelated to disease in 50%, 50%, and 0 and 80%, 0 and 20% of cases in CMML and MDS/MPN-U, resp. (P=0.10). Percentage of circulating blasts ≥5% was the only independent factor affecting risk of AML transformation in the overall population (P=0.0004). Diagnosis other than CMML-1, WBC ≥30 G/L, % of circulating blasts ≥5% and IPSS high/int-2 were associated with worse survival in univariate analysis (P=0.06, 0.03, 0.04 and 0.08, resp.). No predictive factor of OS was found in multivariate analysis.

Conclusion:
MDS/MPN are heterogeneous disorders with respect to disease progression and AML transformation. MDS/MPN-U tended to differ from CMML-1 by shorter survival after disease progression other than AML, and from CMML-2 by lower risk of AML transformation. Mortality of pts with MDS/MPN-U was mainly attributed to disease progression without AML transformation. Alternatively to hypomethylating agents, therapeutic options in pts with MDS/MPN-U could include JAK2 inhibitors.

Disclosures:
No relevant conflicts of interest to declare.