Impact Of Myelofibrosis (MF) In MDS Treated With Azacitidine (AZA). A Single Center Study

Bone marrow fibrosis is observed in 10-20% of MD, and is a poor prognostic factor, both in lower and higher risk MDS (Della Porta, JCO 2009). AZA, the current reference treatment for higher risk MDS, approved in EU for patients with up to 30% bone marrow blasts not candidates to intensive chemotherapy (IC) or allogeneic SCT, gives 50-60% responses and improves OS in higher-risk MDS but its role in MDS with myelofibrosis remains unknown.

Between 2004 and 2012, we treated at our center 172 consecutive MDS patients (pts) including FAB RAEB-T / WHO AML with 20-30% blasts, with AZA (75 mg/m2/d x7 d every 4 weeks, for a median of 6 cycles). We assessed in those patients the impact of myelofibrosis (MF), evaluated on bone marrow trephine biopsy and graded according to the European consensus on grading bone marrow fibrosis.

Median age of the 172 pts was 73 years and 67% were males. According to WHO classification, 1 had del(5q) syndrome, 4 RARS/RCMD-RS, 24 RCMD, 37 RAEB-1, 54 RAEB-2, 29 AML (20-30% blasts), 17 CMML and 6 MDS unclassified. Median Hb level, WBC, platelet count and marrow blast count were 9.4 g/dl (range 3.5-15), 1.6 G/L (0-58), 75G/l (8-1080) and 12%(1-29), respectively. IPSS was low, Int-1, Int-2, High and a failure in 1(>1%), 29(17%), 65 (38%), 59 (34%) and 18 (11%) patients, respectively. Twenty-three pts (13%) had grade 2-3 myelofibrosis (MF). Patients with MF were younger (median 68 vs. 74 years, p= 0.04), but had similar hematological characteristics: hemoglobin (median 9 vs. 9.45g/dl, p= 0.69); WBC (2.2 vs. 1.6 G/l, p= 0.48) Platelet (47 vs 77 G/l,p= 0.43) and bone marrow blast (10 vs. 12%, p=0.67). IPSS was int 1, int 2, high and a failure in 4, 7, 6 and 6 patients respectively without difference compared to patients without fibrosis. Cytogenetics was complex in 8, del(20q) +/- 1 additional abn in 5 patients, normal in 4 patients, failed in 6 patients (but with trisomy 8 and monosomy 7, resp, detected in 2 patients by FISH analysis). Overall, 73 (42%) patients achieved a response according to IWG2006 criteria, including 31 (18%) CR. The response rate and CR rate were 52% and 17% respectively in pts with MF, compared to 44% and 20% in pts without MF (p= 0.507 and p=1.00, respectively). With a median follow-up of 6.5 yr, median OS was 12 months in pts with MF, compared to 16 months in pts without MF (p=0.45).

In this MDS series, presence of MF was not associated with specific features (but blasts were often counted on marrow aspirates, with a possible underestimate in case of MF). Response to AZA and survival after AZA onset did not significantly differ based on the presence of MF.

No relevant conflicts of interest to declare.