Introduction. Azacitidine (AZA) has proven effective in myelodysplastic
syndromes (MDS). The duration of haematological response is limited
(median 13.6 months) (Fenaux, 2009), although some patients (pts)
show a prolonged response. These data prompted us to retrospectively
analyse our MDS pts treated with AZA, in order to enucleate longresponder
pts (duration of response 6520 months). METHODS. From
September 2004, in our Institution, 52 MDS pts (40 males), median age:
70 (37-85) yrs, were treated with AZA, following 4 different treatment
regimens: 9 pts received the AZA 7 regimen (AZA 7: 75 mg/sqm/die SC
for 7 days/28 days); 6 pts received the combination of AZA 7 with valproic
acid and all-trans-retinoic acid ; while 25 and 12 pts respectively
received the alternative regimens AZA 5-2-5 and AZA 5 (Lyons, JCO
2009). 37 pts (71%) showed a IPSS high-risk MDS, while 15 pts (29%)
with IPSS low-risk MDS received AZA because of refractoriness or ineligibility
to erythropoietin, or secondary MDS. Moreover, as our group
(Follo, 2009) demonstrated that phosphoinositide-phospholipase C (PIPLC)
beta1 may represent a target for AZA, we quantified the degree
of PI-PLCbeta1 methylation and gene expression before and during AZA administration. RESULTS. 9 pts (17.3%) showed a prolonged
hematologic response ( 65 20 months). Pre-treatment clinical and haematologic
features of long-responders: sex (M/F): 4/5; median age: 69 (52-
84); WHO: RCMD-RS: 1 pt; RAEB-1: 1 pt; RAEB-2: 7 pts; IPSS risk:
low: 1 pt; int-1: 2 pts; int-2: 5 pts; high: 1 pt; IPSS cytogenetic risk: low:
7 pts; interm: 1 pt; high: 1 pt; ECOG: 0-1: 8 pts, 65 2: 1 pt; transfusion
need (N\ub0 U)/8 weeks: < 4 : 4 pts; 65 4 : 5 pts; time from diagnosis
(months): < 6 : 6 pts; 65 6 : 3 pts. Therapeutic regimen: AZA 7: 3 pts; AZA
5: 3 pts; AZA 5-2-5: 3 pts. Therapeutic response: median number of
cycles: 19 (8-59); median time to 1st response: 3 (2-6) months; type of
response: Complete Remission (CR): 3 pts; Hematologic Improvement
(HI): 6 pts; cytogenetic remission: 1 pt; median duration of response: 30
(24-66) months; doubling of platelet count after 1st cycle: 4 pts; toxicity
(grade > 2): 3 pts; 4 pts are still maintaining hematologic response,
3 pts are still alive but discontinued treatment because of disease progression,
and 2 pts died (1 for AML and 1 for cachexy). Median survival
(from the start of AZA): 38 (25-103) months. All the pts showed an
increase in PI-PLCbeta1 expression, that was maintained along with
the hematologic response. 15 pts (28.8%) showed a short-lived reponse
(< 20 months), 5 pts (9.6%) show a shorter response but are still on
treatment, 2 pts underwent allogeneic transplantation after 5 and 10
months. 7 pts (13.4%) are not evaluable for response (< 6 cycles), and
14 pts (26.9%) did not respond to AZA. Conclusions. Our data show that
a limited but significant fraction of MDS pts show a long-lasting hematologic and molecular response to AZA
