Azacitidine (AZA) has proven effective in Myelodysplastic Syndromes (MDS), and the currently approved AZA regimen is 75 mg/sqm/die subcutaneously for 7 days every 28 days. Subsequently, other alternative and more convenient AZA dosing regimens have shown to be effective, in terms of hematologic responses (Lyons, 2009). From September 2004, in our Institution, 57 MDS patients (pts) (43 males), with a median age of 70 (37-84) yrs, were treated with AZA, following 4 different treatment regimens. Group 1 (10 pts), received the currently approved regimen (AZA 7). Group 2 (6 pts), received the AZA 7 regimen with valproic acid and all-trans-retinoic acid. Group 3 (29 pts) received the AZA 5-2-5 regimen: 50 mg/sqm/die SC for 10 days/28 days. Group 4 (12 pts) received the AZA 5 regimen: 75 mg/sqm/die SC for 5 days/28 days. Moreover, we quantified the degree of phosphoinositide-phospholipase C (PI-PLC) beta1 methylation and gene expression before and during AZA administration. At AZA onset, IPSS risk was: low: 3 pts; intermediate-1: 12 pts; intermediate-2: 33 pts; high: 9 pts. R-IPSS risk was: very low: 1 pt; low: 3 pts; intermediate: 7 pts; high: 10 pts; very high: 36 pts. WPSS risk was low: 3 pts; intermediate: 5 pts; high: 9 pts; very high: 40 pts. 9 pts had therapy-related MDS. ECOG-PS was poor (≥2) in 15 pts. Transfusion need was high (≥4 RBC units/8 weeks) in 34 pts. 6 pts presented circulating blasts. Following Itzykson’s AZA prognostic scoring system, the risk was low in 7 pts (12.3 %), intermediate in 48 pts (84.1 %), and high in 2 pts (3.6 %). The pts received a median of 8 cycles of AZA (range: 1-59). 50 pts were considered evaluable for response (at least 6 cycles): 34/50 pts (68%) showed a favourable response following IWG criteria (Cheson, 2006): complete remission (CR) in 7 pts (14% %), hematologic improvement (HI): 27 pts (54%). The median duration of response was 12 (range: 1-88) months. Group 1: 5 responders (62.5%) (1 CR and 4 HI); Group 2: 3 responders (50%) (3 HI); Group 3: 19 responders (73.1%) (5 CR, 14 HI); Group 4: 7 responders (70%) (2 CR, 5 HI). A significant toxicity (grade >2) was observed in 23 (40.4 %) pts. 37 pts died, 13 for AML, 9 for infection, 17 for other causes. Median OS from the start of AZA was 18 (range: 5-108) months. The detection of an increase in PIPLCbeta1 gene expression within the first three cycles of AZA therapy was significantly associated with a better clinical outcome and a longer hematologic response.

AZACITIDINE IN HIGH AND LOW RISK MYELODYSPLASTIC SYNDROMES: RETROSPECTIVE EVALUATION OF 57 PATIENTS TREATED WITH 4 DIFFERENT THERAPEUTIC REGIMENS

FINELLI, CARLO;FOLLO, MATILDE YUNG;PAOLINI, STEFANIA;PAPAYANNIDIS, CRISTINA;MONGIORGI, SARA;Parisi S;MANZOLI, LUCIA;MARTINELLI, GIOVANNI;COCCO, LUCIO ILDEBRANDO;CAVO, MICHELE
2013

Abstract

Azacitidine (AZA) has proven effective in Myelodysplastic Syndromes (MDS), and the currently approved AZA regimen is 75 mg/sqm/die subcutaneously for 7 days every 28 days. Subsequently, other alternative and more convenient AZA dosing regimens have shown to be effective, in terms of hematologic responses (Lyons, 2009). From September 2004, in our Institution, 57 MDS patients (pts) (43 males), with a median age of 70 (37-84) yrs, were treated with AZA, following 4 different treatment regimens. Group 1 (10 pts), received the currently approved regimen (AZA 7). Group 2 (6 pts), received the AZA 7 regimen with valproic acid and all-trans-retinoic acid. Group 3 (29 pts) received the AZA 5-2-5 regimen: 50 mg/sqm/die SC for 10 days/28 days. Group 4 (12 pts) received the AZA 5 regimen: 75 mg/sqm/die SC for 5 days/28 days. Moreover, we quantified the degree of phosphoinositide-phospholipase C (PI-PLC) beta1 methylation and gene expression before and during AZA administration. At AZA onset, IPSS risk was: low: 3 pts; intermediate-1: 12 pts; intermediate-2: 33 pts; high: 9 pts. R-IPSS risk was: very low: 1 pt; low: 3 pts; intermediate: 7 pts; high: 10 pts; very high: 36 pts. WPSS risk was low: 3 pts; intermediate: 5 pts; high: 9 pts; very high: 40 pts. 9 pts had therapy-related MDS. ECOG-PS was poor (≥2) in 15 pts. Transfusion need was high (≥4 RBC units/8 weeks) in 34 pts. 6 pts presented circulating blasts. Following Itzykson’s AZA prognostic scoring system, the risk was low in 7 pts (12.3 %), intermediate in 48 pts (84.1 %), and high in 2 pts (3.6 %). The pts received a median of 8 cycles of AZA (range: 1-59). 50 pts were considered evaluable for response (at least 6 cycles): 34/50 pts (68%) showed a favourable response following IWG criteria (Cheson, 2006): complete remission (CR) in 7 pts (14% %), hematologic improvement (HI): 27 pts (54%). The median duration of response was 12 (range: 1-88) months. Group 1: 5 responders (62.5%) (1 CR and 4 HI); Group 2: 3 responders (50%) (3 HI); Group 3: 19 responders (73.1%) (5 CR, 14 HI); Group 4: 7 responders (70%) (2 CR, 5 HI). A significant toxicity (grade >2) was observed in 23 (40.4 %) pts. 37 pts died, 13 for AML, 9 for infection, 17 for other causes. Median OS from the start of AZA was 18 (range: 5-108) months. The detection of an increase in PIPLCbeta1 gene expression within the first three cycles of AZA therapy was significantly associated with a better clinical outcome and a longer hematologic response.
HAEMATOLOGICA
200
200
Clissa C;Finelli C;Follo MY; Stanzani M; Curti A; Paolini S; Papayannidis C; Mongiorgi S; Parisi S; Abbenante MC; Bosi C; Manzoli L; Martinelli G; Cocco L; Cavo M
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/396800
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