Azacitidine (AZA) has proven effective (response rate: 60-80%) in myelodysplastic syndromes (MDS). The currently approved AZA regimen (AZA 7) is 75 mg/sqm/die subcutaneously (SC) for 7 days every 28 days. Recently a different AZA dosing schedule (AZA 5-2-5: 50 mg/m2/d subcutaneously for 5 days, followed by 2 days no treatment, then 50 mg/m2/d for 5 days), which avoids week-end dosing, has shown to induce therapeutic responses consistent with the currently approved schedule, in a population of mainly low risk pts (Lyons, 2009). These data prompted us to investigate the therapeutic effect of the AZA 5-2-5 regimen in high risk MDS pts (IPSS risk: high or intermediate-2). From September 2004, in our Institution, 28 high risk MDS pts. were treated with 2 different AZA dosing schedules. Group 1 (9 pts, 8 males, median age: 68, range 60-84 yrs) received the AZA 7 regimen, while group 2 (19 pts, 13 males, median age: 69, range 37-81 yrs) received the 5-2-5 AZA regimen. Moreover, as our group (Follo, 2009) demonstrated that phosphoinositide-phospholipase C (PI-PLC) beta1 may represent a target for AZA, we quantified the degree of PI-PLCbeta1 methylation and gene expression before and during AZA administration in both groups. Pts of group 1 received a median number of 12 (1-59) AZA cycles. Among the 8 evaluable pts (i.e.: at least 6 cycles) 5 (62.5%) showed a favourable response, following IWG criteria (Cheson, 2006): 1 Complete Remission (CR), 1 Partial Remission (PR) and 3 Hematologic Improvement (HI). 3 pts died because of evolution into Acute Myeloid Leukemia (AML), and 4 pts for other causes. One pts, still alive and under imatinib therapy, developed Ph1+ Chronic Myeloid Leukemia (CML) after 59 courses of AZA. Mean follow-up of group 1 pts: 31 (13-79) months. Pts of group 2 received a median number of 8 (1-17) AZA cycles. Among the 15 evaluable pts, 13 (86.6%) showed a favourable response: 5 CR (33.3%) and 8 HI. 3 pts died because of evolution into AML, and 2 for other causes. 2 pts underwent allogeneic stem cell transplantation, both after achieving CR. 12 pts are alive, 9 of them still under AZA treatment. Mean follow-up of group 2 pts: 14 (1-35) months. PI-PLCbeta1 methylation and gene expression appeared to be related to the therapeutic response, but not to the dose schedule. Our results, although larger studies are required, seem to confirm the effectiveness of the more convenient AZA 5-2-5 regimen, even in high risk MDS.

AZACITIDINE FOR HIGH RISK MYELODYSPLASTIC SYNDROMES. RETROSPECTIVE EVALUATION OF TWO DIFFERENT DOSING SCHEDULES

FINELLI, CARLO;FOLLO, MATILDE YUNG;PAOLINI, STEFANIA;PAPAYANNIDIS, CRISTINA;MONGIORGI, SARA;Parisi S;MANZOLI, LUCIA;MARTINELLI, GIOVANNI;COCCO, LUCIO ILDEBRANDO;BACCARANI, MICHELE
2011

Abstract

Azacitidine (AZA) has proven effective (response rate: 60-80%) in myelodysplastic syndromes (MDS). The currently approved AZA regimen (AZA 7) is 75 mg/sqm/die subcutaneously (SC) for 7 days every 28 days. Recently a different AZA dosing schedule (AZA 5-2-5: 50 mg/m2/d subcutaneously for 5 days, followed by 2 days no treatment, then 50 mg/m2/d for 5 days), which avoids week-end dosing, has shown to induce therapeutic responses consistent with the currently approved schedule, in a population of mainly low risk pts (Lyons, 2009). These data prompted us to investigate the therapeutic effect of the AZA 5-2-5 regimen in high risk MDS pts (IPSS risk: high or intermediate-2). From September 2004, in our Institution, 28 high risk MDS pts. were treated with 2 different AZA dosing schedules. Group 1 (9 pts, 8 males, median age: 68, range 60-84 yrs) received the AZA 7 regimen, while group 2 (19 pts, 13 males, median age: 69, range 37-81 yrs) received the 5-2-5 AZA regimen. Moreover, as our group (Follo, 2009) demonstrated that phosphoinositide-phospholipase C (PI-PLC) beta1 may represent a target for AZA, we quantified the degree of PI-PLCbeta1 methylation and gene expression before and during AZA administration in both groups. Pts of group 1 received a median number of 12 (1-59) AZA cycles. Among the 8 evaluable pts (i.e.: at least 6 cycles) 5 (62.5%) showed a favourable response, following IWG criteria (Cheson, 2006): 1 Complete Remission (CR), 1 Partial Remission (PR) and 3 Hematologic Improvement (HI). 3 pts died because of evolution into Acute Myeloid Leukemia (AML), and 4 pts for other causes. One pts, still alive and under imatinib therapy, developed Ph1+ Chronic Myeloid Leukemia (CML) after 59 courses of AZA. Mean follow-up of group 1 pts: 31 (13-79) months. Pts of group 2 received a median number of 8 (1-17) AZA cycles. Among the 15 evaluable pts, 13 (86.6%) showed a favourable response: 5 CR (33.3%) and 8 HI. 3 pts died because of evolution into AML, and 2 for other causes. 2 pts underwent allogeneic stem cell transplantation, both after achieving CR. 12 pts are alive, 9 of them still under AZA treatment. Mean follow-up of group 2 pts: 14 (1-35) months. PI-PLCbeta1 methylation and gene expression appeared to be related to the therapeutic response, but not to the dose schedule. Our results, although larger studies are required, seem to confirm the effectiveness of the more convenient AZA 5-2-5 regimen, even in high risk MDS.
HAEMATOLOGICA
163
163
Finelli C; Clissa C; Follo MY; Curti A;Paolini S; Papayannidis C; Mongiorgi S; Parisi S; Bosi C; Manzoli L; Martinelli G; Cocco L; Baccarani M
File in questo prodotto:
Eventuali allegati, non sono esposti

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/396730
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact