Introduction. Erytropoiesis-stimulating agents (ESAs) are effective in 20-30% of patients (pts) with Myelodysplastic Syndromes (MDS), but response rates are higher when pts are selected on the basis of clinical and hematologic parameters: baseline serum erythropoietin (EPO) level <200-500 IU/L, , <10% marrow blasts, IPSS risk low or INT-1, shorter interval between diagnosis and treatment. The median duration of the response to ESAs is approximately 2 yrs, and a significantly longer response duration is associated with: major response (following IWG criteria), < 5% marrow blasts, absence of multilineage dysplasia (Jadersten, 2005; Park, 2008). These data prompted us to retrospectively analyse our MDS pts treated with ESAs, in order to enucleate long-responder pts (duration of response ≥20 months). METHODS. From October 2001, in our Institution, 69 MDS pts (50 males), median age: 78 (42-92) yrs, with Hb level <10 g/dL, IPSS risk low or INT-1 , and baseline serum EPO < 500 mIU/mL, were treated with epoetin alpha (EPO), at a starting dose of 40-80.000 IU s.c. per week (once or twice weekly), for a minimum of 12 weeks. Hematologic response was defined according to revised IWG criteria (Cheson, 2006). In a subgroup of pts we also studied the expression of several genes involved in inositide signaling. RESULTS. 34 pts (49.3%) showed a prolonged hematologic response (≥20 months). Pretreatment clinical and haematologic features of long-responders: sex (M/F): 21/13; median age: 77 (42-90) yrs; WHO diagnosis: RA: 22 pts; RARS: 6 pts; RCMD: 1 pt; RAEB-1: 5 pts.; IPSS risk: low . 25 pts, INT-1: 9 pts; WPSS risk: very low: 16 pts (47.1%), low: 12 pts (35.3%); INT: 3 pts (8.8%); high: 3 pts (8.8%); IPSS cytogenetic risk: low: 33 pts; INT.: 1 pt ; pre-treatment transfusions: 11 pts (32.4%); high pre-treatment transfusion need ( >4 units/8 weeks): 6 pts (17.6%); long interval from diagnosis to the start of EPO ( > 6 months) : 20 pts (58.8%). Starting weekly EPO dose: 80.000 U: 20 pts; 40.000 U: 14 pts. Outcome: median time to response: 8 (4-32) weeks; type of response: Complete Response (CR): 14 pts (44.1%); Haematologic Improvement (HI): 19 pts (55.1%); median duration of response: 47.5 (20-125) months; 15 pts (44.1%) were able to shift to a lower maintenance dose. Relapse occurred in 7 pts (20.6%) ( in 2 pts because of disease progression) after a median of 48 months. 24 pts are still alive, 5 pts died (none of them for AML), and 5 pts were lost at follow-up. Median survival (from the start of EPO): 51 (22-128) months. 13 pts show a shorter response but are still on treatment , 12 pts showed a short-lived reponse (< 20 months), and 10 pts did not respond to EPO. Conclusions. Our data show that, although in MDS the duration of response to EPO is limited, a substantial fraction of pts may show a long-lasting response, and that, unexpectedly, some of them may show unfavourable pre-treatment prognostic features (WPSS risk, high transfusion need).
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS) IN MYELODYSPLASTIC SYNDROMES: RETROSPECTIVE EVALUATION OF LONG-RESPONDER PATIENTS
FINELLI, CARLO;FOLLO, MATILDE YUNG;PAOLINI, STEFANIA;PAPAYANNIDIS, CRISTINA;MONGIORGI, SARA;Parisi S;MARTINELLI, GIOVANNI;COCCO, LUCIO ILDEBRANDO;BACCARANI, MICHELE
2012
Abstract
Introduction. Erytropoiesis-stimulating agents (ESAs) are effective in 20-30% of patients (pts) with Myelodysplastic Syndromes (MDS), but response rates are higher when pts are selected on the basis of clinical and hematologic parameters: baseline serum erythropoietin (EPO) level <200-500 IU/L, , <10% marrow blasts, IPSS risk low or INT-1, shorter interval between diagnosis and treatment. The median duration of the response to ESAs is approximately 2 yrs, and a significantly longer response duration is associated with: major response (following IWG criteria), < 5% marrow blasts, absence of multilineage dysplasia (Jadersten, 2005; Park, 2008). These data prompted us to retrospectively analyse our MDS pts treated with ESAs, in order to enucleate long-responder pts (duration of response ≥20 months). METHODS. From October 2001, in our Institution, 69 MDS pts (50 males), median age: 78 (42-92) yrs, with Hb level <10 g/dL, IPSS risk low or INT-1 , and baseline serum EPO < 500 mIU/mL, were treated with epoetin alpha (EPO), at a starting dose of 40-80.000 IU s.c. per week (once or twice weekly), for a minimum of 12 weeks. Hematologic response was defined according to revised IWG criteria (Cheson, 2006). In a subgroup of pts we also studied the expression of several genes involved in inositide signaling. RESULTS. 34 pts (49.3%) showed a prolonged hematologic response (≥20 months). Pretreatment clinical and haematologic features of long-responders: sex (M/F): 21/13; median age: 77 (42-90) yrs; WHO diagnosis: RA: 22 pts; RARS: 6 pts; RCMD: 1 pt; RAEB-1: 5 pts.; IPSS risk: low . 25 pts, INT-1: 9 pts; WPSS risk: very low: 16 pts (47.1%), low: 12 pts (35.3%); INT: 3 pts (8.8%); high: 3 pts (8.8%); IPSS cytogenetic risk: low: 33 pts; INT.: 1 pt ; pre-treatment transfusions: 11 pts (32.4%); high pre-treatment transfusion need ( >4 units/8 weeks): 6 pts (17.6%); long interval from diagnosis to the start of EPO ( > 6 months) : 20 pts (58.8%). Starting weekly EPO dose: 80.000 U: 20 pts; 40.000 U: 14 pts. Outcome: median time to response: 8 (4-32) weeks; type of response: Complete Response (CR): 14 pts (44.1%); Haematologic Improvement (HI): 19 pts (55.1%); median duration of response: 47.5 (20-125) months; 15 pts (44.1%) were able to shift to a lower maintenance dose. Relapse occurred in 7 pts (20.6%) ( in 2 pts because of disease progression) after a median of 48 months. 24 pts are still alive, 5 pts died (none of them for AML), and 5 pts were lost at follow-up. Median survival (from the start of EPO): 51 (22-128) months. 13 pts show a shorter response but are still on treatment , 12 pts showed a short-lived reponse (< 20 months), and 10 pts did not respond to EPO. Conclusions. Our data show that, although in MDS the duration of response to EPO is limited, a substantial fraction of pts may show a long-lasting response, and that, unexpectedly, some of them may show unfavourable pre-treatment prognostic features (WPSS risk, high transfusion need).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
