ALBERT

Description: Background: EPO and its derivative darbepoietin alfa (DAR) are important treatments of anemia in lower risk MDS. Prognostic factors of response and of its duration have been recently updated (Blood, 2005, 106, 803–11) and we reanalyzed them in a large series of patients (pts) treated in France and Belgium. Patients: 419 MDS pts were treated with EPO (≥30000UI/wk for at least 12 wks) or DAR (300μg/wk)± GCSF in 25 GFM centers between 1998 and 2006 (160 prospectively analyzed in 3 consecutive trials, and 259 retrospectively analyzed). Median follow-up was 54 months, median age: 73.5 years. WHO classification: RA (14%), RCMD (16%), 5q- syndrome (4%), RARS (21%) RCMD-RS (13%), RAEB-1 (22%), RAEB-2 (6%), and also 4%CMML (FAB); karyotype: 64% FAV, 16% INT, and 4% UNFAV (16% failure or not done). IPSS: 34% LOW, 40% INT-1, 8% INT-2, 2% HIGH (16% unavailable). 185, 126, 80 and 28 pts received EPO alone (alfa or beta), DAR, EPO+G and DAR+G respectively. Median pre-treatment EPO level was 76 UI/l (only 7% pts〉500 UI/l). All pts had Hb2 RBC units/month). Results: 63% pts responded (IWG criteria: 43%HI-E major and 20% HI-E minor), including 57%, 63%, 57%, 66%, 63% with EPO alfa alone, beta alone, EPO+G, DAR alone, DAR+G response (p=ns). Median response duration was 20 mos (range 3–74 mos), 25 and 14 mos for major and minor responses (p= 0.001). Relapse was associated with treatment discontinuation (45%), progression to higher grade MDS (12%) or AML (13%), but without evident cause in 30% cases. In univariate analysis, significantly higher response rates were observed in pts with

Description: Background: RBC transfusions remain a mainstay in the treatment in MDS, but their characteristics in a large MDS population have not been reported in detail. Indications of iron chelation therapy (CT) in those patients, are based on consensus (Gattermann Hematology/Oncology Clinics 2005;19:supp1 ) but have not been reported in a large MDS cohort. In addition, a positive effect of desferioxamine (DFO) therapy on hematopoiesis has been reported in a small group of MDS (Jensen BJH, 1996;94:288). Methods: We analyzed the hematological characteristics, RBC transfusion requirement and iron CT in MDS patients referred for RBC transfusion in 18 French centers between May 15 and June 15, 2005. Results: 170 pts were included in the survey, median age 75 (14–95); M/F ratio 1.37; median time from diagnosis was 43 months (1 month to 17.5 years); WHO: pure RA 8.8%, pure RARS 18%, RCMD 3.5%, RCMD-RS 3%, RAEB I 16.5%, RAEB II 5.3%, 5q- syndrome 7%, CMML 4.7%, unclassified12.6%. Karyotype: fav (12%), int (37%), unfav ( 23%), failure or not done ( 28%). IPSS: low 39%, Int1 45%, Int2 13.5%, high 2.5%, unavailable 28%. Median serum ferritin (SF) level at diagnosis was 562ng/ml (9–2500). Median number of RBC units transfused since diagnosis was 49, mean 80 (2–610) and did not differ statistically according to WHO or IPSS. 81% of patients had received 〉 21 RBC units. Median number of RBC units transfused at initiation of CT was 21 (2–151). 68/170 pts ( 40 %) had received CT during the disease course including: DFO continuous s/c (8h) (40mg/kg/d, 3 to 5d/ week) n = 37, DFO s/c bolus (2 to 8g/week) n = 14, DFO IV (50 to 100mg/kg/d once after each RBC transfusion) n=7, deferiprone alone (30 to 75 mg/kg/d) n=4. Deferiprone + DFO s/c n=6. Median SF level was 1492ng/ml at the start of iron CT (436–6572). 50/68 pts were still on iron CT at the time of the survey after 2 to 114 months. Median SF level at the time of survey was 1828ng/ml (not statistically different from pre CT level). No positive effects were observed on hematopoiesis even in pts chelated for prolonged periods. 18/68 patients stopped CT (all were on DFO therapy) due to over efficacy n= 1, local complications n = 7, patient decision n=10 ). Median duration of treatment was 9 months (1–78) and median level of SF 3227ng/ml at the time of survey in those 18pts. For the 102/170 pts who did not receive CT, main reasons given by physicians were: older age 33% (median age in this group was indeed 82); cumbersome treatment 12%; high IPSS 8% (all cases had indeed IPSS〉=1.5); low transfusion requirement 8% (median=11 RBC units transfused in this group); other reasons 5% (refusal, skin lesions), no reason given 34%. By comparison to non chelated patients, chelated patients had significantly higher number of RBC units transfused (mean 115 vs 55) (p

Description: We conducted a phase II trial of thalidomide in patients with low risk MDS issued from the GFM. 82 patients were included from january 2003 to june 2004: 38 RA, 19 RARS, 21 RAEB

Description: We performed a randomized study of hydroxyurea (HY) versus VP16 in advanced chronic myelomonocytic leukemia (CMML) patients with CMML (according to French-American-British group criteria) and either documented visceral involvement (excluding liver and spleen infiltration) or at least 2 of the following: (1) neutrophils 〉 16 x 10(9)/I (2) Hemoglobin 〈 10 g/dL (3) platelets 〈 100 x 10(9)/L (4) marrow blasts 〉 5% (5) spleen 〉 5 cm below costal margin were eligible for this trial. Initial dosage was 1 g/d for HY and 150 mg/week for VP16, orally (doubled in case of visceral involvement). Doses were scheduled to be escalated up to HY 4 g/d and VP16 600 mg/week in the absence of response, and finally adjusted to maintain white blood cells (WBCs) between 5 and 10 x 10(9)/L. Crossing over was scheduled only in case of life threatening visceral involvement or major progression. The major endpoint of the study was survival. The study was closed on first interim analysis that showed a superiority of HY over VP16, after inclusion of 105 pts (HY arm: 53, VP16 arm: 52). Results of the second interim analysis, performed 7 months later, are presented here. Median age was 71 (range 38 to 91), median WBC count 20.10(9)/L (range 10 to 187). Thirteen pts had visceral involvement (3 serous effusions, 8 cutaneous infiltrations, 1 kidney, 1 bone infiltrations). Initial characteristics were similar in the HY and VP16 groups. Median follow up was 11 months in both groups (range 1 to 43+). Response to treatment was seen in 60% of the pts in the HY group, versus 36%, respectively, in the VP16 group (P = .02). Time to response was significantly shorter in the HY group (2.1 v 3.5 months, in the VP16 group, P = .003) and response duration was significantly longer in the HY group (median 24 v 9 months, in the VP16 group, P = .0004). The response rate of patients with visceral involvement was 3 out of 7 in the VP16 arm versus 5 out of 6 in the HY group. Three of the 10 pts crossed over from HY to VP16 responded as compared to 6 pts of the 11 pts crossed over from VP16 to HY. HY yielded better response on leukocytosis (P = .002). The effect on splenomegaly platelets, on hemoglobin level and transfusion requirement was similar in the 2 treatment groups. A significantly higher incidence of alopecia was noted in the VP16 arm (20% v 3%, P = .03). Fourteen (27%) and 20 (38%) patients in the HY and the VP16 group respectively, progressed to acute myeloid leukemia (difference NS). Twenty five (53%) and 44 (83%) patients in the HY and the VP16 group, respectively, had died (P = .002). Median actuarial survival was 20 months in the HY arm, versus 9 months in the VP16 arm (P 〈 10(-4)). Main factors associated with poor survival were allocation to the VP16 arm, “unfavorable” karyotype (ie, monosomy 7 or complex abnormalities) and anemia. In the HY group, unfavorable karyotype (P = .006), and low hemoglobin level (P = .004) were significantly associated with low response rates. Prognostic factors for poor survival in the HY group were also unfavorable karyotype (P = .001), and low hemoglobin level (P 〈 10(-4). In conclusion, we found that HY gave higher response rates and better survival than VP16 in advanced CMML. However, even with HY responses were only partial and survival was generally poor. This stresses the need for new agents in the treatment of CMML, that will have to be compared with HY in future randomized studies.