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  • 1
    Online Resource
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    Elsevier BV ; 2017
    In:  European Journal of Internal Medicine Vol. 46 ( 2017-12), p. e15-e16
    In: European Journal of Internal Medicine, Elsevier BV, Vol. 46 ( 2017-12), p. e15-e16
    Type of Medium: Online Resource
    ISSN: 0953-6205
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
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  • 2
    In: Autoimmunity Reviews, Elsevier BV, Vol. 16, No. 9 ( 2017-09), p. 903-910
    Type of Medium: Online Resource
    ISSN: 1568-9972
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2099325-0
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  • 3
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 422-422
    Abstract: Abstract 422 Background: The IPSS published in 1997, based on cytogenetics, marrow blast % and the number of cytopenias, has played a major role in prognosis assessment in MDS. A provisional revised IPSS had been presented in 2011, which in our experience brought limited additional prognostic value for outcome of AZA treatment (Lamarque, ASH 2011). A final IPSS-R has now been published (Greenberg, Blood 2012), using the same parameters but 5 rather than 3 cytogenetic subgroups (Schanz et al, JCO, 2011), new cut off values for cytopenias and bone marrow blast % and different weighing of parameters. It appears to refine IPSS prognostic value but, like the original IPSS, was established in pts who had received no disease modifying drugs. We assessed the prognostic value of IPSS-R in 264 higher risk MDS treated with AZA, a drug with a survival impact in those pts. Methods: Between Sept 2004 and Jan 2009, before drug approval in EU, we enrolled 282 IPSS high and int 2 (higher) risk MDS in a compassionate patient named program of AZA and established in this cohort a prognostic scoring system (“AZA predictive score” based on Performance status (PS), cytogenetics, presence of circulating blasts, and RBC transfusion dependency) (Itzykson, Blood, 2011). We took advantage of this cohort to evaluate the prognostic impact of IPSS-R in higher risk MDS treated with AZA. Results: Median age was 71 years. WHO diagnosis: 4% RA, RARS or RCMD, 20% RAEB-1, 54%RAEB-2, 22% RAEB-t/AML. Cytogenetics could be reclassified using IPSS-R cytogenetic groups (Shanz, JCO 2011) in 265 pts, in: 1% very good, 37% good, 18% int, 12% poor and 32% very poor. 18%, 48% and 34% pts had Hb 〈 8g/dl, between 8 and 10 and 〉 10 g/dl, respectively. 43%, 32% and 25% had baseline platelet count 〈 50 G/l between 50–100 and 〉 100 G/L, respectively. ANC was 〈 0.8 G/l in 45% pts. Marrow blast % was 〈 =2%, 3–5%, 5–10%, 〉 10 % in 2%, 3%, 18% and 77% pts. Overall IPSS-R could be calculated in 259 patients and was low (1 pt), Intermediate (28 pts, 11%), high (87 pt, 34%) and very high (143 pt, 55% pts). The only pt in the low group was excluded from further analysis. Using the “classical” IPSS, high and Int-2 patients treated with AZA had significantly different Response (37% vs 49%, p=0.05) and OS (median 9.4 vs 16 mo, respectively, p=0.004). Using the IPSS-R, 46%, 47% and 39% responded (CR, PR, or Hematological improvement- HI) to AZA in the int, poor and very poor groups, respectively (p=0.463). Individual IPSS-R parameters, including IPSS-R cytogenetic classification (p= 0.646), Hb level (p= 0.948), platelet count (p=0.10), ANC (p= 0.465) and marrow blast % stratified according to R-IPSS (p=0.287) had no significant impact on AZA response. According to IPSS-R cytogenetic classification, median OS was 21.8 mo, 12.3 mo, 15.1 mo and 7.1 mo in the good, int, poor and very poor risk groups respectively (overall p 〈 10−4). Finally, According to IPSS-R, median OS was 30.7 mo, 17.6 mo, and 10 mo in the Intermediate, High and Very High risk groups, respectively (p 〈 10−4, figure 1). I. The 55% patients with very high risk according to IPSS-R could be further subdivided by our AZA scoring system (Itzykson et al, Blood, 2011) in 3%, 67% and 30% low, int or high risk with a significant different OS across those groups (median not reached (NR), 12.7 and 5.9 mo, p 〈 10−4). Similarly, The 34% patients with high risk according to IPSS-R could be further subdivided by the same AZA scoring system in 6%, 80% and 14% low, int or high risk with a significant different OS across those groups (median NR, 17.3 and 6.1 mo, p 〈 10−4). Conclusion: Contrary to the provisional IPSS-R presented in 2011, the final IPSS-R (Greenberg, Blood 2012) has strong prognostic value for survival in MDS pts treated with AZA.Its prognosic value can be further improved by specific scoring systems established for AZA treatment, like the one published by our group (Itzykson, Blood, 2011). Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 4
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2906-2906
    Abstract: Abstract 2906 Background: Cardiac complications of transfusional iron overload are well documented in various inherited anemias. In regularly transfused MDS, the deleterious role of iron overload on cardiac disease is more disputed, due in particular to frequent concomitant causes of cardiac failure. Cardiac MRI T2* allows accurate and specific measurement of iron content. Methods: We prospectively evaluated in 4 centers of the GFM by standardized and transferable MRI methods both cardiac T2* according to Anderson (Eur Heart J. 2001Dec;22(23):2171-9) and liver iron content (LIC) according to Gandon (Lancet. 2004 Jan 31;363(9406):357-62), as well as cardiac function by routine echocardiography or MRI in regularly transfused MDS patients. Results: From Dec 2005 to March 2010, 73 patients (pts) were included (14 of them had more than one MRI evaluation over time): 38 M/35F, Median age 68 (24-86); WHO : RA=5, RARS=33, RMCD-RS=3, RMCD=1, RAEB1=9, RAEB2=5, RAEB-T/AML=1, 5q- syndrome=8 and unclassified=8; Karyotype: fav n=50, Int n=9, unfav n=4, failure n=10; IPSS: low n=29, Int-1 n=28, Int-2 n=5 and High n=1, unknown n=10. Median interval from MDS diagnosis and MRI T2* assessment was 49 months (range 0–324). Median serum ferritin at MRI assessment was 1750 ng/ml (range 282–7339) and 54/73 pts were on chelation therapy (CT) (median duration of CT prior to first MRI: 18 months, range 1–125). 37/73 pts had cardiac symptoms and 28 were on cardiac therapy. At first MRI T2* analysis, the median number of RBC units transfused was 68 (range 5–574). Median LIC was 330 micromoles/g/dw (range 40–908). Median Cardiac T2* was 27 ms (range 6–74). 14/73 pts had cardiac iron overload defined by MRI T2* ≤20 ms (19%) and among them 3/73 (4%) had severe cardiac iron overload (T2*≤ 10 ms). LVEF was below normal (55%) in 13/59 cases evaluated. A correlation was found between cardiac T2*and the number of RBC units transfused (Pearson correlation =-0.342, p=0.004) but not with LIC (p= 0.65) and serum ferritin (p=0.21). Cardiac overload was seen in 1/19 (5.5%) pts transfused 〈 50 RBC units, 4/37(12.1%) pts transfused 50–150 units, 9/17 (52.9%) pts transfused 〉 150 units (p= 0.0005). Those 3 pt subgroups also differed in median LIC (μmoles/g/dw) ( 〈 50 units= 250, 50–150 units=340, 〉 150 units=414) (p=0.044 Kruskall-Wallis' test), but not significantly in serum ferritin (p= 0.085). No significant correlation was found between decreased LVEF ( 〈 55%) and cardiac T2* 〈 20 ms (p=0.5), or T2*≤10 ms (p=0.23). In particular, 5/13 pts (38%) with LVEF 〈 55% had T2* 〈 20ms, vs versus 8/46 pts (17%) with LVEF 〉 55% (p= 0.13). However, 1/14, 0/30 and 3/12 pts having received 〈 50, 50–150 and 〉 150 RBC units had severe cardiac failure (ie LVEF≤35%)(p=0.012). 3/4 pts with severe cardiac failure had T2* 〈 20ms,compared to 8/54 pts without severe cardiac failure (p=0.023). 14 pts had another cardiac MRI 6 to 34 months (median 18) after the first. All were on CT and had received a median of 60 and 214 PRBC units at first and last MRI, resp. Median Cardiac T2* was 21.6 ms (range 8.5–35.3) and. 28 ms (range 6.4–41) at last and at first assessment, respectively (p=0.3) Conclusions: Moderate and severe post transfusional cardiac iron overload was seen in 19% and 4% of regularly transfused MDS, respectively. The level of cardiac iron overload was well correlated to the number of RBC transfused. The impact of cardiac overload on LVEF was unclear except in pts with severe cardiac impairment (LVEF 〈 35%), possibly suggesting that iron overload is only one of the factors responsible for cardiac disease in many of those elderly patients. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 5
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 4003-4003
    Abstract: Abstract 4003 Introduction: Azacytidine (AZA) has significantly improved the management and survival of patients (pts) treated for high risk myelodysplastic syndrome (MDS). However, 40 to 50% of patients will not achieve any kind of response and most responders relapse within 2 years (Fenaux Lancet Oncology 2009). Aternative strategies are so required for this population with primary or secondary failure of AZA. Vorinostat is a second generation histone deacetylase inhibitor with significant clinical activity in MDS and leukemia, although the response rate remains low (Garcia-Manero Blood 2008). Synergy of vorinostat with both conventional cytotoxic agents and targeted therapy has been demonstrated in vitro and in vivo (Esteller NEJM 2008). Methods: In this still ongoing study (clinicaltrials.gov NCT00776503), we combined low-dose cytarabine (10-20 mg/m2/day for 14 days sub-cutaneously) and escalating total doses of vorinostat. Two schedules of vorinostat, (400mg/day orally) beginning on day 1 (arm A) or on day 14 (arm B), were tested in 3 groups receiving escalating treatment duration (7days, 10 days and 14 days) following a classical 3+3 phase I schedule. 10 additional pts will be included at the recommended dose level of each cohort (arm A and B). Inclusion criteria were age 〉 18, MDS or AML 〈 30% blast according to WHO, IPSS≥1.5, prior failure of demethylating agent therapy. Toxicity was assessed using CTCAE V3. Results: To date, a total of 34 pts were included and 31 were treated, 21 pts in arm A and 10 pts in arm B. 2 pts died before the beginning of treatment and 1 pt did not fulfill inclusion criteria (no previous AZA). The median age was 71 years (range 46y to 88y), the median number of previous treatments was 2 (1-3) and the median number of cycles of AZA was 10 (range 3–25). All pts had Int-2 (n=15) or High risk MDS (n=16) according to IPSS. A total of 108 cycles of treatment were administered with a median number of 3 cycles/pt and 9 pts had more than 3 cycles. The recommended dose was determined for arm A at 10 days of vorinostat and for arm B at 14 days. The dose limiting toxicities were grade 3 fatigue (n=2), grade 4 bilirubin (n=1) and grade 4 infection (n=2). The most frequent non-limiting toxicities were myelosuppression and GI toxicities. Response was centrally evaluated according to IWG 2006 criteria. The overall response rate was 17% in 29 evaluable pts (2 CRi, 1 HI and 2 marrow CR) with a median duration of response of 3 months (range [2-6+] ). There were 2 responders in arm A (1 in 7 days dose level and 1 in 14 days dose level) and 3 responders in arm B (1 in the 7 days dose level and 2 in the 10 days dose level) including the 2 CRi. 14pts remained stable and 10 progressed during treatment. With a median follow up of 9 months, the median overall survival of the cohort is 7.3 months. Conclusions: The phase I results presented here show that 400 mg/day vorinostat can be combined to LDAC and given for 10 days (arm A) to 14 days (armB) with acceptable side effects. It also suggests that the sequential administration might be associated with an increased therapeutic index since longer vorinostat therapy duration could be tolerated with higher response rate (3/10 vs 2/21). Interestingly, responses were observed in pts with poor risk cytogenetics who generally fail LDAC alone (t(3;3), complexe Karyotype). Accrual of additional pts at the recommended dose in each arm is ongoing. Data will be updated accordingly. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 14 ( 2021-05-10), p. 1575-1583
    Abstract: TP53-mutated ( TP53m) myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) have very poor outcome irrespective of the treatment received, including 40% responses (20% complete remission [CR]) with azacitidine (AZA) alone, short response duration, and a median overall survival (OS) of approximately 6 months. Eprenetapopt (APR-246), a novel first-in-class drug, leads to p53 protein reconformation and reactivates its proapoptotic and cell-cycle arrest functions. PATIENTS AND METHODS This phase II study assessed the safety and efficacy of eprenetapopt in combination with AZA in untreated high or very high International Prognostic Scoring System-R TP53m MDS and AML patients. RESULTS Fifty-two TP53m patients (34 MDS, 18 AML [including seven with more than 30% blasts] ) were enrolled. In MDS, we observed an overall response rate (ORR) of 62%, including 47% CR, with a median duration of response at 10.4 months. In AML, the ORR was 33% including 17% CR (27% and 0% CR in AML with less than and more than 30% marrow blasts, respectively). Seventy-three percent of responders achieved TP53 next-generation sequencing negativity (ie, variant allele frequency 〈 5%). The main treatment-related adverse events were febrile neutropenia (36%) and neurologic adverse events (40%), the latter correlating with a lower glomerular filtration rate at treatment onset ( P 〈 .01) and higher age ( P = .05), and resolving with temporary drug interruption without recurrence after adequate eprenetapopt dose reduction. With a median follow-up of 9.7 months, median OS was 12.1 months in MDS, and 13.9 and 3.0 months in AML with less than and more than 30% marrow blasts, respectively. CONCLUSION In this very high-risk population of TP53m MDS and AML patients, eprenetapopt combined with AZA was safe and showed potentially higher ORR and CR rate, and longer OS than reported with AZA alone.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 7
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 3811-3811
    Abstract: Abstract 3811 Poster Board III-747 Background The European LeukemiaNet has initiated a prospective, noninterventional registration study on newly diagnosed MDS patients with IPSS low and intermediate-1 risk in eleven participating European countries. The main objectives are to describe demographics and to collect data on clinical characteristics, disease management and relevant outcomes. Patients and Methods The registry started accruing patients in April 2008. Until now 478 patients have been registered through a web-based reporting system. This report describes the demographic data of the first 400 registered patients with a median follow up of 177 days. Results The median age of the patients was 74 years. RAEB-1 was the WHO-diagnosis in 13% of the patients while the remaining patients had 〈 5% marrow blasts (RA: 81; RARS: 84; RCMD: 114; RCMD-RS: 26, MDS-U: 16; del(5q): 27). The majority of patients were males 250/400 except within WHO del(5q) which showed a female preponderance 21/27. Cytogenetic data were available in 93% of the patients and 77% had good risk cytogenetic characteristics. IPPS score was 0 in 50% of the patients, 0.5 in 28% patients and 1 point in 15% of the patients. The Karnofsky performance score was reported in 85% of the patients. The Karnofsky index was related to age (p 〈 0.001) and was 〈 80 in 20% of the patients. The EQ 5D status was reported in 82% of the patients. The median EQ 5D score was 70 (4 to 100) and ranged from 50 (40 to 80) in Austria to 87 (50 to 100) in Greece. The mean Sorror Score of Co-morbidity was 2.4 (2.0) and ranged from 1.4 (s.d.1.6) in Greece to 3.0 (s.d 1.8) in France. Cardiac disease was reported in 28% of the patients, pulmonary disease in 13%, diabetes mellitus in 16%, and thyroid disease in 12% of the patients. The Body mass Index was available in 73% of the patients. Overweight (BMI 〉 25) was present in 60% of the reported patients. The median Erythropoietin level (N = 219) was 42 iU/l (3.5 to 2100). The iron status at diagnosis was available in 241 patients. The median serum iron level (N = 240) was 10 mmol/l (range: 3 to 57) with a median transferrin saturation level 39% (N = 107), ranging from 17% in MDS-U to 53% in RARS. The median ferritin level was 341 mg/l (n=289) ranging from 121 mg/l in del(5q) to 577 mg/l in RARS. 37% of the patients received MDS specific treatment, principally erythropoietin (31%) and G-CSF (4%). 27% of the patients received transfusions at registration, ranging from 17% in Greece to 56% in the Netherlands. As expected only 12 patients (3%) received iron chelation therapy in this early phase after diagnosis. The mean ferritin level of these patients was 1638 mg/l. Thirteen patients progressed to high-risk MDS or AML after a median time of 154 days. Sixteen patients have died (9 patients due to non-MDS related causes) after a median of 175 days after diagnosis. In conclusion this European registry shows that is possible to collect detailed demographic data in eleven different countries. The preliminary data show demographic differences. This registry will show the impact of various demographic and clinical variables including socio-economic co-morbidity and health utility variables on the outcome of patients with low-risk MDS. Disclosures: Fenaux: Celgene: Honoraria, Research Funding; Ortho Biotech: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Cephalon: Honoraria, Research Funding; Epicept: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Merck: Honoraria, Research Funding. Hellstrom-Lindberg:Celgene Corp.: Research Funding. Stauder:Celgene: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 8
    In: Blood, American Society of Hematology, Vol. 120, No. 25 ( 2012-12-13), p. 5084-5085
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
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  • 9
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 972-972
    Abstract: Abstract 972 Background: The IPSS published in 1997, based on cytogenetics, marrow blast % and the number of cytopenias, has played a major role in prognosis assessment in MDS. A recently presented (Greenberg, International MDS Workshop, Edinburgh 2011) IPSS provisional update (IPSS-R), using the same parameters but 5 rather than 3 cytogenetic subgroups (Schanz et al, EHA 2010), a new cut off for ANC (0.8 G/L) and different weighing of parameters, appears to refine IPSS prognostic value but, like the original IPSS, was established in pts who had received no disease modifying drugs. We assessed the prognostic value of IPSS-R in 265 higher risk MDS treated with AZA, a drug with a survival impact in those pts (Lancet Oncol, 2009). Methods: Between Sept 2004 and Jan 2009, before drug approval in EU, we enrolled 282 IPSS high and int 2 (higher) risk MDS in a compassionate patient named program of AZA and established in this cohort a prognostic scoring system (“AZA predictive score” based on Performance status (PS), cytogenetics, presence of circulating blasts, and RBC transfusion dependency) (Itzykson, Blood, 2011). We analyzed in this cohort the prognostic impact of IPSS-R in higher risk MDS treated with AZA. Results: Median age was 71 years. WHO diagnosis: 4% RA, RA RARS or RCMD, 20% RAEB-1, 54%RAEB-2, 22% RAEB-t (AML 20–30% blasts). Cytogenetics could be reclassified using new IPSS-R cytogenetic groups in 265 pts, in: 1% very good, 37% good, 18% int, 12% poor and 32% very poor. 66% pts had Hb 〈 10g/dl, 74% had Platelets 〈 100 G/L and 45% had ANC 〈 0.8 G/l. Marrow blast % was 〈 5%, 5–10%, 11–20%, 21–30% in 6%, 22%, 54% and 18% pts. Overall R-IPSS in the 265 patients was very good (no pt), Good (2 pts, 〈 1%), intermediate (int 9.5%) poor (23%) and very poor (67% pts). The 2 pts of the Good group were excluded from further analysis. 56%, 55% and 38% had a response (CR, PR, or Hematological improvement- HI) to AZA in the int, poor and very poor R-IPSS groups, respectively (p=0.029). However, individual IPSS-R parameters, including IPSS-R cytogenetic classification (p=0.39), Hb level (p=0.42), platelet count (p=0.10), ANC (p=0.25) and marrow blast % (p= 0.129) stratified according to R-IPSS had no significant impact on AZA response. According to IPSS-R cytogenetic classification, median OS was 22.6 mo, 12.3 mo, 15.1 mo and 7.1 mo in the good, int, poor and very poor risk groups respectively (overall p 〈 10−4, Int vs poor: p=0.85, figure 1). According to IPSS-R, median OS was 30.7 mo, 23.1 mo and 10 mo in the int, poor and very poor R-IPSS groups respectively (Int vs poor: p=0.7; poor vs very poor: p 〈 10−3), figure 2). Thus, there was no OS difference between patients with Int and Poor R-IPSS, who represented 32% of the patients. Among those 85 patients, however, 5%, 70% and 25% respectively could be assigned to the high, intermediate and low risk groups of our AZA predictive score (Itzykson, Blood 2011) with significant differences in OS between the 3 groups (median 6.1 mo, 21 mo and not reached, respectively, p= 0.0001). Our AZA predictive score was also valid in the Very Poor R-IPSS group, with a median survival of 5.9 mo, 12.3 mo and not reached (p 〈 10−4) in the high, int, low risk respectively. Using the “classical” IPSS, high and Int-2 patients treated with AZA had significantly different Response (37% vs 49%, p=0.05) and OS (median 9.4 vs 16 mo, respectively, p=0.004). Conclusion: In high and int 2 risk MDS (with current IPSS) treated with AZA, the R-IPSS could predict response to AZA but found no different OS between intermediate and Poor risk patients, who represented one third of the population. Thus, refined prognostic systems established in untreated patients may have to be complemented by more specific scores when using disease-modifying drugs, like our AZA predictive score in AZA treated patients. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 10
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 2614-2614
    Abstract: Abstract 2614 Background: The efficacy of conventional treatment in older patients with acute myeloid leukemia remains unsatisfactory, with low remission rates and poor overall survival. Disappointing results of intensive chemotherapy in patient over 60y are explained by decreased bone marrow reserve and high chemoresistance rate. Novel treatment approaches for this age group are needed. Among these options, 5-azacytidine (AZA) have shown promising results, improving survival in high-risk myelodysplastic syndrome including patient with 20–29% marrow blast now considered WHO AML. Methods: AML patients (marrow blast≥20%) considered not candidates for ICT and treated frontline with only AZA in Toulouse University Hospital were retrospectively analyzed in this study. AZA 75 mg/m2/day was administered subcutaneously for 7 days every 4 weeks, which was defined as 1 cycle. Results: Ninety eight patients were registered between June 2007 and Dec 2010. In this period of time, a total of 470 AML patients older than 60 years were referred in our center. 234 received ICT, 98 AZA, and 138 LD-ARAC or BSC. Sex ratio M/F was 56/42 and median age was 76 (range 50–89). Eighty eight patients were 〉 65y and 51 were 〉 75y. Forty eight patients (48.9%) had de novo AML, 27 patients (27.5%) had prior history of WHO MDS, 5 patients (5.1%) had prior history of myeloproliferative disorder and 18 patients (18.3%) had therapy related AML. Median white blood cell (WBC) count was 2.2G/L (range 0.76–62) and median bone marrow (BM) blast was 35% (range 20–85). Karyotype (Medical Research Council classification) was intermediate in 48 patients (48.9%) including 36 normal and 6 trisomy 8, adverse in 44 patients (44.8%) including 24 -5/del5q, 28 -7/del7q, 35 complex karyotype and 21 monosomal karyotype, and failed in 6 patients (6.1%). Median follow up in survivors was 12.6 months. Patients received a median of 6 cycles of AZA (range 1–27). All patients received at least 1 cycle of AZA and were considered evaluable for response. Fifty patients (51%) presented a response to AZA. Overall response rate according to AML IWP criteria was documented in 24 patients (24.5%), including 13 CR, 5CRi (18CR/CRi 18.4%), and 6PR (6.1%). The median duration of remission for patients achieving CR or CRi was 9.5months. Among the 74 patients considered as failure according to AML-IWP criteria, 26 additional patients (26.5%) obtained hematological improvement HI (7 pts on 1 lineage, 13 pts on 2 lineages and 6 pts on the 3 lineages). Overall, 60 patients required hospitalization during treatment for neutropenic fever. The death rate during the first two months after AZA initiation was 18.3%, due to AML progression in 83% and to infection in 17% of cases. The unique prognosis factor that impacts the response rate in univariate and multivariate analysis was the cytogenetic risk group. We identified 18 CR/CRi/PR (37.5%) in the intermediate group and 6 CR/CRi/PR (13.6%) in the adverse group (p=0.02). Age, WBC count, BM blast, or secondary status of the AML were not statistically related to the response rate. However, it should be noted that only 14 patients had WBC 〉 10G/L at diagnosis. In the entire cohort 1y OS was 50% and 2yOS was 28%. In univariate and multivariate analysis, intermediate karyotype was statistically linked to longer survival. Achievement of CR/CRi or PR translated in increased survival, and importantly in patient with no AML-IWP response, achievement of HI, even on 1 lineage only, translated in increased survival. Moreover when comparing patient treated with 1 or 2 courses, with patient receiving 3 or more courses, we noted a significant improve in survival while number of courses increased. Conclusion: AZA appears to be a valuable option for WHO AML patients considered unfit for chemotherapy and with a low WBC count. In this cohort of very old patients, response rates and more importantly survival rates with AZA are promising. Although, pretreatment prognosis factor such as high risk cytogenetic remains adverse factor, predictive factors of response are needed to guide therapeutic decision. Disclosures: Off Label Use: Azacytidine is approved by FDA and EMEA in the treatment of high risk MDS and AML up to 30% of bone marrow blast. In our study, Azacytidine use was supported by the published results of the French compasionate Azacytidine program in WHO AML patients with more than 30% blast. Recher:Celgene: Membership on an entity's Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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    detail.hit.zdb_id: 80069-7
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