Acute Myeloid Leukemia In Older Patients Research Articles

Novel Approaches to the Treatment of Acute Myeloid Leukemia

Approximately 12 000 adults are diagnosed with acute myeloid leukemia (AML) in the United States annually, the majority of whom die from their disease. The mainstay of initial treatment, cytosine arabinoside (ara-C) combined with an anthracycline, was developed nearly 40 years ago and remains the worldwide standard of care. Advances in genomics technologies have identified AML as a genetically heterogeneous disease, and many patients can now be categorized into clinicopathologic subgroups on the basis of their underlying molecular genetic defects. It is hoped that enhanced specificity of diagnostic classification will result in more effective application of targeted agents and the ability to create individualized treatment strategies. This review describes the current treatment standards for induction, consolidation, and stem cell transplantation; special considerations in the management of older AML patients; novel agents; emerging data on the detection and management of minimal residual disease (MRD); and strategies to improve the design and implementation of AML clinical trials.

A Population-Based Study In Acute Myeloid Leukemia (AML) Suggests Improved Overall Survival (OS) up to Age 80 with Intravenous Therapy: 2000–2007 Data From the Surveillance, Epidemiology, and End Results (SEER)-Medicare Registry In the United States (US),

Abstract 3589 Background:AML is the most common leukemia among US adults with median age of 69. Earlier 1990s studies reported a median OS was 2.4 months among patients older than age 65. Considering the trends in older AML treatment might have changed during the last decade, we investigated clinical practice for older AML patients. Methods:Patients age ≥ 66 in the National Cancer Institute’s (NCI) SEER cancer registry with a first, primary cancer of AML diagnosed between January 2000 and December 2007 were matched to their Medicare Part A and Part B claims for long-term follow-up. Diagnostic evaluation and treatment patterns with disease outcomes were assessed. There were 4633 AML patients identified, and 1791(38.6%) received intravenous leukemia therapy within 3 months of diagnosis (treatment group). Treated patients then were sub-grouped as receiving chemotherapy (chemo) (94.9%) and hypomethylating agents (hypo) (5.1%). Results:The median age of the study population was 78. Treatment group had similar demographics compared to the no treatment group except they were younger (median age, 74 vs. 80, p<0.01) and more were male (56.9 % vs. 48.8%, p<0.01). Median Charlson comorbidity score (CCS) were similar (median, 0) but less patients in treatment group had CCS ≥ 2 (13.0% vs. 20.1%, p<0.01). Patients in treatment group received more extensive diagnostic work-up including: flow cytometry (72.3% vs. 50.8%, p<0.01), cytogenetics (48% vs. 27.4%, p<0.01) and human leukocyte antigen (HLA) typing (6.8% vs. 0.6%, p<0.01).Median OS was 3 months, but superior in the treatment group (7 mo. vs. 2 mo, p<0.01). This benefit was demonstrable in all age groups with greatest improvements in age 66–69 (10 mo. vs. 4 mo, p<0.01) and 70–74 (8 mo. vs. 3 mo, p<0.01) (Figure 1). Older age and CCS ≥2 were also associated with decreased OS (HR=1.04 (for each year), p<0.01 and HR=1.3, p<0.01 respectively). Within the treatment group, 2-month mortality after treatment was 31.2 % with the lowest level in age groups 66–69 and 70–74 (19.8 % and 25.2 %). Logistic regression analyses revealed that older age and CCS ≥2 were significantly associated with higher 2-month mortality (HR=1.08 (for each year), p<0.01 and HR=1.3, p<0.01 respectively). [Display omitted] Among treated patients, a subgroup analysis of 91 patients receiving hypo showed that they were older than chemo group (median age 78 vs. 74, p<0.01), but had similar CSS scores. Although OS with hypo was increased compared to chemo group (9 mo. vs. 6 mo.) in multivariate analysis this difference was not significant (HR=1.25, p=0.07).Hematopoietic stem cell transplantation (HCT) was performed only in 57 patients (1.2%) after AML diagnosis. Median time to HCT after AML diagnosis was 6 months. These patients were younger (median age 66 vs. 73 in other treated patients) and none had CSS scores >2 (0% vs. 6.1%). Their median OS from diagnosis was 25 months. Conclusion:Intravenous therapy improves OS in older AML patients and most patients up to 80 years of age should be considered for treatment based on their comorbidity status. New therapies including hypomethylating agents and allogeneic HCT are promising and must be compared with other chemotherapy in the appropriately selected population. Disclosures:Weisdorf:Genzyme: Consultancy, Research Funding.

A Phase 1 Study of Sequential Idarubicin + Cytarabine, Followed by Lenalidomide, in Patients with Previously Untreated Acute Myeloid Leukemia (AML)

Abstract 2600 Background:Lenalidomide (Len) is an immunodulatory agent with proven efficacy in lower-risk myelodysplastic syndromes (MDS) and with strong signals of single-agent activity in higher-risk MDS and AML patients (pts). Our preclinical data showed that Len antagonized cytarabine cytotoxicity with simultaneous exposure, while augmenting the effects of anthracyclines and cytarabine with sequential drug exposure. We initiated a phase 1 combination study in patients with AML investigating sequential standard induction chemotherapy followed by Len. Objectives:1) to determine the safety and maximum tolerated dose (MTD) of Len following idarubicin/cytarabine induction. 2) to assess preliminary signs of efficacy of this regimen in adults with previously untreated AML. Methods:This was a multicenter, open-label, dose escalation phase 1 study with a 3+3 dosing design of idarubicin (12 mg/m2, day 1–3), cytarabine (100 mg/m2, CI day 1–7) + Len (starting dose 5 mg, day 8–21). Len dose was escalated in 5 mg increments up to a maximum of 25 mg/day. Eligibility included pts with AML age ≥60 years or age <60 with associated del 5/5q; or MDS/RAEB-2 with prior hypomethylating agent failure. Other inclusion criteria included: ECOG PS 0–2 and adequate end-organ function (including normal LVEF of ≥ 50%). Pts who achieved CR/CRi after 1 or 2 cycles of induction were eligible to receive post-remission idarubicin/cytarabine/Len (at the same dose level) for up to 2 cycles, followed by Len maintenance 10 mg/day for up to 12 months. The MTD cohort was expanded to 10 patients. Results:Of 23 enrolled and treated pts, 21 have completed at least 1 treatment cycle. Median age was 68 years (range 44–79); males: 18 (78%). Eleven pts had del 5/5q associated karyotype (10 of whom had complex karyotype), and 15 had secondary AML (including 8 who received prior hypomethylating agents). Len dose escalation reached 25mg/day, with MTD determined to be 20 mg/day. Dose-limiting toxicities occurred in 2 of 3 patients treated at Len 25 mg/day (grade 3 rash; grade 4 neutropenia and thrombocytopenia persisting beyond day 56) and in 1 of 8 patients treated at Len 20 mg/day (grade 4 cardiac ischemia). Only 1 of 21 (5%) patients died within 30 days of treatment initiation. The most common therapy-related non-hematologic toxicities (occurring in ≥ 20% of patients, the vast majority of which were grade 1–2) included: diarrhea (76%), infection/febrile neutropenia (71%), rash (62%), nausea (43%), pain (43%), hemorrhage (33%), fatigue (29%), and non-neutropenic fever (24%). Of the 20 patients evaluable for response, 7 achieved CR and 1 CRi, for an overall response rate (ORR) of 40%. Of 11 evaluable patients treated at the MTD (Len 20 mg/day) and higher, the ORR was 55%. CR occurred in 3 out of 10 (30%) patients with associated del 5/5q. Conclusion:Sequential idarubicin/cytarabine + Len was generally well-tolerated in a primarily older population of patients with previously untreated AML, with MTD of 20 mg/day for Len. Clinical activity in this poor-risk population appears promising at the MTD and higher. Further exploration of this regimen in older AML patients is warranted, with plans for a phase 2 expansion underway. Updated toxicity, response, and survival data will be presented. Disclosures:Lancet:Celgene: Research Funding. Off Label Use: Lenalidomide is approved for use in MDS. Its investigational role in AML will be discussed. Komrokji:Celgene: Honoraria, Research Funding, Speakers Bureau. Sekeres:Celgene: Advisory Board. List:Celgene: Consultancy.

Older Patients with Acute Myeloid Leukemia (AML) in First Relapse: Impact of Genetics and of Salvage Therapy. A Study of the Acute Leukemia French Association (ALFA)

Abstract 253 Aim.AML in older patients constitutes the majority of AML cases, still associated with a high relapse rate after intensive chemotherapy (ICT). Relapsing patients are frequently targeted for new drug development, but few data are available on their outcome and optimal management. With the aim to provide historical data for future drug evaluation, we retrospectively analyzed a cohort of 393 patients aged ≥50 years in first relapse after prospective inclusion in ALFA 9801 (NCT00931138) and 9803 (NCT00363025) ICT trials. Patients.Median age was 64 years (50–82). Median duration of first complete remission (CR1) was 9 months (1–69). Twelve patients had prior allogeneic stem cell transplantation. At diagnosis, cytogenetics was as follows: 16 favorable (4%), 240 intermediate (61%), 76 adverse (19%), and 61 failed or not done (16%), 173 patients having a normal karyotype (NK). Twenty-nine of 174 patients tested at diagnosis had FLT3-ITD (17%), while the incidence of NPM1, CEBPA, IDH1, IDH2 or WT1 mutation was 24%, 4%, 9%, 10% and 2%, respectively. Among 86 NK-AML patients tested, 24 had a favorable genotype (NPM1 or CEBPA mutation without FLT3-ITD). At relapse, median WBC was 3.4 × 109/L and ECOG-PS >1 in 28% of patients. Relapse management was best supportive care (BSC, 32%), low-dose cytarabine (LDAC, 12%), ICT (38%), ICT combined with gemtuzumab ozogamicin (GO, 5%), or GO alone (10%). As expected, patients who received LDAC or BSC were significantly older and tended to have more frequent unfavorable karyotype. Conversely, patient and AML characteristics were comparable in the ICT, ICT+GO, and GO subsets. Results.Complete remission (CR) rate was 31% and median post-relapse survival was 6.8 months (0%, 17%, 53%, 80%, 42.5% and 3.2, 5.6, 9, 19.8, 8.9 months in BSC, LDAC, ICT, ICT+GO, and GO subsets, respectively). CR2 rate and post-relapse survival were comparable in both GO and ICT subsets, while CR2 rate was higher (P=0.02) and survival longer (P=0.04) in the ICT+GO versus the ICT subset. Median post-relapse survival was 17.3 months in patients who achieved CR2 versus 4.2 months in those who did not (p<0.001). In univariate analysis, age, CR1 duration, WBC, ECOG-PS, and favorable karyotype influenced both CR2 rate and post-relapse survival. Median post-relapse survival reached 16.2 months in patients with favorable karyotype versus 6.2 months in other patients (P<0.001). The presence of FLT3-ITD at diagnosis was associated with shorter post-relapse survival (3 versus 7 months, P=0.03). Interestingly, outcome was similar in NK patients with or without a favorable genotype, as well as in patients with an intermediate or even an adverse karyotype. Besides favorable karyotype, multivariate analysis allowed to identify CR1 duration <12 months (HR, 1.8; P<0.001), ECOG-PS ≥2 (HR, 2.0; P>0.001), age (P=0.001) and WBC (P=0.03), but not FLT3-ITD, as independent factors for shorter survival. To evaluate the role of the different management options, which were dependent of patient and disease characteristics as well as physician’s choice, we matched patients treated intensively (ICT/ICT+GO/GO) to those not treated intensively (LDAC/BSC) using a propensity score. This methodology allows comparing both approaches by reducing the multidimensional covariates associated with the intensive option to a single one-dimensional score used for patient matching. In 76 patient pairs, intensive salvage (HR, 0.49, P<0.001), good ECOG-PS (HR, 0.44, P<0.001), and CR1 duration ≥12 months (HR, 0.55, P=0.001) were associated with longer post-relapse survival. The benefit associated with intensive treatment was more marked in patients with CR1 duration ≥12 months (1-year post-relapse survival, 58% versus 24%; P=0.001) than in those with CR1 duration <12 months (1-year post-relapse survival, 25% versus 13%; P=0.09). Conclusion.If, as expected, favorable karyotype and longer CR1 duration predicted better post-relapse outcome in older AML patients, other karyotypes or genotypes did not. Patients with CR1 duration ≥12 months did benefit from intensive salvage. Intensive treatment should thus remain the current control arm in trials evaluating new alternatives in late relapsing patients, while LDAC/BSC may still be considered as an adequate control arm in patients relapsing within the first year of CR1. Results observed with GO-containing salvage also suggest that GO studies should be actively pursued in this setting. Disclosures:No relevant conflicts of interest to declare.

Fludarabine, Cytarabine, and Attenuated-Dose Idarubicin (m-FLAI) Induction for Elderly Patients with Acute Myeloid Leukemia: Results of a Multicenter Phase II Study,

Abstract 3626 Introduction:Although there have been remarkable improvements in treatment of acute myeloid leukemia (AML), the prognosis of AML in elderly patients remains poor, and the best induction chemotherapy for these patients remains yet unknown. To devise an effective induction regimen for elderly patients with AML, we conducted a phase II trial to evaluate the efficacy and safety of the modified fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) regimen in these patients. Patients and Methods:Elderly (60 years or older) AML patients who did not receive previous chemotherapy were enrolled. Patients received two consecutive cycles of m-FLAI chemotherapy as an induction. The m-FLAI regimen was comprised of fludarabine (25mg/m2, days 1–4), cytarabine (1000mg/m2, days 1–4), and attenuated-dose idarubicin (5mg/m2, days 1–3). The primary end point was complete remission (CR) rate. Results:A total of 108 patients (median age 68.4 years, M:F=64:44) were enrolled. CR was achieved in 62.9% of patients, and treatment-related mortality rate (TRM) was 25.8%. Median overall survival (OS) was 9.3 months, and median event-free survival (EFS) was 6.6 months. The mortality at 30 and 60 days was 18% and 24%, respectively. Performance status and comorbidity did not have prognostic value in these patients. Bone marrow expression of CD117 was related to long EFS and OS. Conclusion:In conclusion, m-FLAI is a safe and effective induction regimen for previously untreated AML in elderly patients. Bone marrow CD117 expression is an independent good prognostic factor in these patients. (ClinicalTrials.gov number, NCT01247493) [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

A phase 2 study of lenalidomide monotherapy in patients with deletion 5q acute myeloid leukemia: Southwest Oncology Group Study S0605

AbstractOlder acute myeloid leukemia (AML) patients with a chromosome 5q deletion have poor outcomes with conventional chemotherapy. This phase 2 study explored the safety and efficacy of single-agent lenalidomide in previously untreated older AML patients with del(5q) who declined standard chemotherapy. Patients were treated with lenalidomide 50 mg daily for 28 days as induction therapy and 10 mg daily for 21 days of a 28-day cycle as maintenance until disease progression or unacceptable toxicity. Among 37 evaluable patients, the median age was 74 years (range, 60-94), 21 (57%) were female, 19 (51%) had prior myelodysplastic syndrome, and 30 (81%) had pretreatment cytogenetic studies evaluated centrally. Six had isolated del(5q), 1 had del(5q) and +8, 23 had complex cytogenetics, and 7 others had del(5q) identified locally. Fourteen patients (38%) completed induction therapy: 7 patients died during induction therapy, 8 had disease progression, 7 had nonfatal adverse events, and 1 entered hospice. Eight patients started maintenance therapy. Five patients (14%) achieved a partial or complete response, 2 with isolated del(5q) and 3 with complex cytogenetics. Relapse-free survival was 5 months (range, 0-19). Median overall survival was 2 months for the entire population. In conclusion, lenalidomide as a single agent has modest activity in older del(5q) AML patients. Southwest Oncology Group Study S0605 is registered at www.clinicaltrials.gov as NCT00352365.

Quality of Life Issues in Elderly Acute Myeloid Leukemia Patients

The median age of acute myeloid leukemia (AML) is 70 years. Treatment approaches include standard chemotherapy, palliative chemotherapy and investigational agents, depending upon disease biology and patient factors. In this article, we highlight the issues involved in the treatment of AML in older patients, focusing on the quality of life changes associated with each treatment modality at different stages of their disease course. We further discuss recent insights into the biological basis of quality of life changes, and examine potential ways to improve these through pharmacological and nonpharmacological means. Finally, we explore avenues for future research into the quality of life of the older AML patient.

Novel Agents for the Treatment of Acute Myeloid Leukemia in the Older Patient

The incidence of acute myeloid leukemia (AML) increases with age, with a median age at diagnosis of 67 years. Older patients have inferior responses to chemotherapy, including not only lower complete remission rates but also short disease-free survival in those who do achieve complete remission. For older patients with a high likelihood of response to chemotherapy, recent data support dose intensification and strong consideration of allogeneic hematopoietic stem cell transplantation. For those unlikely to benefit from chemotherapy because of disease- and/or patient-related factors, novel agents and approaches are being pursued. Agents currently available or under study include the nucleoside analogs clofarabine and sapacitabine, the demethylating agents decitabine and azacitidine, the immunomodulatory agent lenalidomide, and the farnesyl transferase inhibitor tipifarnib. These agents may be administered in the outpatient setting, thus AML in older patients is increasingly becoming an outpatient diagnosis. Additionally, novel agents may prolong survival without inducing complete remissions, and therefore the goals and end points of therapy are also shifting. AML in older patients is a very active current area of investigation.

A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia

AbstractOlder patients with acute myeloid leukemia (AML) have limited treatment options and a poor prognosis, thereby warranting novel therapeutic strategies. We evaluated the efficacy of lenalidomide as front-line therapy for older AML patients. In this phase 2 study, patients 60 years of age or older with untreated AML received high-dose (HD) lenalidomide at 50 mg daily for up to 2 28-day cycles. If patients achieved a complete remission (CR)/CR with incomplete blood count recovery (CRi) or did not progress after 2 cycles of HD lenalidomide, they received low-dose lenalidomide (10 mg daily) until disease progression, an unacceptable adverse event, or completion of 12 cycles. Thirty-three AML patients (median age, 71 years) were enrolled with intermediate (55%), unfavorable (39%), or unknown (6%) cytogenetic risk. Overall CR/CRi rate was 30%, and 53% in patients completing HD lenalidomide. The CR/CRi rate was significantly higher in patients presenting with a low (< 1000/μL) circulating blast count (50%, P = .01). The median time to CR/CRi was 30 days, and duration of CR/CRi was 10 months (range, 1- ≥ 17 months). The most common grades ≥ 3 toxicities were thrombocytopenia, anemia, infection, and neutropenia. HD lenalidomide has evidence of clinical activity as initial therapy for older AML patients, and further study of lenalidomide in AML and MDS is warranted. This study is registered at www.clinicaltrials.gov as #NCT00546897.

Effect of Complete Remission Achievement on Survival In Acute Myeloid Leukemia of the Elderly.

AbstractAbstract 1048The achievement of complete remission (CR) is considered an essential prerequisite for cure in acute myeloid leukemia (AML). Notwithstanding, in older AML patients recent data suggest that, at least for patients receiving new compounds such as hypomethilating agents Azacytidine and Decitabine, the benefit on survival can be independent from CR achievement, namely in patients with low bone marrow blast count (< 30%) at diagnosis. In this study we evaluated the impact of CR achievement on overall survival from a series of 140 patients aged over 60 years; all patients received a therapeutic program including continuous infusion of fludarabine (F) and cytarabine (ARA-C) as induction and consolidation, followed whenever possible by autologous stem cell transplantation (Ferrara et al, Haematologica, 2005). Briefly, F was administered at a loading dose of 10 mg/m2 over 15 min at day 0 followed 6 hours and half later by continuous infusion (c.i.) of 20 mg/m2/24 hours for 72 hours (days 0–2); ARA-C was given at a loading dose of 390 mg/m2 three hours and half after F and then as c.i. over 96 hours at 1440 mg/m2/24 hours (days 0–3). G-CSF was added at day +15 at a dose of 5 μg/kg. A second identical course was planned for patients obtaining partial response, defined as less than 5% blasts in peripheral blood and less than 30% of blasts in the bone marrow. Patients achieving CR, established as less than 5% blasts in the bone marrow, normal blood count and differential and absence of extramedullary leukemia, were programmed to receive an additional identical course as consolidation, reduced of one day (i.e. two days c.i. of F and three days c.i, of ARA-C). The effect of CR was separately analyzed according to karyotype, bone marrow blast count and, in patients with normal karyotype, NPM1 and FLT3 positivity. Of note, patients dead in induction were excluded from survival benefit evaluation. The median age was 69 years (range 61–82). Cytogenetic analysis was successfully in 134/140 patients (96%). Among these 89 (66%) were found as having normal karyotype (NK) and 45 (34%) with different chromosomal abnormalities, mostly complex or involving chromosomes 5 and/or 7, classified as unfavorable (UK). Overall 94 patients (67%) achieved CR; the CR rate was 77 % in NK and 47% in unfavorable karyotype (p:<0.001). Of note, rates of either death in induction (22% vs 14%) or primary refractory disease (33 % vs 8%) were significantly higher in patients with adverse cytogenetics. The median survival for the whole patient population was 10 months; survival was significantly influenced by cytogenetics at diagnosis (12 months for NK vs 7 months for UK), p:<0.001). The median duration of CR was 11 months (16 months for patients with NK as opposed to 7 months for those with UK). The overall impact of CR achievement on survival was remarkable and remained statistically significant after exclusion of patients dead in induction (18 months vs. 6 months, p:< 0.001). The advantage of achieving CR was found in patients with NK, independently from molecular assessment at diagnosis, i.e. NPM1+/FLT3-, NPM1-FLT3-, NPM-FLT3+, NPM+/FLT3+). Of interest, no difference was found as bone marrow blast count at diagnosis, i.e. more or less than 30 %, was concerned in the rate of CR achievement, CR duration and impact of CR on survival either in univariate or multivariate analysis. By separately analyzing patients with UK, the advantage of CR achievement was found only when patients dead in induction were excluded and was limited to 4 months (11 months for remitters vs. 7 months for refractory patients, p:0.04). We conclude that older AML patients with unfavorable karyotype have lower CR rates following conventional chemotherapy, because of higher mortality in induction and more frequent refractory disease; in addition, CR is shorter when compared to patients with normal karyotype and has limited impact on survival. Accordingly, even when clinically eligible for aggressive chemotherapy, such patients should be included into therapeutic programs based on experimental programs including agents with alternative mechanisms of action. Disclosures:No relevant conflicts of interest to declare.

Monosomal Karyotype (MK) In Older Patients with Acute Myeloid Leukemia (AML) on Eastern Cooperative Oncology Group (ECOG) Therapeutic Trials: Poor Prognostic Impact of MK, but Not of Monosomy 7

AbstractAbstract 579 Background:In AML, age and cytogenetics remain among the major prognostic factors. Age above 55 years and a complex karyotype (CK; ≥ 3 abnormal clones) or the presence of monosomy 7 (M7) are universally associated with unfavorable prognosis. Recent data from HOVON-SAKK (J Clin Onc 26: 4791) suggest that in patients under the age of 60 years, subgroups with poor risk versus very poor risk can be delineated based on the presence of a MK. MK was defined as either the presence of at least two autosomal monosomies or one monosomy plus at least one structural abnormality. Limited data exists regarding the impact of MK in AML patients over the age of 55 years. Methods:Data from 935 AML patients above age 55 enrolled on three prospective ECOG therapeutic clinical trials (E1490, E3993, E3999) between 1990 and 2005 were retrospectively reviewed to identify those with MK with single and/or multiple monosomies, MK in the presence or absence of a CK, CK with/without MK, MK with/without M7, and normal karyotype (CN). CK was defined as ≥ 3 clonal abnormalities for the purposes of this study. Complete remission (CR), disease-free survival (DFS), and overall survival (OS) were assessed. Results:The median age of evaluable patients was 68 years (range 56 – 93) with a male/female ratio of 391/299. Cytogenetic data were evaluable in 690 (74%) subjects. Clonal cytogenetic abnormalities occurred in 399 (58%). Core-binding factor (CBF) abnormalities accounted for 16/399 (4%) whereas CK was detected in 181/399 (45%). MK was present in 172 (25%) evaluable cases, predominantly in the setting of CK (140/172, 81%). Overall CR was 44%. CR was achieved in 49% MK−, 29% MK+, 31% CK+, and 49% of CK−. Data for the combinations of MK and CK are presented in Table 1. Median follow-up for survivors was 5.0 years. OS at 4-years was 9% for all evaluable patients and 4y-DFS was 12% in those achieving CR. Median OS of MK+/CK+ (0.3y) was significantly worse (p<0.001) than MK+/CK−(0.6y), MK−/CK+ (0.8y), and MK−/CK−(0.9y). Median DFS of MK+/CK+ (0.3y) was also significantly poorer (p<0.001) than MK+/CK− (0.9y), MK−/CK+ (0.8y), and MK−/CK− (0.9y). M7 was present in 82 (13%) enrolled patients with 98% (80/82) of M7 occurring within a MK. CR was achieved in 31% of MK+/M7+ and 27% of MK+/M7−. Neither median OS nor DFS were significantly impacted by M7 status as noted in Table 2. Conclusions:AML patients above the age of 55 years have an unfavorable prognosis with the majority of patients harboring adverse clonal cytogenetic abnormalities and failing to achieve a CR. Fewer than 10% survive 4-years from diagnosis. Results from the ECOG experience demonstrate the prognostic predictive value of MK in older AML patients. In contrast to the data presented by the HOVAN-SAKK group, the prognostic value of MK in patients over 55 years is limited to those with MK in combination with CK. These results also demonstrate the failure of monosomy 7 to provide prognostic value in the setting of MK.Table 1Outcome data related to Monosomal and Complex KaryotypesMK−/CK−MK−/CK+MK+/CK−MK+/CK+N4754132140CR51%37%28%29%4y-OS12%10%6%0%4y-DFS15%7%0%0%OS, median (years)0.90.80.60.3p<0.001DFS, median (years)0.90.80.90.3p<0.001Table 2Outcome data related to Monosomal Karyotype and Monosomy 7MK+/M7−MK+/M7+N9280CR27%31%4y-OS2%1%4y-DFS4%0%OS, median (years)0.30.5p= 0.062DFS, median(years)0.40.5p= 0.240 Disclosures:No relevant conflicts of interest to declare.

Prognostic Impact of Wilms Tumor 1 Single Nucleotide Polymorphism rs16754 In Older Patients with Acute Myeloid Leukemia

AbstractAbstract 2701The Wilms tumor 1 (WT1) gene, located at chromosome band 11p13, encodes a transcriptional regulator involved in normal hematopoietic development. The role of WT1 in acute myeloid leukemia (AML) has been underlined by the finding of WT1 overexpression in most AML cases and WT1 gene mutations in approximately 10% of AML patients. Recently, the minor allele of the silent Arg301 single nucleotide polymorphism (SNP) (rs16754), which is a 903A>G substitution in WT1 exon 7, was suggested to predict a favorable prognosis in adult patients with cytogenetically normal (CN) acute myeloid leukemia (AML). In contrast, no prognostic impact of this SNP was found in another study performed in pediatric AML. Our aim was to evaluate the frequency, the main associated features and the prognostic significance of WT1 SNP rs16754 in elderly patients with AML. Diagnostic bone marrow or peripheral blood samples were analyzed from 266 patients (age 50 to 70 years) with previously untreated de novo AML included in the French ALFA-9801 trial. WT1 SNP rs16754 and gene mutations of NPM1, CEBPA, FLT3 (internal tandem duplication, ITD), WT1 (exon 7 and 9), IDH1 and IDH2 (exon 4) were screened on genomic DNA by direct sequencing and fragment-length analysis for the detection of small insertion/deletion. The minor allele of WT1 SNP rs16754 was found in 85 (32%) out of 266 cases. Patients heterozygous or homozygous for minor allele (WT1AG or WT1GG) and patients homozygous for the major allele (WT1AA) did not significantly differ in terms of age, gender, white blood cell (WBC) count, FAB subtypes, cytogenetic categories, and gene mutations when those mutations are considered separately. However, among CN-AML, the frequency of the favorable genotype defined by the presence of NPM1 mutation or CEBPA mutation without neither FLT3-ITD nor IDH1 mutation was significantly lower in patients with at least one minor allele than in patients with two major alleles (5% vs 23% of CN-AML, p=0.02). In univariate analysis, complete remission rate was found similar between patients with at least one minor allele and patients with two major alleles (76% vs 75%, p=0.88). Patients with at least one minor allele tended to have a shorter median delay to relapse (7 vs 12.2 months, p=0.06) and had a significantly shorter overall survival compared to patients with the two major alleles (5-year OS, 14% vs 26%, p=0.02). In the subset of CN-AML (n=113), the presence of at least one minor allele was also associated with a shorter median delay to relapse (6.9 vs 12.5 months, p=0.02) but only a trend regarding overall survival was observed (5-year OS, 17% vs 30%, p=0.1). In multivariate analysis considering age, WBC count, cytogenetics (favorable, intermediate and unfavorable categories) as covariates, WT1 SNP rs16754 status was found to be an independent prognostic factor for relapse risk (HR 1.56, 95% CI 1.06 to 2.30, p=0.03) and overall survival (HR 1.54, 95% CI 1.08 to 2.20, p=0.02). Thus, in our cohort of older AML patients, the minor allele of WT1 SNP rs16754 appears to confer a relatively poor prognosis, which is in contradiction to what has been reported so far. Overall, our data suggest that WT1 SNP rs16754 is an interesting marker that may contribute to refine prognosis in AML, at least in this age group of patients. Further investigations are needed to clarify the relationship between WT1 SNP rs16754 and treatment outcome in AML and elucidate the biological effects of this SNP. Disclosures:No relevant conflicts of interest to declare.

Decitabine for Older AML Patients: An Effective Therapy Associated with Short Hospitalization and No Invasive Fungal Infection.

AbstractAbstract 1063 Purpose:The treatment of older patients (pts) with acute myeloid leukemia (AML) continues to be controversial because of the lack of effectiveness and the toxicity of available therapies. We investigated the efficacy, toxicity, and factors predictive of response to decitabine as initial therapy in older pts with AML. Methods:This is the largest single institution, retrospective study for pts older than 60 years with either De novo AML or MDS related AML who were treated initially with IV decitabine 20 mg/m2 for 5 consecutive days of a 4-week cycle from 01/01/2005- 01/01/2010. Pts continued to receive decitabine until disease progression or an unacceptable adverse event occurred. Pts with secondary AML were excluded. Results:45 pts were treated. Median age 71 (range, 61–83). Males-27 (60%). Females-18 (40%). Caucasians-40 (89%). African-Americans- 4 (9%). Asian-1 (2%). De novo AML-24 (53%). MDS related AML-21 (47%). Karyotypes: poor-27 (60%), intermediate -10(22%), unknown-8(18%). Median presenting WBC's 2.8 k (range, 0.6–122.2) with 26.6% of WBC's > 10k. The best response to therapy was CR/CRi-13 (29%), Stable disease/ partial remission (SD/PR) - 22 (49%), progressive disease (PD) -10 (22%). Pts who achieved CR/CRi: De novo AML-8, MDS related AML-5, poor cytogenetics-6, unknown cytogenetics-4, intermediate cytogenetics-3, presenting WBC's <10k-9, presenting WBC's >10k-4. Median number of cycles for CR/CRi was 4 (range, 1 to 5 cycles). Median number of cycles for CR/CRi was 4 in pts with presenting WBC's <10k and 4.5 in pts with presenting WBC's> 10k. 2 pts in CR/CRi group underwent consolidative BMT while on decitabine. The median duration of CR/CRi was 393 days (range, 184–748). The median time from first cycle till plt count recovery was 49 days (range, 0–294). Plt count recovery was the first hematological sign for CR preceding bone marrow biopsy confirmation in 10 out13 pts (77%). Plt count recovery on day 90 of therapy was achieved in 18 pts (40%) of whom 9 out of 18 achieved CR. The median overall survival (OS) from the time of diagnosis was 8.75 months (mo) (range, 0.5–59.8), CR/CRi-18.9 mo (range, 7.8–37.9), SD/PR-7.3 mo (range, 1.9–59.8), PD-1.9 mo (range, 0.5–12.1). Median OS for pts presented with WBC's< 10k was 11.0 mo (range, 0.5–59.8) and WBC's >10k was 7.1 mo (range, 1.9–32.7). In CR/ Cri group, the median OS for pts presented with low and high WBC's was 19.2 mo (range, 10–37.9) and 11.2 mo (range, 10.5–32.7) respectively. The 30, 60, and 100 day mortality rates after first cycle of therapy were (6/45)13.3%, (9/45) 20%, and (10/45) 22.2% respectively. The mean number of days for hospitalization while on decitabine was 19.2 days (range, 0–59), CR/CRi 14.3 days (range, 0–59), SD/PR 19.4 days (range, 0–54), PD 25.3 days (range, 5–52). 28 culture documented infection events noted in all groups: CR /CRi-5, SD/PR-22, PD-1. Staph species 14 events, Pseudomonas Aeruginosa 4 events, E-coli 3 events, C. difficile 2 events, candida species 2 events, and 1 event for each of: bacillius species, achromobacter, and enterobacter cloacae. No documented invasive fungal infections were seen. Bleeding events were observed in 3 pts (2 gastrointestinal and 1 fatal SDH due to fall). Salvage therapy was offered to 10 pts after decitabine failure (5 in CR/CRi group, 4 in SD/PR group and 1 in PD group). Different salvage regimens used including idarubicine + cytarabine (5), FLAG (1), SAHA (3), PXD 101 (1), and Gemtuzumab (1). CR was achieved in 3 out of 4 pts who received 7+3 all in CR/CRI group. Univariate analysis of factors predictive of CR and Survivals are shown in table 1.Table 1VariableP Value for CRP Value for survivalAge at Diagnosis0.27430.3431Sex0.89060.6491De Novo vs MDS related0.28460.6174Karyotypes: others vs poor0.22560.0465Presenting WBC's > or < 10k0.54360.2386Multivariate analysis for factors predictive of survival was significant for intermediate risk cytogenetics with P value of 0.0410. Conclusion:Decitabine resulted in CR/CRi in 29% of pts after a median of 4 cycles of therapy. Median duration of CR was 393 days. The mean duration for hospital stay was 19.2 days. No documented invasive fungal infections seen and 1 fatal bleed reported. Disclosures:No relevant conflicts of interest to declare.

Estimating the Chances of Older AML Patients to Achieve a Complete Remission Upon Intensive Induction Chemotherapy - An AMLCG and SAL Study

AbstractAbstract 2696 Introduction:The prognosis of older patients (≥ 60 years) with acute myeloid leukemia (AML) is generally poor. The decision whether or not to use intensive chemotherapy in this patient cohort is challenging since only half of all older AML patients will eventually achieve a complete remission (CR) with an intensive approach. We therefore sought to develop a clinically relevant risk score for estimating the chance to obtain a CR compared to the risk of early death (ED). Patients and Methods:1406 patients ≥ 60 years of age with AML and evaluable for an induction result after treatment with an intensive induction regimen (1-2 courses of either standard-dose araC containing TAD - high-dose araC containing HAM or HAM - HAM) within the AMLCG1999 study of the German AML Cooperative Group (AMLCG) were analyzed. External validation was performed on 801 patients ≥ 61 years of age treated in the AML96 study of the Study Alliance Leukemia (SAL) treated with 1–2 courses of a ‘7+3‘ induction. 16 clinical parameters as well as cytogenetic and molecular risk factors were evaluated for risk prediction in an exploratory analysis. Results:Among the analyzed parameters, age, de novo versus secondary leukemia, body temperature, hemoglobin, thrombocyte count, LDH, fibrinogen and the cytogenetic and molecular risk were significantly associated with a CR and/or with an ED within 60 days (p<0.05) in a multivariate logistic regression analysis. For comparison, patients were grouped into quarters by their predicted CR and ED score. The comparison of the predicted with the observed CR and ED rates within these quarters and additionally within the highest and lowest 5% showed a valid prediction of the CR and ED rates by the individual risk prediction (figure 1A & B). This could also be demonstrated when applying these CR and ED scores on an independent patient population (figure 1C &D). Conclusions:These scores based on pretreatment clinical, cytogenetic and molecular variables provide a reasonable estimate for CR and the ED rate of elderly AML patients. An online calculation tool for the prediction of the CR and the ED rate has been implemented (www.aml-score.org). This tool might be helpful to determine the treatment strategy for older patients with AML. [Display omitted] Comparison of the predicted CR and ED rate with the corresponding observed CR and ED rates. Patients were grouped into quarters by their predicted CR or ED rates and the boxplot of the predicted rate of each quarter is plotted against the observed rate of this quarter. In addition, the predicted versus the observed rates of the extreme 5% by predicted rates are shown. A: AMLCG population, CR rates; B: AMLCG population, ED rates; C: SAL population, CR rates; D: SAL population, ED rates. Disclosure:Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership, Research Funding.

Treatment of older patients with de novo acute myeloid leukemia (AML) with one or more postremission chemotherapy courses: Analysis of four CALGB studies.

6531 Background: AML in older patients is rarely cured by chemotherapy, but treatment is given to induce complete remission (CR) and prolong disease-free and overall survival (DFS, OS). Optimal post-CR chemotherapy has not been defined. We analyzed outcomes in previously untreated de novo AML patients ≥ 60 years (n = 1,525) among 4 consecutive CALGB trials using different consolidation regimens. A randomized trial (8923) produced similar results using 2 courses of cytarabine (AraC) 1 g/m2 x 5 days plus mitoxantrone 10 mg/m2 x 3 days compared to 4 courses of AraC at 100 mg/m2 x 5 days (Blood 2001;98:548). CALGB 9720 used ADE induction (AraC 100 mg/m2, daunorubicin 60 mg/m2 and etoposide 100 mg/m2 for 7, 3 and 3 days) with only a single post-remission course of the same drugs and doses for 5, 2 and 2 days. Methods: Results of 9720 were compared with results from similar patient populations treated on 3 other CALGB trials that used more than one post-CR course – either 4 courses (8525, 8923) or 2 intensified courses (8923, 10201). Results: The CR rate on 9720 did not differ compared to the other trials (52 vs. 53%), but DFS was significantly shorter (medians, 7.0 vs. 9.3 mos; p = 0.002), while OS did not differ (median, 8.4 mos), nor did survival following attainment of CR (13.9 vs. 14.5 mos; p = 0.13). DFS was shorter on 9720 for patients both 60-69 (n = 480; 6.9 vs. 9.3 mos; p = 0.02) and 70-79 (n = 294; 7.4 vs. 10.3 mos; p = 0.04) years; there were too few CR patients ≥ 80 years (n = 20) to allow a reliable conclusion. Conclusions: This historical comparison suggests that a single consolidation course results in significantly shorter DFS for de novo AML patients ≥ 60 years, but has no effect on OS nor survival following attainment of CR. The value of administering additional consolidation courses to prolong DFS without an effect on OS is debatable. Outcomes within cytogenetic and molecular subsets as well as quality of life measurements would be of interest. DFS and OS have remained short among older AML patients over the 25-year period covered by these studies; experimental approaches, including nonmyeloablative allogeneic hematopoietic cell transplantation in appropriate patients, are thus warranted. No significant financial relationships to disclose.

Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study

AbstractIn older patients with acute myeloid leukemia (AML), the prevention of relapse has remained one of the major therapeutic challenges, with more than 75% relapses after complete remission. The anti-CD33 immunotoxin conjugate gemtuzumab ozogamicin (GO) has shown antileukemic remission induction activity in patients with relapsed AML. Patients with AML or refractory anemia with excess blasts in first complete remission attained after intensive induction chemotherapy were randomized between 3 cycles of GO (6 mg/m2 every 4 weeks) or no postremission therapy (control) to assess whether GO would improve outcome. The 2 treatment groups (113 patients receiving GO vs 119 control patients) were comparable with regard to age (60-78 years, median 67 years), performance status, and cytogenetics. A total of 110 of 113 received at least 1 cycle of GO, and 65 of 113 patients completed the 3 cycles. Premature discontinuation was mainly attributable to incomplete hematologic recovery or intercurrent relapse. Median time to recovery of platelets 50 × 109/L and neutrophils 0.5 × 109/L after GO was 14 days and 20 days. Nonhematologic toxicities were mild overall, but there was 1 toxic death caused by liver failure. There were no significant differences between both treatment groups with regard to relapse probabilities, nonrelapse mortality, overall survival, or disease-free survival (17% vs 16% at 5 years). Postremission treatment with GO in older AML patients does not provide benefits regarding any clinical end points. The HOVON-43 study is registered at The Netherlands Trial Registry (number NTR212) and at http://www.controlled-trials.com as ISRCTN77039377.

Levels of Care: Defining Best Supportive Care in Elderly Patients with Acute Myeloid Leukemia

This article reviews published data on best supportive care (BSC) in older patients with acute myeloid leukemia (AML) and proposes improvements in defining this critical aspect of treatment. A clinical challenge is to prospectively identify patients who could benefit from existing therapies and to optimize their treatment tolerance by improving BSC. Advanced age and poor performance status consistently emerge as reliable indicators of poor outcome in older AML patients and have historically been the most important variables used to stratify treatment. Performance status is notoriously difficult to assess, and a "snapshot" view at the time of initial presentation can be misleading. Comorbidity scales may be a better predictor of outcome, but studies looking at their effectiveness are variable. New methods are needed to stratify patients. Although the prognosis of older AML patients is generally dismal, selected patients benefit from treatment and can have prolonged survival. Because it has never been shown that BSC as a sole therapeutic approach is kinder, less expensive, or better for older AML patients, it should be reserved for select clinical situations.

Decitabine Can Induce Complete Cytogenetic Responses When Used as Initial Therapy in Older AML Patients.

Abstract 4123 Background The incidence of acute myeloid leukemia (AML) increases with advancing age. At present, there are limited treatment options available for older patients because of lack of efficacy and increased toxicity. In a previously reported Phase II AML trial (n = 55), older patients not previously treated for AML experienced an overall response rate of 25% with decitabine (Cashen et al. Blood 2008). Response rate was similar in patients with poor or intermediate cytogenetic risk at baseline. In addition, 5 (15%) of the 34 patients who had cytogenetic abnormalities at baseline achieved a complete cytogenetic response in this trial. As older AML patients are more likely to present with unfavorable cytogenetic profiles, it was of interest to review the patient characteristics and describe the responses of the 5 patients who had a complete cytogenetic response. Methods The patients for this analysis were from a multicenter, Phase II study. In this study, patients over the age of 60 with AML (&gt;20% bone marrow blasts) and no prior therapy for AML were treated with decitabine, 20 mg/m2 IV for 5 consecutive days of a 28-day cycle until disease progression or unacceptable adverse event. Cytogenetic profile was assessed at screening and after every cycle, beginning with cycle 2. Results The 5 patients (2 males, 3 females; 5 white; 2 M1, 1 each for M2, M6, and M7) with a complete cytogenetic response had baseline characteristics that are associated with high risk. Three were &gt;70 yrs of age, and all 5 had AML secondary to prior therapy (n=2) or MDS (n=3). Four patients had poor-risk cytogenetics: 2 pts with -7, -5q, and ≥ 3 abnormalities and 2 pts with deletions of chromosome 5 and ≥ 3 abnormalities. One patient had intermediate-risk cytogenetics. The median baseline bone marrow myeloblast count was 33% (range 21 to 60). These patients were treated with a median 10 cycles (range 6 to 19) of decitabine. The median time to a complete cytogenetic response was 5 cycles (range 2.3 to 6). The median time to relapse from a complete cytogenetic response was 8.1 cycles (range 3.4 to 19.8). The overall median survival was 21.6 months (95% CI: 9.5, 24.7), which compares favorably to the median overall survival of the entire study cohort (21.6 months vs. 7.7 months, Cashen et al. Blood 2008). Conclusions Treatment with decitabine can induce complete and durable cytogenetic responses, even in older patients with high risk disease characteristics and poor risk cytogenetics. Patients who achieve a cytogenetic response may have a survival benefit. A presently ongoing Phase III survival trial with decitabine will help further characterize the effect of decitabine on cytogenetic responses in older AML patients. Disclosures: Cashen: Eisai, Inc.: Consultancy.

Allogeneic Hematopoietic Stem Cell Transplantation (HCT) Compared to Chemotherapy Only in Acute Myeloid Leukemia (AML) Patients 60 Years and Older: A Center for International Blood and Marrow Transplantation Research (CIBMTR)/ Cancer and Leukemia Group B (CALGB) Study.

Abstract 657The outcome of patients aged 60 years or older with AML treated with conventional cytotoxic chemotherapy remains extremely poor with few long-term survivors, irrespective of the type of induction or post-remission treatment intensity or duration. In younger patients, allogeneic HCT performed in first complete remission (CR1) appears to offer a potential advantage in terms of progression-free survival and possibly overall survival (OS) in patients with adverse prognostic features, due at least in part to a graft-versus-leukemia (GvL) effect. Preliminary results of reduced-intensity (RIC) allogeneic HCT performed in older AML patients in CR1 suggest that this approach may improve long-term outcome. However, as patients undergoing allogeneic HCT are likely to be highly selected, it remains uncertain if such an approach will truly improve outcome compared to chemotherapy alone. To investigate this possibility, we compared the outcome of 100 AML patients aged 60-70 years who received RIC allogeneic HSCT in CR1 and were reported to the CIBMTR to that of 96 AML patients treated with only standard induction (daunorubicin and cytarabine ± etoposide) and post-remission chemotherapy on CALGB protocols 9720 and 10201 between January 1998 and October 2006. Patients with therapy-related AML or following an antecedent hematologic disorder were included, along with de novo patients. In the chemotherapy-treated group, only patients who remained in CR1 for at least 4 months were included in order to reduce selection bias. Patients in the HCT cohort were younger than those in the chemotherapy-treated cohort (P<.001; median age 63 v 65 years). There was no significant difference in the distribution of sex, therapy-related leukemia, white blood cell count, FAB classification, or the proportion with normal cytogenetics at diagnosis between the two groups. The time from diagnosis to achievement of CR1 was longer for HCT patients compared to chemotherapy-treated patients (P=.007; median 46 v 38 days). HCT donors were HLA-identical siblings (n=48, 48%) and closely matched unrelated donors (n=52, 52%) and all HCT utilized reduced intensity conditioning plus pharmacologic GVHD prophylaxis. The median follow-up of chemotherapy-treated patients was longer than that of HSCT patients (51 v 30 months). Overall, allogeneic HCT tended to be associated with longer leukemia-free survival (LFS) compared to chemotherapy. The 3-year LFS from CR1 for HCT patients was 34% (95% confidence interval [CI], 24%-44%) compared to 17% (95% CI, 10%-25%) for chemotherapy-treated patients (P=.06). This was largely due to a higher relapse rate (RR); 86% of the chemotherapy patients relapsed compared to only 29% who received HCT (P<.001). However, the non-relapse mortality rate was significantly higher among patients receiving HCT compared to chemotherapy-treated patients (P<.001; 39% v 17%). Survival from CR1 did not differ between the groups (P=.47), with 3 year estimates of 35% (95% CI, 25%-46%) for HSCT patients compared to 25% (95% CI, 17%-34%) for chemotherapy patients. Our results indicate that RIC allogeneic HCT in CR1 in older AML patients is associated with a longer LFS, largely due to a reduction in the RR. Strategies aimed at reducing non-relapse mortality associated with allogeneic HCT, including better graft-versus-host disease prophylaxis and treatment, may lead to a significant improvement in OS for older AML patients. Disclosures:No relevant conflicts of interest to declare.

A Novel Risk Score Predicts the Likelihood of a Complete Remission After Intensive Induction Therapy in Older AML Patients.

Abstract 327▪▪This icon denotes an abstract that is clinically relevant. Introduction:Older patients (≥ 60 years) with acute myeloid leukemia (AML) display a dismal prognosis with only half of the patients reaching a complete remission after intensive induction therapy. The decision whether or not to use intensive chemotherapy is often difficult given the limited number of known markers that might predict the chance to achieve a complete remission. The aim of this study was to establish a risk score for therapy-failure based on clinical variables for older but medically fit AML patients. Patients and Methods:1379 patients ≥ 60 years of age with AML evaluable for an induction result after treatment with an intensive induction regimen (randomized standard-dose cytarabine containing TAD or high-dose cytarabine (1g/sqm × 6) containing HAM, with a second induction course HAM in case of blast persistence after the first course) within the AMLCG1999 study of the German AML Co-operative Group were evaluated. The following parameters were evaluated for risk prediction in an exploratory analysis: Age, sex, de novo versus secondary leukemia, performance status, body mass index, body temperature, presence of extramedullary manifestations, spleen size, presence of lymph node enlargement, hemoglobin, peripheral blood leukocytes, platelets, blast percentage in peripheral blood and bone marrow, total protein in serum, alanine aminotransferase (ALT), alkaline phosphatase (AP), bilirubin, lactate dehydrogenase (LDH), FAB classification, prothrombin time (PT) and fibrinogen. Since cytogenetics and molecular markers are often not available at the time of decision making, these data were not included. Results:Within this cohort of patients, 744 (54 %) achieved a complete remission. Among the analyzed parameters, age, de novo versus secondary leukaemia, body mass index, body temperature, hemoglobin, peripheral blood leukocytes, platelets, bone marrow and peripheral blood blasts, ALT, AP, LDH, PT and fibrinogen were significantly associated with a CR (p<0.05) in a univariate log rank analysis. In a multivariate logistic regression model, the following parameters retained its significance: age (60 – 63 years, 64 – 67 years, 68 – 72 years, ≥ 73 years) de novo versus secondary leukemia, body temperature (≤ 36°C, > 36°C – 38°C, > 38°C), hemoglobin (≤ 10.3 g/dl versus > 10.3 g/dl), platelets (≤ 28,000, > 28,000 - 53000, > 53,000 – 103,000, > 103,000 per μl), AP (≤ 89 U/l versus > 89 U/l), PT (≤ 75 %, > 75 – 87 %, > 87 – 98 %, > 98 %) and fibrinogen (≤ 150 mg/dl versus > 150 mg/dl). Based on these parameters, the predicted remission rates were: minimum, 18.3 %; 1st quartile, 43.9 %; median, 54.4 %;3rd quartile, 64.3 %; maximum: 88.1 %. The observed remission rates were: 1st quarter, 35.7 %; 2nd quarter, 50.3 %; 3rd quarter, 60.2 %; 4th quarter, 69.8 %. Conclusions:Taken together, this risk prediction score based on pre-treatment values predicted the remission probability in patients ≥ 60 years of age with AML receiving an intensive induction therapy. This score may be useful for the determination of the therapy strategy in elderly patients with AML. Disclosures:No relevant conflicts of interest to declare.