ALBERT

Description: Additive manufacturing (AM) is a rapidly growing field of technology. In order to increase the variety of metal alloys applicable for AM, selective laser melting (SLM) of duplex stainless steel 2205 powder and the resulting microstructure, density, mechanical properties, and corrosion resistance were investigated. An optimal set of processing parameters for producing high density (〉99.9%) material was established. Various post-processing heat treatments were applied on the as-built predominantly ferritic material to achieve the desired dual-phase microstructure. Effects of annealing at temperatures of 950 °C, 1000 °C, 1050 °C, and 1100 °C on microstructure, crystallographic texture, and phase balance were examined. As a result of annealing, 40–46 vol.% of austenite phase was formed. Annealing decreased the high yield and tensile strength values of the as-built material, but significantly increased the ductility. Annealing also decreased the residual stresses in the material. Mechanical properties of the SLM-processed and heat-treated materials outperformed those of conventionally produced alloy counterparts. Using a scanning strategy with 66° rotation between layers decreased the strength of the crystallographic texture. Electrochemical cyclic potentiodynamic polarization testing in 0.6 M NaCl solution at room temperature showed that the heat treatment improved the pitting corrosion resistance of the as-built SLM-processed material.

Description: Abstract Ice crystals form in supercooled seawater beneath several Antarctic ice shelves; as they rise to the ice‐shelf base they scavenge particles from the water and incorporate them into the growing basal ice. The resulting marine ice can be ~100 m thick; it differs from sea ice in that it is clear, desalinated, and bubble‐free. Icebergs of marine ice vary in color from blue to green, depending on the nature and abundance of foreign constituents in the seawater that became trapped in the ice as it grew. A red or yellow material (i.e., one that absorbs blue light), in combination with the blue of ice, can shift the wavelength of minimum absorption to green. Previously, dissolved organic carbon (DOC) had been proposed to be responsible for the green color. Subsequent measurements of low DOC values in green icebergs, together with the recent finding of large concentrations of iron in marine ice from the Amery Ice Shelf, suggest that the color of green icebergs is caused more by iron‐oxide minerals than by DOC. These icebergs travel great distances from their origin; when they melt they can deliver iron as a nutrient to the Southern Ocean.

Description: INTRODUCTION: Most clinical trials exclude patients with poor performance, organ dysfunction, and presence of other active malignancies or comorbidities. Although some of these criteria are based on clinical reasoning, patients with such clinical features have dismal expected outcomes and limited therapeutic options and could therefore have a more favorable risk/benefit ratio if treated with a low intensity investigational intervention. The current study was designed to test whether it is feasible to treat patients not eligible for conventional studies in a clinical trial. METHODS: We conducted an initial Bayesian designed single-arm study and a subsequent randomized study for patients with AML or higher-risk MDS (intermediate-2 or high risk by IPSS) with either ECOG performance status (PS) ≥3, creatinine or bilirubin ≥2mg/dL, presence of other malignancy or other comorbidities. Primary endpoint was survival at day 60. The study included stopping rules for survival, response and toxicity. All patients received azacitidine 75mg/m2 sc daily for 5 days. Patients in the single-arm study and in the combination arm of the randomized study also received vorinostat 200mg tid for 5 days. Cycles could be repeated every 3-8 weeks. Responses were evaluated following the revised 2006 IWG criteria for patients with MDS and the IWG 2003 recommendations for patients with AML. Comorbidities were evaluated using the Adult Comorbidity Evaluation-27 (ACE-27) index. Adverse events (AEs) were assessed and graded according to the CTCAE v4 criteria. Overall survival (OS) was censored at the time of transplant. Event-free survival (EFS) was defined as the time interval between treatment start and date of resistance, progression or death. RESULTS: A total of 30 patients (16 with MDS, 14 with AML) were enrolled in the initial single-arm study. Patient characteristics and inclusion criteria are detailed in Table 1. Median age was 73 years (44-83). Median follow-up was 7.4 months (0.3-29). Sixty-day survival was 83%. Median number of cycles administered was 3.5 (1-12). The overall response rate (ORR) was 40% with 8 (27%) patients achieving CR, 4 with AML and 4 with MDS. Median OS was 7.8 months (0.3-29, CI 7.54-8.03) (Figure 1A) and median EFS was 5.1 months (0.3-15.9, CI 4.87-5.37) (Figure 1B). Stopping rules for survival and response were not met. Main adverse events (AEs) where grade 1-2 gastrointestinal toxicities. Mortality at 4 and 8 weeks was 10 and 20% respectively. A total of 79 patients were enrolled in the subsequent randomized study: 27 to azacitidine (A) and 52 to azacitidine and vorinostat (A+V). Patient characteristics and inclusion criteria are also shown in Table 1. Median age was 70 years (30-90). Forty-seven (59%) patients had MDS and 32 (41%) had AML. Median follow-up was 22.7 months (12.6-47.5). Sixty-day survival rates were 67% (A) and 85% (A+V), respectively (p=0.07). No differences in ORR (48% vs 46%, p=0.87), OS (6.1 vs 7.6 months, p=0.49) (Figure 1C) or EFS (3 vs 5.5 months, p=0.05) (Figure 1D) were observed between groups. Main AEs included grade 1-2 gastrointestinal toxicities with a higher proportion of AEs with A+V (81 vs 56%). Mortality at 4 and 8 weeks was 10% (A: 4, A+V: 4) and 19% (A: 9, A+V: 6) respectively. By univariate analysis neither PS ≥3, creatinine or bilirubin ≥2mg/dL nor presence of other malignancy were predictive for 60-day survival, OS or EFS. There were no significant differences in survival between patients with ACE-27 scores of 0-1 compared to 2-3 both in the single-arm (6.3 vs 7 months, HR=0.88, 95% CI 0.41-1.91, p=0.75) and the randomized phase of the study (A: 13.5m vs 6.1m, HR 0.93, 95% CI 0.27-3.17, p=0.9 and A+V: 12.1m vs 7.4m, HR 1.38, 95% CI 0.61-3.14, p=0.4). CONCLUSION: Most enrolled patients met the study's primary endpoint of survival at 60 days without major toxicity. Patients obtained clinical benefit with acceptable responses and survival despite their high comorbidity burden. Our results support the feasibility of treating patients with MDS or AML not eligible to other clinical trials due to poor performance status, comorbidities or organ dysfunction, with low intensity therapies within a clinical trial. These findings suggest relaxation of such criteria may likely increase the pool of clinical trial patient candidates and allow access to potential beneficial therapies for patients with otherwise dismal prognosis. Table 1 Table 1. Figure 1 Figure 1. Disclosures Jabbour: ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. DiNardo:Abbvie: Research Funding; Novartis: Research Funding; Agios: Research Funding; Daiichi Sankyo: Research Funding; Celgene: Research Funding. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. Wierda:Genentech: Research Funding; Gilead: Research Funding; Novartis: Research Funding; Acerta: Research Funding; Abbvie: Research Funding. Konopleva:Reata Pharmaceuticals: Equity Ownership; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Stemline: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding. Jain:Novimmune: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Abbvie: Research Funding; Infinity: Research Funding; Incyte: Research Funding; Seattle Genetics: Research Funding; BMS: Research Funding; Novartis: Consultancy, Honoraria; Servier: Consultancy, Honoraria.

Description: Abstract 1080 Background: The role of arsenic trioxide (ATO) in the frontline treatment of patients with acute promyelocytic leukemia (APL) remains unclear with a number of studies reporting high and durable responses with single agent ATO. We have conducted a trial combining all-trans-retinoic acid (ATRA) with ATO with or without gemtuzumab ozogamicin (GO) in patients with previously untreated APL. Patients and methods: From July 2002 to June 2010, 104 patients with newly diagnosed APL were treated with a combination of ATRA plus ATO in two studies. The first cohort of 47 patients received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily beginning on day 10 of ATRA). High-risk patients (White blood cell count [WBC] 〉 10 × 109/L) received GO 9 mg/m2 on the first day of induction. From July 2007, the second cohort of 57 patients received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily) concomitantly on day one of induction. They also received GO 9 mg/m2 on day 1, if high risk, and any time during induction if the WBC rose to 〉 30 × 109/L (and more recently if 〉 10 × 109/L). Monitoring for PML-RARA fusion gene using reverse transcriptase-polymerase chain reaction (RT-PCR) was conducted after induction and throughout consolidation and follow up. The median age for the 104 patients was 46 years (range, 14–81). Their median presenting WBC was 2.7 × 109/L (0.4-131.4 × 109/L) and their median platelet count was 36 × 109/L (range, 7–261 × 109/L). Seventy three (70%) had low risk and 31 (30%) high risk disease (based only on the presentation WBC ≤ or 〉 10.0 × 109/L). Results: Overall, 102 patients (98%) achieved complete remission (CR) and 2 died during induction. With a median follow-up of 115 weeks (range, 4 to 397 weeks), 94 patients remain alive. The estimated 5-year survival rate was 88% and event-free survival 86%; only 5 of the patients achieving a CR (5%) have relapsed. The median overall survival, remission duration and event-free survival have not been reached (Figure). Thirty six patients have been alive and in remission for more than 3 years and 21 for more than 5 years. Two late deaths (beyond 300 weeks) occurred in CR from unrelated causes. Conclusion: The combination of ATRA and ATO (with or without GO) as initial therapy for APL is highly effective and safe; it can potentially substitute for chemotherapy containing regimens in high and low risk patients. Disclosures: Ravandi: Cephalon: Honoraria, Research Funding, Speakers Bureau. Off Label Use: Off-label use of arsenic trioxide in frontline therapy of APL; off label use of gemtuzumab ozogamicin in APL. Verstovsek:Incyte Corporation: Research Funding.

Description: Abstract 1516 Background: Sorafenib is a potent inhibitor of FLT3 kinase with demonstrable clinical activity in patients with acute myeloid leukemia (AML) and FLT3-ITD mutation, but not those with FLT3-D835 mutation. Objectives: To determine the long term outcome of patients with AML treated with the combination of Sorafenib, cytarabine and idarubicin, and in particular those with FLT3-ITD mutation. Method: Between October 2007 to March 2010, 62 patients with newly diagnosed, previously untreated AML, were treated with Sorafenib 400 mg orally twice daily (BID) for 7 days, cytarabine 1.5 g/m2 by continuous intravenous (IV) infusion daily for 4 days (3 days if 〉 60 years of age), and idarubicin at 12 mg/m2 IV daily for 3 days on an IRB-approved clinical trial. After achieving remission, patients received up to 5 cycles of consolidation with sorafenib 400 mg BID continuously and abbreviated doses of cytarabine and idarubicin given at approximately one month intervals. Results: 62 patients were treated on the phase II portion of the study. Median age was 53 years (range, 18 – 66) and 12 (19%) patients were 〉 60 years. 23 (37%) had FLT3 mutations including 17 with FLT3-ITD, 4 with FLT3-D835, and 2 with both mutations. Cytogenetics was diploid in 36 (58%), chromosome 5 and 7 deletion in 4 (6%) and 1 (2%) respectively, complex in 8 (13%), miscellaneous in 13 (21%). Median white blood cell count (WBC) at diagnosis was 7.25 × 109/L (range, 0.6 – 225), and 28 (45%) patients had WBC 〉 10 × 109/L; among these, 12 (43 %) had FLT3-ITD. After induction, 49 (79 %) patients achieved CR and 5 (8%) CR with incomplete platelet recovery (CRp). 1 (2%) patient died before response assessment could be performed and 7 (11%) were non responders. Patients with FLT3-ITD were more likely to achieve a CR/CRp than patients without FLT3-ITD [18/19 (95%) patients vs. 36/43 (83%) patients, respectively (p=0.23)]. To date, 32 (59%) of the responders have relapsed including 10 of 18 (56%) patients with FLT3-ITD and 22 of 36 (61%) patients without FLT3-ITD (P=0.86). 35 patients received salvage therapy; 14 died after receiving salvage therapy, 11 achieved a second CR and 10 were refractory. After a median follow up of 40.6 months (range, 5.7 to 50 months), the median DFS and OS were 13 months and 29 months, respectively. Hematopoietic stem cell transplantation (HSCT) was performed in 34 (55 %) patients, including 23 in CR, and 11 with active disease. Stem cell source was from related donors in 15 (44%), unrelated donors in 9 (26%), cord blood in 7 (21%), and haploidentical donors in 3 (9%) patients. Overall, 35 (56%) patients have died; 16 (26%) had infectious complications, 12 (19%) multi-organ failure, 9 (15%) graft versus host disease, and 10 (16%) other causes with some patients having overlapping causes. Three-year disease free survival (DFS)(in patients achieving CR, n=54) and overall survival (OS) (n=62) were 34% and 47%, respectively (Figures 1 and 2). Conclusion: Combination of sorafenib, idarubicin and cytarabine is an effective regimen with durable responses in patients with newly diagnosed AML, particularly those with FLT3-ITD. Disclosures: Ravandi: Bayer: Research Funding; Onyx: Research Funding.

Description: Background Slow progress has been made in improving induction therapy for patients (pts) with AML. Nucleoside analogues such as cladribine can increase the efficacy of araC by modulating deoxycytidine kinase. Indeed, the addition of cladribine to standard 7+3 chemotherapy has been shown to improve survival in pts with AML (Holowiecki JCO 2012). Additionally, higher doses of araC during induction may have a role in improving outcomes for younger pts (Burnett JCO 2013, Willemze JCO 2013). We conducted a trial to study the efficacy of cladribine combined with higher-dose araC during induction for younger pts with AML. Methods The three-drug, induction-consolidation treatment protocol consisted of the combination of cladribine, idarubicin, and araC (CLIA) in pts with AML aged ≤ 65. Two cohorts were enrolled: newly diagnosed and relapsed/refractory (R/R). Pts with adequate organ function, a diagnosis of AML (except APL), including secondary- (s-AML) and therapy-related AML (t-AML), and high risk MDS were eligible. Induction consisted of cladribine 5 mg/m2 IV over 30 minutes on days 1-5, followed (3-6 hrs later) by araC 1000 mg/m2 IV on days 1-5, and idarubicin 10 mg/m2 IV days 1-3. Consolidation consisted of up to 5 more cycles of cladribine 5 mg/m2 IV over 30 minutes on days 1-3 with araC 750 mg/m2 IV on days 1-3 and idarubicin 8 mg/m2 IV on days 1-2. One cycle was 4 weeks and up to 2 cycles of induction were allowed. Pts with FLT3-ITD could have sorafenib 400mg PO BID added to CLIA. Pts with FLT3+ disease or presenting WBC count 〉 100 received prophylactic intrathecal araC at the nadir of their counts during cycle 1. AML mutation screening was performed prior to treatment. Results A total of 54 pts were enrolled, with a median age of 51 years (range, 20-65), including 24 pts (44%) in the frontline cohort and 30 (56%) in the R/R cohort. Patient characteristics by cohort are outlined in Table 1. In the frontline cohort, 24 pts, who received a median of 2 (1-6) cycles, were evaluable for response. Sixteen patients achieved CR (67%) after a median of 1 (1-4) cycle. The 4- and 8-week mortality rates were 0% and 4%, respectively. 2/4 (50%) pts with FLT3-ITD, 7/7 (100%) pts with NPM1, and 2/4 (50%) pts with RAS mutations achieved a CR. In the R/R cohort, 29 pts, who received a median of 1 (1-4) cycle, were evaluable for response. Six patients achieved CR (21%), 2 CRp (7%), and 4 CRi (14%), for an overall response rate (ORR) of 41%. A median of 1 (1-2) cycle was required for response. The 4- and 8-week mortality rates were 7% and 10%, respectively. Patients in the R/R cohort had received a median of 2 (1-5) prior therapies. ORR by salvage status is summarized in Table 2. 4/8 (50%) pts with FLT3-ITD, 4/8 (50%) pts with NPM1, and 1/3 (33%) pts with RAS mutations achieved a response (CR/CRp/CRi). With a median follow-up of 6 months (0.9 - 11.9), the 6-month OS estimates were 90% and 67% for the frontline and R/R cohorts, respectively (Figure 1). The 6-month remission durations were 100% and 79% for the frontline and R/R cohorts, respectively (Figure 1).The regimen was well tolerated. The most common ≥ grade 3 non-hematologic adverse events (AEs) were fever/infection (17), tumor lysis syndrome (1), cardiac arrhythmia (1), Rash (1), elevated bilirubin (1) and creatinine (1). Conclusion The 3-drug combination, CLIA, is safe and effective in patients with AML. Response rates for patients in the newly-diagnosed, first- and second-salvage settings are particularly interesting and should be explored further in larger studies and compared to current standard regimens.Table 1.CharacteristicParameterFrontlineSalvageAgeMedian (Range)52 (30 - 62)50 (20 - 65)DiagnosisAML [N]2430CytogeneticsDiploid, -Y ; N (%)13 (54)11 (37)Adverse ; N (%)4 (17)12 (40)Misc, other ; N (%)6 (25)7 (23)IM/ND ; N (%)1 (4)0 (0)Bone marrow Blast %Median (Range)50 (8 - 93)48 (10 - 94)WBC [x109/L]Median (Range)3.4 (0.7 - 37.9)2.9 (0.3 - 75.4)Platelets [x109/L]Median (Range)31 (12 - 584)19 (6 - 189)Peripheral Blood Blast %Median (Range)13 (1 - 91)48 (3 - 97)Serum CreatinineMedian (Range)0.71 (0.4 - 1.3)0.8 (0.5 - 1.4)LDHMedian (Range)568 (364 - 2449)792 (340 - 14159) Table 2. N ORR (%) CR (%) CRp (%) CRi (%) All Salvage 29 12 (41) 6 (21) 2 (7) 4 (14) 1st Salvage 9 6 (67) 4 (44) 1 (11) 1 (11) 2nd Salvage 8 4 (50) 2 (25) 0 (0) 2 (25) 3rd+ Salvage 12 2 (17) 0 (0) 1 (8) 1 (8) Figure 1. Figure 1. Disclosures Cortes: Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BerGenBio AS: Research Funding; Teva: Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy. Pemmaraju:Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. DiNardo:Novartis: Research Funding. Konopleva:Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding. Wierda:Celgene Corp.: Consultancy; Glaxo-Smith-Kline Inc.: Research Funding.

Description: Background: Imatinib induces durable complete cytogenetic remissions (CCyR) in at least two thirds of pts with chronic phase (CP) CML, most of them also achieving a major molecular response (MMR). However, some pts become intolerant or resistant to imatinib and require change of therapy to a 2nd or 3rd generation TKIs (dasatinib, nilotinib, bosutinib, and/or ponatinib). The projected 3-year survival for these pts was reported as 72% (Kantarjian et al. Cancer 2007) at a time when treatment options for such pts was limited. A smaller subset of pts may require additional changes to a third or fourth TKI. The impact of sequential TKI therapy, although standard practice, has not been well studied. We analyzed the long term outcome of pts receiving multiple TKIs. Method: We analyzed the medical records of 1775 pts with CML-CP treated at a single institution between 02/2000 and 07/2015. Among them 582 (33%) received more than one TKI as follows: 2TKIs (n=370), 3TKIs (n=130), and 4+TKIs (n=82; 4 TKI n=59, 5 TKI n=20, 6 TKI n=1, 7 TKI n=2). For the purpose of this analysis, a TKI used more than once was counted as 2 TKI provided there was a different TKI used between the two periods when the TKI in question was used. We analyzed pt's characteristics, response to therapy, transformation to accelerated and blast phase, and long term outcomes. Overall Survival (OS) and Transformation-Free Survival (TFS) probabilities were measured using Kaplan-Meier method starting from the date they began to use the their 2nd TKI and grouped by the number of TKI used. Results: The number of CML pts in early CP (diagnosis to start of therapy, ≤ 12 months) that used 2, 3, and 4+TKIs was 229, 54, and 34, respectively. The number of pts in late CP (diagnosis to start of therapy 〉12 months) that used 2, 3, and 4+TKIs was 141, 76 and 48 respectively. The median age (range) for pts that used 2, 3, and 4+ TKIs were 48 yrs (15-81), 52 yrs (18-87), and 53 yrs (18-80), respectively. The ratio of males to females in each cohort was 187:183, 58:72, and 37:45, respectively. The median time from diagnosis to 2nd, 3rd and 4th TKI was 2, 4, and 6 years respectively. For the 3 cohorts (2, 3, 4+TKIs), TKIs used included imatinib (n=322, n=130, n=79), dasatinib (n=227, n=112, n=77), nilotinib (n=119, n=109, n=70), ponatinib (n=44, n=27, n=37) and bosutinib (n=26, n=13, n=29), respectively. The 3-year overall survival probability for pts treated with 2 TKI was 88% (median survival not reached); for those that used 3 TKI 72% (median survival not reached), and for those that used 4+ TKI 48% (median survival 34 months) (Fig. 1). Corresponding 5-year figures are 80%, 53% and 38%. The 3-year transformation-free survival probability for pts treated with 2 TKI was 93%; for those treated with 3 TKI 88%; and for pts treated with 4 TKI 80% (median not reached in any cohort ) (Fig. 2). Corresponding figures for 5-years are 90%, 84%, and 75%. Conclusion: With more and improved treatment options, pts with resistance or intolerance to multiple TKI have the potential for long-term survival. Nearly 80% of pts who receive 2 TKI are alive at 5 years and more than 90% remain in chronic phase. As pts experience subsequent failure, the outcome worsens. These results provide information that may help with treatment planning and set the expectations against which treatment options used in such pts should be measured. Figure 1. Overall Survival Probability Figure 1. Overall Survival Probability Figure 2. Transformation-Free Survival Probability Figure 2. Transformation-Free Survival Probability Disclosures Wierda: Glaxo-Smith-Kline Inc.: Research Funding; Celgene Corp.: Consultancy. Daver:ImmunoGen: Other: clinical trial, Research Funding. Burger:Pharmacyclics LLC, an AbbVie Company: Research Funding. Pemmaraju:Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. Cortes:Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BerGenBio AS: Research Funding; BMS: Consultancy, Research Funding; Teva: Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy.

Description: We conducted this study to determine the feasibility and safety of cladribine followed by rituximab in patients with hairy cell leukemia including the vari-ant form (HCLv). Cladribine 5.6 mg/m2 given IV over 2 hours daily for 5 days was followed ∼ 1 month later with rituximab 375 mg/m2 IV weekly for 8 weeks. Responses were recorded and BM minimal residual disease (MRD) was evaluated after the completion of rituximab. Thirty-six patients have been treated including 5 with HCLv. Median age was 57 years (range, 37-89). All patients (100%) have achieved complete response (CR), defined as presence of no hairy cells in BM and blood with normalization of counts (absolute neutrophil count [ANC]〉 1.5 × 109/L, hemoglobin [Hgb] 〉 12.0 g/dL, platelets [PLT] 〉 100 × 109/L), as well as resolution of splenomegaly. There were no grade 3 or 4 nonhematologic adverse events directly related to the treatment. Only 1 patient (with HCLv) has relapsed; median CR duration has not been reached (range,1+-63+ months). Three patients with HCLv died including 1 with relapsed disease and 2 from unrelated malignancies. Median survival duration has not been reached (range, 2+-64+ months). Treatment with clad-ribine followed by rituximab is effective tk;4and may increase CR rate. This study was registered at www.clinicaltrials.gov as NCT00412594.

Description: Age affects the treatment outcome in adults with acute myeloid leukemia (AML) but its effect in pediatric AML is less certain. We reviewed outcome in 423 patients, 21 years of age or younger, who were treated for newly diagnosed AML (excluding acute promyelocytic leukemia) at St. Jude Children’s Research Hospital (n=288) or M.D. Anderson Cancer Center (n=135) between 1983–2002. Patients were divided into those treated between 1983–1989 and 1990–2002. During these two time periods, distinct sets of protocols were used in both institutions, with higher intensity treatment used in the more recent era. After accounting for the effects of cytogenetics, Down syndrome (favorable), increased WBC (unfavorable), FAB type M7 (unfavorable) and early treatment era (unfavorable), every additional year of age conveyed a 4.4 % increase in the risk of death and a 3.3% increase in the risk of any adverse event (death, failure to achieve complete remission, or relapse), with p〈 0.001 for the effect of age on survival or event-free survival (EFS). When patients were divided into those above or below the median age (10 years), there was a significant interaction between age and treatment era (p=.05), with patients below 10 having better EFS when treated in the recent era. For patients below 10, the relative risk of an event was 1.6 folds higher in the early treatment era than in the recent era ( p=.016). For patients 10 and older, the improvement in EFS according to treatment era was not significant. Treatment site did not influence the EFS or survival, and the effects of age were similar at both sites. These results suggest that age is an independent prognostic factor in childhood AML with younger children benefiting from more intensive treatment than their older counterparts.

Description: Background Treatment of AML in older patients is often complicated by poor tolerance to intensive chemotherapy, high early mortality, and resistant disease. Lower intensity approaches employing more active combinations are needed. Cladribine has been shown to have single-agent activity in AML, and to modulate deoxycytidine kinase, making ara-C more effective. Cladribine has recently been shown to improve survival when combined with standard-dose araC (Holowiecki JCO 2012). Methods We designed a low-intensity, prolonged-maintenance program investigating the combination of cladribine and low-dose araC (LDAC) alternating with decitabine in patients aged 〉 60. Patients with adequate organ function and newly diagnosed AML (except APL), including secondary- (s-AML) and therapy-related AML (t-AML), and high risk MDS were eligible. Induction consisted of cladribine 5 mg/m2 IV over 1-2 hours on days 1-5 followed by araC 20mg SQ BID on days 1-10. Consolidation/maintenance consisted of 2 cycles of cladribine 5 mg/m2 IV over 1-2 hours on days 1-3 + araC 20 mg SQ BID on days 1-10 alternating with 2 cycles of decitabine 20 mg/m2 on days 1-5, for a maximum of 18 cycles. One cycle was 4 weeks and up to 2 cycles of induction were allowed. Results Forty-five patients have been enrolled thus far with a median age of 69 years (range, 60-85), including 20 pts (44%) ≥ age 70. 20 pts (44%) had secondary- (s-AML) or therapy related AML (t-AML), 8 pts (18%) had therapy for an antecedent hematologic disorder, and 4 pts (9%) had a concurrent active second malignancy while on study. Patient characteristics are listed in table 1. Of the 36 pts evaluable for response, there were 21 CR (58%), 1 CRi (3%), and 2 PR (6%) for an overall response rate of 67% (24/36). 38% of patients (5/13) with an abnormal karyotype at the start of therapy achieved a complete cytogenetic response (CyR) and 1 (8%) had partial CyR at the time of CR. MRD negativity by flow cytometry was achieved in 12/23 pts (52%) in whom it was measured at the time of CR. All 5 patients (100%) with FLT3+ AML achieved a CR/CRi (4CR, 1CRi). With a median followup of 3.2 months, median OS and median CR duration have not been reached. (Figure 1) The 1-year OS estimate is 51%. The regimen was very well tolerated, with 0% 4-week mortality. There were no treatment-related grade 3/4 non-hematologic adverse events (AEs). Most common non-heme AEs were elevated bilirubin, constipation, nausea/vomiting, mucositis, diarrhea and rash. Conclusion The low intensity induction/consolidation/maintenance program of cladribine+LDAC alternating with decitabine is a highly effective, well-tolerated ambulatory regimen for older patients, including those with unfavorable-risk features. The study continues enrollment and updated data will be presented. Disclosures: No relevant conflicts of interest to declare.