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Background: Ponatinib is a potent, third-generation inhibitor of BCR-ABL that is active against T315I mutations of the ABL1 gene; these mutations are a common mechanism of resistance to earlier-generation BCR-ABL tyrosine kinase inhibitors (TKIs). Promising early efficacy of the combination of chemotherapy plus ponatinib has been reported in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), although long-term safety and durability of responses is less well-established. Methods: Adults with newly diagnosed Ph+ ALL and those who had received ≤2 courses of prior chemotherapy with or without TKIs were eligible. Patients (pts) received 8 cycles of hyper-CVAD alternating with high-dose methotrexate/cytarabine approximately every 21 days. Initially, ponatinib was given at 45 mg daily for the first 14 days of cycle 1 then continuously for the subsequent cycles. Rituximab was administered during the first 4 cycles in pts with CD20 expression ≥ 20%; pts also received 12 doses of prophylactic intrathecal chemotherapy with alternating methotrexate and cytarabine. Pts in complete remission (CR) received maintenance with ponatinib daily with vincristine/prednisone monthly for 2 years, followed by ponatinib indefinitely. Due to concern for vascular toxicity with long-term use of high-dose ponatinib, the protocol was amended after 37 pts were treated; this amendment reduced ponatinib to 30 mg starting at cycle 2 with further reduction to 15 mg once a complete molecular response (CMR) was achieved. The primary endpoint for the study was event-free survival (EFS); secondary endpoints included response rates, overall survival (OS), and safety. Results: The baseline characteristics of the 86 treated pts are shown in Table 1. The median age was 46 years (range, 21-80). Twenty pts (23%) were ≥60 years of age. Thirty-nine pts (45%) had at least one baseline cardiovascular risk factors (hypertension, diabetes, dyslipidemia, coronary artery disease, and/or peripheral arterial disease). Of 68 pts with active disease at enrollment, all pts achieved CR. The 3-month CMR rate was 74%, and overall CMR rate was 84%. There were no early deaths. Eighteen pts (21%) underwent hematopoietic stem cell transplantation (HSCT) in first remission. With a median follow-up of 43 months (range, 2-92 months), 61 pts (71%) remain alive in remission. The 3-year continuous CR, EFS and OS rates were 84%, 70%, and 78%, respectively, and estimated 5-year continuous CR, EFS and OS rates were 84%, 68%, and 73%, respectively (Figure 1A-B). Eleven pts (13%) relapsed after a median of 20 months in remission (range, 5 to 64 months). Six pts relapsed while on another TKI, 2 pts while not on a TKI, and 3 pts while still on ponatinib. Of the 3 relapses on ponatinib, 2 pts were found to have an E255K ABL1 kinase domain mutation and 1 pt had no mutation identified. A 6-month landmark analysis showed a trend for better OS in pts who did not undergo HSCT in first remission. The 3-year OS rate was 66% for pts who underwent HSCT (n=18) and 90% for pts who did not undergo HSCT (n=57; P=0.07). The treatment was overall well-tolerated with most adverse events being Grade 1-2. Overall, 37% of pts required dose reductions of ponatinib due to adverse events; the most common causes included rash (n=7), liver function test abnormalities (n=5), pancreatitis (n=3), deep vein thrombosis (n=2), and thrombocytopenia (n=2). Nine pts (10%) died in CR. Two ponatinib-related deaths from myocardial infarction were observed in pts treated before the protocol amendment to use lower doses of ponatinib; no further ponatinib-related deaths occurred after this amendment. Conclusions: In pts with newly diagnosed Ph+ ALL, the combination of hyper-CVAD plus ponatinib resulted in sustained responses with a CMR rate of 84% and an estimated 5-year OS rate of 73%. Among pts who did not undergo HSCT in first remission, the 3-year OS rate was 90%. Future studies are needed to determine whether the incorporation of effective novel agents such as blinatumomab into frontline regimens will allow for reduction of chemotherapy while also deepening responses and increasing the proportion of pts with Ph+ ALL who are cured without need for HSCT. Disclosures Short: AstraZeneca: Consultancy; Amgen: Honoraria; Takeda Oncology: Consultancy, Research Funding. Kantarjian:Novartis: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Research Funding; Immunogen: Research Funding; Amgen: Honoraria, Research Funding; Takeda: Honoraria; AbbVie: Honoraria, Research Funding; Agios: Honoraria, Research Funding; Ariad: Research Funding; Astex: Research Funding; Cyclacel: Research Funding; BMS: Research Funding; Daiichi-Sankyo: Research Funding; Pfizer: Honoraria, Research Funding. Ravandi:Selvita: Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cyclacel LTD: Research Funding; Macrogenix: Consultancy, Research Funding; Menarini Ricerche: Research Funding; Xencor: Consultancy, Research Funding. Daver:Abbvie: Consultancy, Research Funding; Celgene: Consultancy; Genentech: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; NOHLA: Research Funding; BMS: Consultancy, Research Funding; Immunogen: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Agios: Consultancy; Servier: Research Funding; Otsuka: Consultancy; Astellas: Consultancy; Forty-Seven: Consultancy; Daiichi Sankyo: Consultancy, Research Funding; Hanmi Pharm Co., Ltd.: Research Funding; Jazz: Consultancy; Sunesis: Consultancy, Research Funding; Glycomimetics: Research Funding. DiNardo:medimmune: Honoraria; abbvie: Consultancy, Honoraria; syros: Honoraria; daiichi sankyo: Honoraria; jazz: Honoraria; notable labs: Membership on an entity's Board of Directors or advisory committees; celgene: Consultancy, Honoraria; agios: Consultancy, Honoraria. Konopleva:Agios: Research Funding; Calithera: Research Funding; Stemline Therapeutics: Consultancy, Honoraria, Research Funding; Forty-Seven: Consultancy, Honoraria; Eli Lilly: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Cellectis: Research Funding; Amgen: Consultancy, Honoraria; F. Hoffman La-Roche: Consultancy, Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Ascentage: Research Funding; Kisoji: Consultancy, Honoraria; Reata Pharmaceuticals: Equity Ownership, Patents & Royalties; Ablynx: Research Funding; Astra Zeneca: Research Funding. Pemmaraju:mustangbio: Consultancy, Research Funding; abbvie: Consultancy, Honoraria, Research Funding; samus: Research Funding; celgene: Consultancy, Honoraria; cellectis: Research Funding; Stemline Therapeutics: Consultancy, Honoraria, Research Funding; novartis: Consultancy, Research Funding; plexxikon: Research Funding; Daiichi-Sankyo: Research Funding; sagerstrong: Research Funding; affymetrix: Research Funding; incyte: Consultancy, Research Funding. Wierda:Juno Therapeutics: Research Funding; Acerta Pharma Inc: Research Funding; Gilead Sciences: Research Funding; Pharmacyclics LLC: Research Funding; Genentech: Research Funding; AbbVie: Research Funding; GSK/Novartis: Research Funding; Oncternal Therapeutics Inc.: Research Funding; Cyclcel: Research Funding; Loxo Oncology Inc.: Research Funding; Janssen: Research Funding; Xencor: Research Funding; KITE pharma: Research Funding; Sunesis: Research Funding; Miragen: Research Funding. Garcia-Manero:Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding; Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding. Sasaki:Otsuka: Honoraria; Pfizer: Consultancy. Cortes:Jazz Pharmaceuticals: Consultancy, Research Funding; Sun Pharma: Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Research Funding; BiolineRx: Consultancy; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding. Khoury:Stemline Therapeutics: Research Funding; Angle: Research Funding; Kiromic: Research Funding. Jain:ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Pharmacyclics, an AbbVie company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Janssen Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Precision Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. O'Brien:Pfizer: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Acerta: Research Funding; Alexion: Consultancy; Amgen: Consultancy; Aptose Biosciences, Inc: Consultancy; Astellas: Consultancy; Celgene: Consultancy; Eisai: Consultancy; Gilead: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Kite: Research Funding; Janssen: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Regeneron: Research Funding; Sunesis: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Vaniam Group LLC: Consultancy; Verastem: Consultancy. Jabbour:Cyclacel LTD: Research Funding; Amgen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. OffLabel Disclosure: The use of ponatinib as frontline therapy for patients with Ph+ ALL.

Background: Inotuzumab ozogamicin (INO) and blinatumomab both improve survival in relapsed or refractory acute lymphoblastic leukemia (ALL) compared to conventional chemotherapy. The combination of INO with reduced-intensity mini-hyper-CVD chemotherapy in older adults with newly diagnosed ALL is safe and highly effective (Kantarjian H et al, Lancet Oncol 2018;19(2):240-8). The addition of blinatumomab to this regimen may further improve outcomes. Methods: Patients (pts) ≥60 years of age with newly diagnosed Philadelphia chromosome (Ph)-negative pre-B-cell ALL were eligible. Pts were required to have a performance status of ≤3, total bilirubin ≤1.5 mg/dl, AST/ALT ≤3x ULN and creatinine ≤2 mg/dl. Pts received mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 x 4 doses) for up to 8 cycles. INO was given at a dose of 1.3-1.8mg/m2 on day 3 of cycle 1 and 0.8-1.3mg/m2 on day 3 of cycles 2-4. Rituximab (if CD20+) and prophylactic IT chemotherapy were given for the first 4 cycles. Responding pts received POMP maintenance for up to 3 years. In order to decrease the risk of veno-occlusive disease (VOD), the protocol was amended in 3/2017 (pts 50+) to give INO in fractionated doses each cycle (0.6 mg/m2 on day 2 and 0.3 mg/m2 on day 8 of cycle 1; 0.3 mg/m2 on day 2 and 8 of cycles 2-4) and to administer 4 cycles of blinatumomab following 4 cycles of hyper-CVD plus INO, followed by maintenance with 12 cycles of POMP and 4 cycles of blinatumomab (1 cycle of blinatumomab after every 3 cycles of POMP). Results: 64 pts have been treated, 5 of whom were in complete remission (CR) at enrollment. Pt characteristics are summarized in Table 1. Median age was 68 years (range, 60-81 years); 27 pts (42%) were ≥70 years. 28% were positive for TP53 mutation, 19% were CRLF2 positive, and 27% had adverse-risk karyotype. 33/58 pts (57%) were CD20+ and received rituximab. Among 59 pts evaluable for morphologic response, 58 (98%) responded (CR, n=51; CRp, n=6; CRi, n=1). MRD negativity by 6-color flow cytometry was achieved in 48/62 pts (77%) after 1 cycle and 59/63 pts (94%) overall. There were no early deaths, and the 30-day and 60-day mortality rates were 0% and 3%, respectively. Among 63 pts who achieved remission, 9 (14%) relapsed, 3 (5%) underwent allogeneic SCT in first remission, 30 (48%) remain on treatment or have completed maintenance, and 21 (33%) died in CR/CRp. The rate of death in CR/CRp was higher in pts ≥70 years of age vs. 60-69 years (50% vs. 22%; P=0.02). Causes of death for pts in CR/CRp included: sepsis (n=7; all in pts 70 years and older), VOD (n=3), gunshot wound (n=1), dementia and deconditioning (n=1), end stage renal disease (n=1), MDS/AML (n=4; 3 in pts 70 years and older) and unknown causes (n=4). 6 pts (9%) developed VOD, 1 after subsequent allogeneic SCT. The rate of VOD was 6/64 (9%) with no difference in VOD in pts who did or did not receive blinatumomab. With a median follow-up of 37 months (range, 2-85 months), 34 pts (53%) were alive, 30 of whom (47%) were in CR and MRD negative status. The 3-year continuous remission and OS rates were 76% and 54%, respectively (Figure 1A). The 3-year continuous remission rate was 69% and 87% for pts age 60-69 and ≥70 years, respectively (P=0.25), and the 3-year OS rate was 63% and 42%, respectively (P=0.13; Figure 1B). The trend for worse survival in the pts ≥70 years was driven predominantly by the increased rate of death in CR/CRp in this older group. The outcomes of pts who did or did not receive blinatumomab were similar. Compared to a similar historical cohort of older pts treated with hyper-CVAD ± rituximab (n=77), mini-hyper-CVD + INO ± blinatumomab resulted in significantly higher 3-year OS (54% vs 32%; P=0.007). Conclusion: Reduced-intensity chemotherapy with hyper-CVD plus INO, with or without blinatumomab, is safe and effective in older adults with newly diagnosed Ph-negative ALL, with an overall response rate of 98% and 3-year OS rate of 54%. Further optimization of this regimen with less chemotherapy in patients 70 years and older is warranted to further decrease the rate of death in remission. Disclosures Short: Takeda Oncology: Consultancy, Research Funding; AstraZeneca: Consultancy; Amgen: Honoraria. Kantarjian:Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Research Funding; Cyclacel: Research Funding; Pfizer: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Immunogen: Research Funding; Amgen: Honoraria, Research Funding; Novartis: Research Funding; Takeda: Honoraria; Ariad: Research Funding; Agios: Honoraria, Research Funding; Astex: Research Funding; BMS: Research Funding; Daiichi-Sankyo: Research Funding. Ravandi:Xencor: Consultancy, Research Funding; Menarini Ricerche: Research Funding; Selvita: Research Funding; Cyclacel LTD: Research Funding; Macrogenix: Consultancy, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Jain:Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Precision Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, an AbbVie company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Sasaki:Otsuka: Honoraria; Pfizer: Consultancy. Daver:Otsuka: Consultancy; Astellas: Consultancy; NOHLA: Research Funding; Jazz: Consultancy; Forty-Seven: Consultancy; Agios: Consultancy; Immunogen: Consultancy, Research Funding; Celgene: Consultancy; Genentech: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Servier: Research Funding; Pfizer: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Hanmi Pharm Co., Ltd.: Research Funding; Glycomimetics: Research Funding; BMS: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding. Pemmaraju:sagerstrong: Research Funding; affymetrix: Research Funding; mustangbio: Consultancy, Research Funding; abbvie: Consultancy, Honoraria, Research Funding; samus: Research Funding; celgene: Consultancy, Honoraria; Daiichi-Sankyo: Research Funding; plexxikon: Research Funding; novartis: Consultancy, Research Funding; Stemline Therapeutics: Consultancy, Honoraria, Research Funding; cellectis: Research Funding; incyte: Consultancy, Research Funding. Khoury:Stemline Therapeutics: Research Funding; Angle: Research Funding; Kiromic: Research Funding. Alvarado:Jazz Pharmaceuticals: Research Funding; Abbott: Honoraria. Konopleva:Ablynx: Research Funding; Calithera: Research Funding; Stemline Therapeutics: Consultancy, Honoraria, Research Funding; Forty-Seven: Consultancy, Honoraria; Eli Lilly: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Cellectis: Research Funding; Amgen: Consultancy, Honoraria; F. Hoffman La-Roche: Consultancy, Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Ascentage: Research Funding; Kisoji: Consultancy, Honoraria; Reata Pharmaceuticals: Equity Ownership, Patents & Royalties; Astra Zeneca: Research Funding; Agios: Research Funding. Garcia-Manero:Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding. Kadia:Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Bioline RX: Research Funding; BMS: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Research Funding. Borthakur:Merck: Research Funding; Polaris: Research Funding; BioLine Rx: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tetralogic Pharmaceuticals: Research Funding; Cantargia AB: Research Funding; Eisai: Research Funding; Oncoceutics, Inc.: Research Funding; AbbVie: Research Funding; Agensys: Research Funding; Oncoceutics: Research Funding; NKarta: Consultancy; Bayer Healthcare AG: Research Funding; BMS: Research Funding; AstraZeneca: Research Funding; Cyclacel: Research Funding; Strategia Therapeutics: Research Funding; Incyte: Research Funding; Eli Lilly and Co.: Research Funding; Janssen: Research Funding; Novartis: Research Funding; Xbiotech USA: Research Funding; FTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Argenx: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Consultancy; Arvinas: Research Funding; BioTheryX: Membership on an entity's Board of Directors or advisory committees; GSK: Research Funding. Burger:BeiGene: Research Funding; Pharmacyclics, an AbbVie company: Research Funding; Gilead Sciences: Research Funding; Janssen Pharmaceuticals: Consultancy, Honoraria; Aptose Biosciences, Inc: Research Funding; AstraZeneca: Honoraria. Wierda:Genentech: Research Funding; Juno Therapeutics: Research Funding; KITE pharma: Research Funding; Sunesis: Research Funding; Miragen: Research Funding; Oncternal Therapeutics Inc.: Research Funding; Cyclcel: Research Funding; Loxo Oncology Inc.: Research Funding; Janssen: Research Funding; Xencor: Research Funding; GSK/Novartis: Research Funding; Pharmacyclics LLC: Research Funding; Acerta Pharma Inc: Research Funding; AbbVie: Research Funding; Gilead Sciences: Research Funding. DiNardo:syros: Honoraria; abbvie: Consultancy, Honoraria; daiichi sankyo: Honoraria; jazz: Honoraria; medimmune: Honoraria; notable labs: Membership on an entity's Board of Directors or advisory committees; celgene: Consultancy, Honoraria; agios: Consultancy, Honoraria. O'Brien:Astellas: Consultancy; Alexion: Consultancy; Gilead: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Celgene: Consultancy; Sunesis: Consultancy, Research Funding; Kite: Research Funding; Aptose Biosciences, Inc: Consultancy; Acerta: Research Funding; Verastem: Consultancy; GlaxoSmithKline: Consultancy; Eisai: Consultancy; Vaniam Group LLC: Consultancy; TG Therapeutics: Consultancy, Research Funding; Regeneron: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Amgen: Consultancy. Jabbour:AbbVie: Consultancy, Research Funding; Cyclacel LTD: Research Funding; Pfizer: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. OffLabel Disclosure: The use of inotuzumab ozogamicin and blinatumomab as frontline therapy for older patients with ALL

Coordinated multi-point (CoMP) joint transmission is considered as a key technique to mitigate inter-cell interference and improve the cell-edge performance in 3GPP LTE-Advanced. In this paper, a utility-based joint resource allocation approach is proposed to support CoMP joint transmission in orthogonal frequency division multiple access systems. Two different utility functions are considered with diverse quality of service provisioning. The objective is to maximize the sum utility of a clustered CoMP network, considering mixed real-time voice over IP (VoIP) and best-effort (BE) traffic patterns. A centralized joint resource allocation algorithm is proposed by decoupling the optimization problem into per-subchannel subproblems. Further more, a greedy user selection based low-complexity algorithm is proposed for practical implementation. For the sake of performance comparison, the proportional-fair based joint scheduling, as well as two non-coordinated scheduling schemes are also evaluated. Via system-level simulation we show that the proposed algorithms not only substantially improve the cell-edge spectrum efficiency of BE users, but also significantly decrease the packet drop ratio and call outage ratio of VoIP users.

A meta-analysis of the comparative distance education (DE) literature between 1985 and 2002 was conducted. In total, 232 studies containing 688 independent achievement, attitude, and retention outcomes were analyzed. Overall results indicated effect sizes of essentially zero on all three measures and wide variability. This suggests that many applications of DE outperform their classroom counterparts and that many perform more poorly. Dividing achievement outcomes into synchronous and asynchronous forms of DE produced a somewhat different impression. In general, mean achievement effect sizes for synchronous applications favored classroom instruction, while effect sizes for asynchronous applications favored DE. However, significant heterogeneity remained in each subset.