bluuebunny/crossref_metadata_2025_split huggingface dataset:
The delivery of value-based healthcare for children with osteosarcoma at Children’s Cancer Hospital Egypt.
Authors: Soliman Ranin , Eweida Wael , Zamzam Manal , Elhaddad Alaa , Abouelnaga Sherif 
Published: September 2018

e18310 Background: Aim of the study was to develop a system to measure the value of health care services delivered to osteosarcoma patients, through developing a standardized set of patient-centered outcomes for Osteosarcoma and using a consistent approach to measure the costs of Osteosarcoma care throughout all care cycles. Methods: The Porter’s Outcomes Measurement Hierarchy was used to define the domains of outcomes reporting for Osteosarcoma, which included three levels of measuring outcomes; health status achieved or retained, process of recovery, and sustainability of health. Time-driven activity-based costing (TDABC) approach was used a guide to determine the actual costs of healthcare services delivered to Osteosarcoma patients throughout their journey of cure. Results: Osteosarcoma outcome measurement tools and questionnaires were standardized based on the following domains: survival, degree of health or recovery, time to recovery and return to normal activities, disutility of care and treatment processes, sustainability of health and nature of recurrences, and the long-term consequences of therapy. The standardized outcome reporting tools under each domain included: toxicity reporting using NCI-Common Toxicity Criteria version 4.0, Pediatric Quality of Life Inventory (PedsQL) Cancer module, Musculoskeletal Tumour Society Score (MSTS) for functional outcome assessment, Palliative Care Outcomes Scale (POS). Process mapping was done for each step involved in the delivery of health care services to children with Osteosarcoma at Children’s Cancer hospital Egypt (57357 Hospital). Conclusions: Developing a standardized system for measuring the health outcomes of Osteosarcoma and the total costs for delivering the health care services is fundamental to measure and improve the value of health care delivered to Osteosarcoma patients.
Hospitalization for patients in the United States (US) and European Union (EU) treated with inotuzumab ozogamicin (InO) vs standard of care (SOC) for relapsed/refractory acute lymphoblastic leukemia (R/R ALL) in a global phase 3 trial.
Authors: Su Yun , van Oostrum Ilse , Vandendries Erik , Welch Verna , Loberiza Fausto Rodriguez 
Published: September 2018

e18500 Background: InO, an anti-CD22 antibody-calicheamicin conjugate, with its once a week, 1-hour infusion schedule, has demonstrated lower hospital utilization in association with superior clinical activity, favorable patient-reported outcomes (PROs), and a generally manageable safety profile versus SOC (intensive chemotherapy) for R/R ALL in the phase 3 INO-VATE trial. Here, regional-specific hospitalizations in the trial are presented. Methods: Patients receiving study treatment and recruited from the US and the EU were included in the analyses. The total number of days hospitalized for each patient was calculated. Hospital days prior to randomization and those after the end of study treatment were excluded. Due to different treatment durations for InO and SOC (median 1 vs 3 cycles), calculations were reported for cycle 1 treatment period (randomization to end of cycle 1) and for the entire treatment period (all cycles - randomization to end of treatment). Results: A total of 281 patients were available for the analyses. 154 were from the US and 127 from 11 of the EU countries. The median and mean hospitalization days were shorter for patients in the InO arm compared to the SOC arm across both regions (Table). The difference between the two treatment arms appear to be greater in the US compared to the EU. Hospitalizations in the US appear to be shorter than in the EU, particularly for patients receiving InO. Conclusions: InO treatment in R/R ALL is associated with less hospitalization across both the US and EU compared to SOC, consistent with InO’s better efficacy, tolerability, PRO and dosing schedule. The finding that US has lower hospitalization than the EU might be explained by different patient care practices in the two regions. Given that hospitalization is the biggest cost driver in cancer care, the discrepancy may lead to greater cost-savings in healthcare systems where hospitalizations are strictly managed. Clinical trial information: NCT01564784. [Table: see text]
Cytogenetic evolution between diagnosis and relapse and impact on acute myeloid leukemia (AML) reinduction outcomes.
Authors: Brunner Andrew Mark , Werner Lillian , Lombardi Story Jennifer , Hobbs Gabriela , Amrein Philip C. , Hasserjian Robert P , Neuberg Donna S. , Fathi Amir Tahmasb 
Published: September 2018

e18509 Background: Changes in the subclonal composition of AML may occur after diagnosis and be a mechanism of relapse. Cytogenetic changes between diagnosis and relapse may reveal evolution in clonal composition. We sought to determine whether evolution of patient cytogenetics impacts the response to salvage chemotherapy among AML patients who relapse after first remission. Methods: We identified adults with relapsed AML between 2001-2015. Studied patients received induction at diagnosis, achieved remission, relapsed, and received intensive salvage. APL and primary refractory AML were excluded. We identified cytogenetic abnormalities at relapse, and any clonal changes from diagnosis (gain/loss/no change). Associations with CR2 were analyzed by Fisher’s exact test. OS was from salvage therapy to death or censored at last known alive, with Kaplan Meier estimates. Results: 69 patients (median 54 yo, 58% male) received salvage therapy for relapsed AML. Most (81%) had de novoAML. Patients had favorable (7%), intermediate (70%), and adverse risk (23%) cytogenetics at diagnosis; 51% were normal karyotype. 94% received 7+3-based induction. 42% underwent allo-HCT in CR1. Salvage included 7+3 (n = 22), MEC (n = 36), HiDAC (n = 4), or other regimens (n = 7). Median time from CR1 to relapse was 10 mo (IQR 5, 18). At relapse, 29 patients (42%) gained cytogenetic abnormalities, 8 (12%) lost abnormalities, and 31 (45%) were unchanged. The most common acquired abnormalities involved chromosomes 7, 11, or 17 (each n = 6). 55% achieved CR2/CRi2 (CR2 w/ chromosome gain 48%, loss 38%, no change 65%). Longer CR1 duration was associated with greater likelihood of achieving CR2/CRi2 (p = 0.003). Accounting for CR1 duration, cytogenetic evolution from diagnosis to relapse was not significantly associated with CR2. Improved OS was seen with non-adverse diagnosis cytogenetics (p = 0.0003), longer CR1 (p = 0.035), and transplant in CR1 (p = 0.04). Conclusions: Although AML evolution frequently occurs between diagnosis and relapse (54% of this cohort had cytogenetic changes at relapse), this did not impact CR2 or overall survival. Rather, duration of CR1, likely a surrogate for depth of remission, significantly impacted outcomes.
Hospital readmission rate for febrile neutropenia (FN) following high dose cytarabine (HiDAC) consolidation chemotherapy for acute myeloid leukemia (AML).
Authors: Siebenaller Caitlin , Radivoyevitch Tomas , Cheng Connie , Carraway Hetty , Mukherjee Sudipto , Advani Anjali S. , Gerds Aaron Thomas , Nazha Aziz , Maciejewski Jaroslaw P. , Earl Marc A. , Waldron Madeline , Sekeres Mikkael A. 
Published: September 2018

e18513 Background: FN is an anticipated complication of consolidation with HiDAC for AML, though precise descriptions of incidence, type, and severity of infection leading to FN are lacking. Since AML patients (pts) with FN after HiDAC are routinely readmitted to the hospital, there is a likely impact on measures of quality and value in this population. Methods: Our primary aim was to define the rate of FN inpatient readmissions among all HiDAC cycles. Secondary aims included: estimating rates of all-cause readmissions, clinical (e.g., probable pneumonia per imaging) and microbiologically-documented infections, and identify pts-specific risk factors associated with readmission. Readmission per patient were modeled using Poisson regression, with means proportional to total cycles exposed, and logistic regression for the probability of FN per treatment cycle. Results: We identified 150 AML pts ≥ 18 years of age, who received at least one cycle of HiDAC consolidation (1000-3000 mg/m2 for six doses) in 2009-2016. The median age was 50 (range 19-69); 55% were female and 45% were male. For 417 HiDAC cycles analyzed (87% at 3000 mg/m2), all pts received flouroquinalone prophylaxis and the overall readmission rate was 49% (203/417), of which 86% (174/203) were for FN. Median time to FN hospital admission was 18 days (range 10-22) from the start of HiDAC. Of the 174 FN readmissions, 60% had documented infections. Of these infections, 35% were bacteremia, 29% other bacterial, 24% fungal, 6% sepsis, and 6% viral. Females had higher FN readmission rates (RR 1.7 (1.3, 2.4) p = 0.007), as did pts with higher BMI (RR 1.06 (1.01, 1.09) p = 0.005), while age and HiDAC dose were not associated with readmission. Only 34% of all readmissions were in the absence of a documented infection. Conclusions: The majority of FN readmissions were associated with clinical or microbiologically documented infections and are not avoidable. Females and pts with higher BMI were more likely to be readmitted. Readmission of AML pts following HiDAC is expected, and therefore, should be excluded from measures of value and quality.
Association of CDKN2A/2B deletion with homozygous deletion of TCR- γ gene in T-ALL.
Authors: Chopra Anita , Singh Jay , Verma Deepak , Rajput Nishi , Bakhshi Sameer , Singh Amar Ranjan , Kumar Rajive 
Published: September 2018

e18516 Background: T-lineage acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease that arises in a multistep fashion through acquisition of several genetic aberrations. Absence of biallelic deletion of TCR-γ (ABD), a marker of immaturity, and CDKN2A/2B deletion have been identified as poor predictors of outcome in T-ALL treated with contemporary protocols. The aim of this study was to determine the correlation between ABD and CDKN2A/2B in Indian T-ALL patients. Methods: A total of 31 cases of T-ALL, diagnosed on morphology, cytochemistry and immunophenotyping, were included in the study. The age of the patients ranged from 1-50 years. The patients were investigated for CDKN2A/2B deletion by multiplex ligation dependent probe amplification (MLPA) using the commercially available probe set P383 (MRC Holland). The status of the deletion of TCR- γ was determined using quantitative assay described by Gutierrez et al.1 Results: Absence of biallelic deletion of TCR- γ gene were found in 14 (45.16%) patients. Homozygous deletion was seen in 13 (41.93%) patients while monoallelic deletion was seen in 5 (16.12%) patients. CDKN2A/2B deletions were found in (48.38%) patients. On correlation of CDKN2A/2B deletion and TCR- γ deletion, it was found that CDKN2A/2B deletion was found in 2/14 (14.28%) patients with ABD and 10/13 (76.92%) patients with homozygous deletion. Conclusions: CDKN2A/2B deletion are more common in patients with homozygous deletion of TCR- γ gene.
Treatment of adolescents and young adults with Philadelphia negative acute lymphoblastic leukemia (AYA Ph-ALL) using a risk and response based protocol with extended intensification and high dose methotrexate: A report from a single center in Saudi Arabia.
Authors: Eldadah Saleem , Jastaniah Wasil , Alsaeed Ahmad , Abrar Mohammed Burhan , Abdelaal Mohamed A. , Alzahrani Zayed , Rajkhan Walaa , Warsi Ashraf , Alsobhi Enaam , Alahmadi Majed , Ibrahim Amro , Higazi Ahmad , Ahmed Ayoub , El-Hemaidi Ihab , Absi Ahmed A. 
Published: September 2018

e18527 Background: Studies have shown superior outcomes of AYA Ph-ALL when treated with pediatric or pediatric-inspired protocol. Since 2003 we used a modified Children’s Oncology Group (COG) protocol to treat AYA Ph-ALL aiming to improve outcomes. Methods: This study involved 67 consecutive patients aged 14-35 years with Ph-ALL diagnosed between October 2003 and March 2016. Patients with precursor B ALL, CNS1/CNS2, and negative day 29 minimal residual disease (MRD-) received single interim maintenance (IM) and delayed intensification (DI) (Arm B). While CNS3 or MRD+ patients received double IM and DI (Arm C). Patients with T cell ALL received double IM with high dose methotrexate (HDMTX) in IM#1, and double DI (Arm C+HDMTX). Dexamethasone was used in all patients but prophylactic cranial irradiation was not utilized. Results: Median age at diagnosis was 17 years with 24 (35.8%) 18 years and older. CR rate, induction death, relapse rate, 4 year event free survival (EFS) and overall survival (OS) were 93.7%, 4.5%, 19.4%, 71.4%±6.0 and 81.8%±5.0; respectively. Of the 57 patients with available MRD, 44 (77.2%) were MRD-. Day 29 MRD status significantly impacted the outcomes (EFS: 78.6%±6.8 vs. 49.2%±15.4; p = 0.007 and OS: 90.5%±4.5 vs. 49.4%±22.0; p = 0.04) for MRD- vs. MRD+ patients; respectively). Outcomes were not different for T (n = 21) vs. B (n = 46) phenotypes (EFS: 69.2%±7.6 vs. 75.6%±9.5; p = 0.57 and OS: 79.8%±6.5 vs. 85.7%±7.6; p = 0.98; respectively). Grade 3 and above toxicities were venous thromboembolism (VTE) in 9 (13.4 %), avascular necrosis (AVN) in 9 (13.4 %) and pancreatitis in 3 (4.5 %) patients. Four patients (6%) died in CR and 2 died with secondary AML. Conclusions: Improved outcomes were observed with OS rate exceeding 90% for MRD negative patients. Therapy was tolerated relatively well, however, AVN and VTE occurred frequently. This suggests that utilizing a modified COG backbone in AYA Ph-ALL patients up to 35 years of age is feasible, however, further modification is warranted to reduce toxicity and improve outcomes in MRD positive patients.
Burden of illness in patients with acute myeloid leukemia aged ò65 years ineligible for intensive chemotherapy.
Authors: Lafeuille Marie-Helene , Sundaram Murali , Lefebvre Patrick , Emond Bruno , Romdhani Hela , Senbetta Mekre 
Published: September 2018

e18529 Background: Management of older patients with acute myeloid leukemia (AML) is challenging due to a higher comorbidity burden, poorer performance status and less favorable biology. This study assessed treatment patterns and healthcare resource utilization (HRU) in the US in patients diagnosed with AML aged ≥65 years who did not receive intensive chemotherapy. Methods: Patients aged ≥65 years with ≥2 diagnoses for AML were identified from the Truven Health MarketScan Analytics Databases (01/01/2011-07/31/2016). Patients had ≥1 bone marrow diagnosis procedure (BX; first AML diagnosis following BX defined as the index date), ≥12 months of continuous eligibility pre-index, no treatment with intensive chemotherapy at any time, no diagnosis for AML relapse or remission or stem cell transplant before BX, and <2 diagnoses for other blood cancers pre-index. Post-index treatment patterns and HRU were reported. Results: 1,492 patients with AML were identified (mean [standard deviation] age: 76.8 [7.0] years; 61% males). Mean post-index follow-up was 212 (255) days and 43% were treated with antineoplastic agents (AA). Most common first-line treatments were azacitidine (35%), decitabine (32%) and hydroxyurea (16%). 4% received low-dose cytarabine. Patients with ≥1 blood transfusion (61%) received 8.9 (9.5) transfusions per month during 177 (244) days on average. A total of 3% received stem cell transplant. Patients had a mean of 3.7 (5.3; pre-index: 0.4 [0.7]) days of hospitalization, 0.2 (1.4; pre-index: 0.0 [0.2]) days of hospice care, and 5.2 (4.5; pre-index: 2.6 [2.4]) office visits per month post-index. Compared to treated patients, untreated patients (32%; i.e., patients with no AA, blood transfusion or stem cell transplant) had fewer days of post-index follow-up (106 vs. 263), more days of hospitalization (4.8 vs. 3.2), and of hospice care (0.4 vs. 0.1), and fewer office visits (3.8 vs. 5.8) per month (all P<0.01). Conclusions: Patients ≥65 years diagnosed with AML not receiving intensive chemotherapy incurred more HRU after AML diagnosis. About a third was untreated and had higher HRU than treated patients. This suggests major unmet needs for well-tolerated treatment options for these patients.
Volumetric modulated arc therapy versus conformal radiation therapy for conditioning of allogenic bone marrow transplantation (ABMT) in acute lymphoblastic leukemia.
Authors: Chilaca Rosas María Fátima , Gutierrez Marquez Jesus Gerardo , López Valencia Alberto , Urueta Cuellar Héctor , Hernández García Juan Carlos , Gutierrez Juan Carlos Heredia , Olmos Guzmán Alejandro , Adame Gonzalez Christian Salvador , Campos Gomez Saul , Motola Daniel , González Noguez Alicia Guillermina , Rodrìguez Cortes Jeanette , Montaño García Carla , Rosales Gamboa Marco Aurelio , Aguilar Jose Luis 
Published: September 2018

e18532 Background: Total body irradiation is performed as part of the conditioning regimen for patients eligible for ABMT. New techniques have been investigated to target more selectively of total medular irradiation. Purpose:In this study a preclinical investigation was undertaken to explore a treatment technique for total marrow irradiation using a volumetric modulated arc technique (VMAT) versus conformal radiation therapy. Methods: Ten patients conditioning for ABMT between the periods of April to October 2016 were evaluated. A comparative dosimetric analysis between conformal and VMAT radiation therapy techniques was performed. Treatment plan was performed by using ten arcs with three isocenters with a collimator angle between 10°-100°, optimized for energy of 6MV. The prescribed dose was 12 Gy. In order to cover the bone marrow the PTV was defined as the bones from the cranium vertex to the middle third of the femur. The organs at risk constraints had a median restriction of ≤ 10Gy. Radiation therapy integral dose, conformity, homogeneity and coverage index were evaluated. Results: The average volume of body irradiated was 52,433cc (37,221-73,968cc), the average volume of the PTV was 10,379cc (8,449-13,325cc). The average dose for the planning target volume (PTV) using conformal radiation technique and with VMAT was 15.3Gy and 13.1 Gy (p < 0.0001), respectively. The median dose for the organs at risk with the conformal technique was 17.5Gy and 10.4Gy for the VMAT (p = 0.0013). The median of index of conformity using the conformal technique was 5.21 and 1.99 with VMAT (p = 0.0003). The homogeneity index was 1.87 and 1.37(p < 0.0001) respectively. The quality of coverage was 0.82 and 0.81 (p = 0.951), respectively. The integral dose was 7,699.73 and 6,615.8 kg/Gy (p < 0.0001) respectively. Conclusions: For patients conditioning for ABMT requiring bone marrow irradiation the intensity modulated VMAT radiation therapy technique offers a better conformity and homogeneity index and also offers a reduction in the integral dose, suggesting the possibility of incorporating this technique in the treatment options for patients.
Impact of the type of first-cancer therapy in therapy-related myelodysplastic syndromes outcomes.
Authors: Alfonso Pierola Ana , Montalban-Bravo Guillermo , Takahashi Koichi , Jabbour Elias , Kadia Tapan M. , Ravandi Farhad , Cortes Jorge E. , Dinardo Courtney Denton , Daver Naval Guastad , Borthakur Gautam , Pemmaraju Naveen , Konopleva Marina , Bueso-Ramos Carlos E. , Pierce Sherry , Kantarjian Hagop M. , Garcia-Manero Guillermo 
Published: September 2018

e18555 Background: Therapy-related myelodysplastic syndromes (t-MDS) are known to have poor outcomes. The impact of the therapy received for the first cancer remains unknown. Methods: 228 t-MDS diagnosed between July 2001 and December 2015 were retrospectively reviewed. Results: Median age at diagnosis of t-MDS was 66 years (range 13-87). Previous malignancies: 54% hematological cancers and 47% solid tumors. 14% had multiple cancers before the t-MDS. Previous therapy received: 119 (52%) chemotherapy (CT), 17 (8%) radiotherapy (RT), or 92 (40%) both (Table). Median time to develop t-MDS was 73 months (range 5-355). According to IPSS, 13 patients (6%) had low-risk, 65 (29%) intermediate-1 risk, 119 (53%) intermediate-2 risk and 29 (13%) high-risk. 124 patients (58%) had complex karyotype. The most frequent cytogenetic abnormalities detected were: -7/7q (n=99; 46%), -5/5q (n=77; 36%), and +8 (n=13; 6%). TP53was observed in 51% (n=21/41). Median OS was 12 months (CI95% = 10-14). Univariate and multivariate analysis revealed that CT vs RT (p=0.028; HR [CI95%] = 1.988 [1.08-3.67]), and higher IPSS risk (low: p=0.027; intermediate-1: p=0.285 HR [CI95%] = 1.48 [0.72-3.01]; intermediate-2: p=0.055, HR [CI95%] = 1.95 [0.99-3.88]; high: p=0.015 HR [CI95%] = 2.59 [1.21-5.55]), had a poor impact in OS. No statistical differences between OS and type of CT received, molecular or cytogenetic alterations were observed. However, complex karyotype (71% vs 51%, p=0.007) and -7/7 abnormalities (61% vs 36%; p=0.001) were more frequent in patients who had received platinum; -7/7q- abnormalities were also associated to alkylating agents (50% vs 27%, p=0.012), antibiotics (74% vs 42%; p=0.003) and topoisomerase inhibitors (60% vs 37%; p=0.002). Conclusions: t-MDS is associated with poor outcomes. Receiving CT vs RT and higher IPSS risk had a poor impact in OS. The type of CT may be associated with specific cytogenetic alterations. [Table: see text]
Phase I trial study of bendamustine, ofatumumab, and pentostatin (BOP) as salvage regimen for patients with relapsed or refractory non-Hodgkin’s lymphoma or chronic lymphocytic leukemia.
Authors: Thomas Colin , Gaballa Sameh , DiMeglio Martina , Alpdogan Seyfettin Onder , Carabasi Matthew H. , Chapman Andrew E. , Flomenberg Neal , Wagner John L. , Filicko Joanne , Weiss Mark Adam 
Published: September 2018

e19005 Background: No standard salvage regimen exists for patients (pts) with relapsed or refractory (RR) NHL or CLL. Bendamustine, pentostatin and ofatumumab have activity in pts with CLL and NHL, but have not been combined as a single regimen. We conducted a phase I trial to assess the safety of this regimen. Methods: Pts with RR B-NHL or CLL were eligible. The design was a standard 3+3 using escalating doses of Bendamustine (50, 70, or 90 mg/m2 D1-2), Pentostatin (4 mg/m2 D1), and Ofatumumab (cycle 1: 300 mg D1; cycle 2-6: 1000 mg D2) every 28 days. Responses were assessed after cycle 3. Results: Ten pts were enrolled (6M/4F). Median age was 56 (range 37-65). Pts had follicular (FL) NHL (n = 2), CLL or SLL (n = 6), primary mediastinal B-cell lymphoma (PMBL) (n = 1), and extra-nodal marginal zone (MZL) NHL (n = 1). Pts had relapsed (n = 7) or refractory disease (n = 3) and received a median of 3 prior lines of therapy (range 1-4). Two CLL pts had high risk cytogenetics: 11p (n = 1) and 17p (n = 1). Most NHL pts (3/4) had stage 4 disease and all were refractory to rituximab. The ORR was 90% (PR = 5 pts: FL = 2, CLL/SLL = 3; CR = 4; CLL = 3, MZL = 1). One pt with PMBL progressed on treatment and died. One pt with CLL relapsed after 6 months. After a median follow up of 17 mo, the OS was 90% and PFS was 80%. Two pts (FL and CLL/SLL) subsequently underwent allogeneic stem cell transplant. DLT was not reached. Grade 3-4 toxicities included electrolyte imbalance (50%), neutropenia (30%), thrombocytopenia (30%), tumor lysis (20%), neutropenic fever (20%), and infusion reactions (10%). Common grade 1-2 toxicities were hyperglycemia (90%), thrombocytopenia (80%), nausea (80%), edema (80%), fatigue (80%) and neutropenia (70%). Conclusions: The BOP regimen is well tolerated and safe in pts with RR B-NHL or CLL. No DLT toxicity was reached at the highest bendamustine dose of 90mg/m2. Targeted therapies have largely supplanted the role of chemo-immunotherapy in the salvage setting. This trial was initiated in the pre-ibrutinib era and accrual to the planned phase II portion is on hold as pts now receive targeted therapy as salvage therapy. BOP might be an option for pts refractory to other strategies. Clinical trial information: NCT01352312.