tbuckley/cabot-search huggingface dataset:
Real-World Data Indicates That the Addition of Etoposide to Idarubicin and Cytarabine (3+7) Induction in Young Adults (&lt;60 years) with AML Does Not Improve Survival or Remission Rates
Authors: Syed Osman Ahmed, Fahad Almohareb, Mahmoud Aljurf, Modhi Alhussinan, Dalal Bawazeer, Hazza A Alzahrani, Fahad Z. Alsharif, Said Y Mohamad, Amr Hanbali, Feras Alfraih, Marwan Shaheen, Riad O. El Fakih, Shahrukh Hashmi, Muhamad Hitham Almahayni, Ali Al Ahmari, Shad Ahmed, Wahiba Chebbo, Ahmad Salih Alotaibi, Abdul Mannan, Ghada el Gohary, Osama Ali, Maamoun Alsermani, Farhan Anjum, Ghada Aljuhani, Fazal Hussain, Naeem A. Chaudhri, Walid Rasheed
Journal: Blood (2016)
Preoperative imaging for staging of cutaneous melanoma in the United States: A population-based analysis.
Authors: Dana Haddad, David Etzioni, Barbara A. Pockaj, Richard J. Gray, Nabil Wasif
Journal: Journal of Clinical Oncology (2013)

9034 Background: Routine imaging for staging of early stage cutaneous melanoma is not recommended by National Comprehensive Cancer Network (NCCN) guidelines. Besides the low probability of finding metastatic disease, detrimental aspects include false-positives and additive cost. We sought to investigate the use of imaging for staging of cutaneous melanoma in the United States. Methods: Patients with newly diagnosed clinically node negative cutaneous melanoma between 2000-2007 were identified from the Surveillance Epidemiology End Results-Medicare registry. Any imaging performed within 90 days following diagnosis was considered a staging study. Patients with metastatic disease were excluded. Results: A total of 25,643 patients were identified, of whom 10,775 (42%) underwent imaging. The mean age was 76.1 years, with the majority being male (61.8%) and Caucasian (98.4%). Breakdown by T classification of the primary was as follows: T1 (63%), T2 (17%), T3 (12%), and T4 (8%). A chest Xray was performed for 9,737 (38.0%), while 3,176 (12.4%) underwent advanced staging imaging studies; PET (7.2%), CT (5.9%), MRI (0.6%), and Ultrasound (0.4%). The use of advanced imaging steadily increased over the period of our study from 9.0% in 2000 to 16.3% in 2007 (p&lt;0.001). When stratified by T classification, advanced imaging was used for 8.9% of T1, 14.5% of T2, 18.8% of T3 and 27.0% of T4 tumors (p&lt;0.001). Similarly, node positive patients (4.7%) underwent advanced imaging 33.4% of the time compared to 11.3% for node negative patients (p&lt;0.001). On multivariate analysis, factors predictive of advanced imaging include higher T classification (OR 3.12 T4 vs. T1, CI 2.77-3.52, p&lt;0.001), node positivity (OR 2.70, CI 2.36-3.09, p&lt;0.001), more recent year of diagnosis (OR 2.01 2007 vs. 2000, CI 1.71-2.37, p=0.006), high school education (OR 1.62, CI 1.43-1.83, p&lt;0.001), non-Caucasian race (OR 1.37, CI 1.05-1.77, p=0.018), and male gender (OR 1.12, CI 1.03-1.21, p=0.006). Conclusions: Contrary to current recommendations, performance of advanced imaging for staging of early stage cutaneous melanoma is increasing in the Medicare population. Further research is needed to identify factors driving this increase.
PERFORMANCE OF THE MAGGIC HEART FAILURE RISK SCORE IN JAPANESE ACUTE HEART FAILURE PATIENTS: A REPORT FROM THE WEST TOKYO HEART FAILURE REGISTRY
Authors: Mitsuaki Sawano, Taku Inohara, Yasuyuki Shiraishi, Shun Kohsaka, Takashi Kohno, Ayumi Goda, Atsushi Mizuno, Yasumori Sujino, Yuji Nagatomo, Keitaro Mahara, Keiichi Fukuda, Tsutomu Yoshikawa
Journal: Journal of the American College of Cardiology (2017)
Abstract 175: Doxorubicin and Acute Exercise Training Impair Diastolic Before Systolic Function in a Murine Model of Cancer
Authors: Joseph R Libonati, Kathleen Sturgeon, Keri Schadler, Geetha Muthukumaran, Dennis Ding, Akinyemi Bajulaiye, Nicholas Thomas, Victor A Ferrari, Sandra Ryeom
Journal: Circulation Research (2013)

Introduction: Cardiotoxicity often occurs in cancer patients treated with doxorubicin (DOX). DOX induces cardiomyocyte death, due in part to DOX-mediated DNA damage, myofiber degeneration, ischemia-related metabolic alterations, and activation of apoptotic pathways. While exercise is often recommended for cancer patients, it remains unclear whether the metabolic stress of exercise with DOX treatment benefits or impairs cardiac performance. Purpose: To test the hypothesis that acute exercise training performed with DOX therapy offsets cardiotoxicity. Methods: B16F10 melanoma cells (3x10 5 ) were injected into 6-8 week old male C57BL/6 mice (n= 48). A 4 mg/kg cumulative dose of DOX (IP) was administered over 2 weeks and exercise (EX) consisted of treadmill walking (45 min/d, 10 m/min, 5 days/week, 2 weeks). Four groups were tested: 1) Sedentary (SED) +Vehicle, 2) SED +DOX, 3) EX+Vehicle, 4) EX+DOX. Echocardiography [LV systolic (EF, %) and diastolic (E/A ratio) function] and tissue harvest were performed 48 hours after EX. Results: Tumor volume was attenuated in DOX and lowest in EX+DOX (p&lt;0.05). Body weight (BW), heart weight (HT), HT/BW, and HT/Tibia were attenuated in DOX (p&lt;0.05) and were lowest in EX+DOX. LV fibrosis increased with DOX (p&lt;0.05) and was greatest in EX+DOX (SED+Vehicle 2 ± 0.3%, SED+DOX 4 ± 0.5%, EX+Vehicle 3 ± 0.3%, and EX+DOX 6 ± 0.4%; p&lt;0.05). Cardiomyocyte area and β myosin heavy chain gene expression were similar between groups. Diastolic function was reduced with DOX and EX+DOX (both p&lt;0.05), but systolic function was similar between groups. DOX induced significant alterations the expression profiles of genes in the mTOR signaling pathway, with similar expression patterns in SED+DOX and EX+DOX. Insulin improved in vitro cardiomyocyte cell survival (p&lt;0.05) to a greater extent than IGF-1 treatment during DOX. Neither insulin nor IGF-1 impacted cardiomyocyte proliferation during DOX. Conclusion: While the addition of EX to DOX treatment more effectively inhibited tumor growth, EX did not alleviate DOX mediated LV diastolic impairment, and actually increased LV fibrosis. Acute, short term exercise appears to impair LV function in DOX-treated mice. Exercise-induced reductions in insulin secretion may underlie this effect.
Clinical Features and Prognostic Assessment of Nodal Marginal Zone B-Cell Lymphoma, a Rare Disease with Follicular-Like Behaviour.
Authors: Luca Arcaini, Marco Paulli, Sara Burcheri, Emanuela Boveri, Andrea Rossi, Michele Spina, Francesco Passamonti, Mauro Montanari, Andrea Gallamini, Lilj Uziel, Monica Crugnola, Francesca Montanari, Cristiana Pascutto, Enrica Morra, Mario Lazzarino
Journal: Blood (2006)
TWELVE MONTH FOLLOW-UP DATA FROM THE ONYX CORE TRIAL: ANGIOGRAPHIC AND CLINICAL PERFORMANCE OF NEXT GENERATION RESOLUTE ONYX DRUG-ELUTING STENT
Authors: Matthew J. Price, Richard Shlofmitz, Douglas Spriggs, Thomas Haldis, Paul Myers, Alexandra Popma-Almonacid, Akiko Maehara, Beth Moe, Yun Peng, Roxana Mehran
Journal: Journal of the American College of Cardiology (2017)
Pemetrexed in patients (pts) with relapsed small cell lung cancer (SCLC): A phase II study from the Hoosier Oncology Group
Authors: N. H. Hanna, R. Ansari, S. Bhatia, R. Govindan, D. Bruetman, M. Hosford, W. Fisher, A. White, T. Breen, B. Juliar
Journal: Journal of Clinical Oncology (2006)

7063 Background: Patients with relapsed SCLC have a dismal prognosis. Pemetrexed is a well tolerated agent, which is active against non-small cell lung cancer. We postulated that Pemetrexed may also be active and well tolerated in pts with relapsed SCLC, for whom few effective options exist. Methods: Eligible pts had small cell or a poorly differentiated neuroendocrine cancer, received 1 or 2 prior chemotherapy regimens and had an ECOG PS 0–2. Pts received Pemetrexed 500 mg/m 2 iv once every 3 weeks along with vitamin B 12 , folic acid, and dexamethasone for up to 6 cycles or progressive disease or intolerable side effects. Chemosensitive (S) pts (relapse &gt; 90 days following 1st line chemo) and chemoresistant (R) pts (PD ≤ 90 days following 1st line chemo) were analyzed separately. The primary objective of this phase II study was to estimate the clinical benefit rate [partial response (PR) or stable disease (SD)] in the 2 populations. Pts were to be accrued in 2 stages. If 8 of 18 and 3 of 21 pts achieved a PR or SD in the S and R populations, respectively, accrual would have continued to a total of 46 (S arm) and 50 (R arm) pts in each arm. Results: From 1/05 to 9/05, 43 pts were enrolled. Criteria to proceed to stage II were not met for either arm. S arm (n = 20): M/F 12/8; median age 63 (range, 45–79), PS 0/1/2 7/8/5. R arm (n = 23): M/F 17/6; median age 65 (range, 42–79), PS 0/1/2 7/10/6. Select grade 3/4 toxicities (combined group): 4 pts with neutropenia; 2 pts each with anemia, AST/ALT, bilirubin elevation; 1 pt each with thrombocytopenia, febrile neutropenia, infection with neutropenia, and rash. S arm: 1 PR and 1 SD were confirmed. R arm: 1 PR and 1 SD were confirmed. Conclusions: Pemetrexed 500 mg/m 2 has minimal single agent activity in pts with relapsed SCLC. [Table: see text]
Early Treatment Intensification in High Risk (HR)-AML Patients Using Allogeneic Hematopoietic Stem Cell Transplantion in a Randomized Multicenter Setting.
Authors: Thomas Illmer, Markus A. Schaich, Christian Thiede, Uwe Platzbecker, Wandt Hannes, Ho D. Anthony, Thiel Eckhard, Schmitz Norbert, Einsele Hermann, Neubauer Andreas, Andresen Reinhard, Aulitzky Walter, Haehnel Matthias, Serve Hubert, Berdel Wolfgang, Bornhaeuser Martin, Ehninger Gerhard
Journal: Blood (2007)
QRS FRAGMENTATION PREDICTS MYOCARDIAL FIBROSIS, LEFT VENTRICULAR DYSFUNCTION AND VENTRICULAR TACHYCARDIA IN CHAGAS’ DISEASE
Authors: Edgar Alexander Illescas González, Gabriela Melendez-Ramirez, Diego Araiza-Garaygordobil, Daniel Sierra-Lara, Agustin Rivera-Rodriguez, Aloha Meave, Erick Alexanderson Rosas
Journal: Journal of the American College of Cardiology (2017)
Induction of endothelial nitric oxide synthase expression by melanoma cells sensitizes tumor endothelium to TNF-driven apoptosis
Authors: S. Mocellin, M. Provenzano, C. R. Rossi, P. Pilati, D. Nitti, M. Lise
Journal: Journal of Clinical Oncology (2004)

9669 Background. Despite the well known antiblastic properties of TNFa in the clinical setting, the cascade of molecular events leading to the cytokine-mediated tumor regression is still incompletely elucidated. We investigated the role of endothelial nitric oxide synthase (eNOS) in determining the tumor selective activity of TNFa. Materials and methods. Using quantitative real time PCR, eNOS gene levels were measured in melanoma intradermal metastases and normal skin biopsies obtained from twelve patients before undergoing TNFa-based isolated limb perfusion. The ability of melanoma cells to affect eNOS transcription by endothelial cells (EC) was tested in vitro. TNFa-induced apoptosis of EC was evaluated in the presence of NOS inhibitors. Results. Endothelial NOS transcript abundance resulted significantly greater in tumor than normal skin samples. Furthermore, eNOS mRNA expression by tumor was higher in complete than in partial/minimal responders. In vitro, melanoma cells supernatant induced eNOS gene expression by EC. NOS inhibition slowed EC proliferation and, if induced before TNFa administration, decreased the rate of cytokine-mediated apoptosis of EC. Conclusions. These findings suggest that tumor endothelium may be selectively targeted by TNFa because of its high levels of eNOS expression. The co-administration of NOS inhibitors might represent a promising therapeutic approach to combine pro-apoptotic and anti-proliferative effects while targeting tumor endothelium. These observations may have important prognostic and therapeutic implications in the clinical setting. No significant financial relationships to disclose.
MULTIDISCIPLINARY CARDIOVASCULAR TEAM REVIEW CAPTURES PRECLINICAL DISEASE
Authors: Mariam Kashani, Arn Eliasson, Elaine Walizer, Claire Fuller, Nancy Tschiltz, Ellen Turner, Marilyn Grunewald, Joy Halsey, Renata J.M. Engler, Todd Villines, Marina Vernalis
Journal: Journal of the American College of Cardiology (2017)
Novel chemosensitivity assay for targeting cancer stem-like cells in brain tumors.
Authors: Pier Paolo Claudio, Sarah E Mathis, Rounak Nande, Anthony Alberico, Walter Neto, Logan Lawrence, James Denvir, Gerrit A. Kimmey, Aneel A. Chowdhary, Maria R. B. Tria Tirona, Mark Jeffrey Mogul, Terrence D Julien, Rida S Mazagri, Gerald Oakley, Krista L Denning, Thomas Dougherty, Linda Brown, Jagan Valluri
Journal: Journal of Clinical Oncology (2014)

e13012 Background: Cancer stem-like cells (CSLCs) in primary brain tumors can resist certain chemotherapies, thereby causing relapse of the disease. Thus, development of a test that identifies the most effective chemotherapy management offers great promise for personalized anticancer treatments. Methods: We have developed an ex vivo chemosensitivity assay (ChemoID) designed to predict the sensitivity and resistance of CSLCs and bulk of tumor cells of a given patient's solid tumor to a variety of chemotherapy agents by measuring cellular viability following chemotherapy treatments at clinically relevant doses. In a retrospective study of 7 patients with malignancies of the central nervous system (2 Ependymoma Grade III, 4 Glioblastoma Grade IV, and 1 Medulloblastoma), we assessed the accuracy of the ChemoID assay by comparing the results to the actual clinical response. Tumors were classified as responsive (60-100% cell kill), intermediately responsive (30-60% cell kill), and non-responsive (0-30% cell kill) to chemotherapy. Treatment selection was blinded to assay results. MRI and CT scan determined response to therapy. Additionally, the effectiveness of the ex vivo ChemoID predicted drugs and clinical response was compared to the response of patients' derived xenografts treated with the most effective and least effective ChemoID predicted drugs. Results: The ChemoID assay performed on the CSLCs and tumor bulk produced a correct prediction in 7 out of 7 cases (p=0.02857, Fisher's Exact Test; PPV=100% (3/3), NPV=100% (4/4) when compared to the drugs received. Results from animal studies conducted in 3 patients' derived xenografts were also found in agreement with the clinical outcomes. Conclusions: An assay such as ChemoID that measures cell death of CSLCs and bulk of tumor cells appears to be beneficial in selecting specific standard chemotherapy agents ex vivo for patients with malignancies of the central nervous system.
Clinical characteristics and outcome of late relapse after cisplatin-based chemotherapy of germ cell tumor. An update
Authors: A. Gerl, M. Hentrich, N. Weber, M. Schlemmer, R. Hartenstein, W. Hiddemann
Journal: Journal of Clinical Oncology (2004)

4529 Background: Late relapse of germ cell tumor (GCT) is defined as recurrence after an interval of more than 2 years from initial therapy. Data on clinical characteristics and outcome of patients with late relapses of GCT are sparse. Methods: The charts of 37 patients treated for late relapse after cisplatin-based chemotherapy for GCT from 1983 through 2002 were reviewed (non-seminoma n=36, pure seminoma n=1). Results: Time to late relapse ranged from 25 to 191 months (median 66 months; > 5 years n=21 [57%], > 10 years n=5 [14%]). Tumor marker AFP was elevated in 21 of 36 patients (58%), HCG in 6 cases (17%). The most frequently involved site was the retroperitoneum n=17 (46%) followed by mediastinum n=9 (24%), pelvis, retrocrural space, neck, lung and liver (each site n=4 [11%]). 5 patients (14%) had a late relapse with pure teratoma. 2 patients refused any treatment, 24 patients (65%) underwent chemotherapy as initial treatment for late relapse, 11 patients (30%) surgery. After initial therapy for late relapse 19 patients (51%) achieved no evidence of diesase (NED) status, 9 of whom relapsed again (5 with a second late relapse). After a median follow-up of 52 months (range, 9–168 months) 17 patients (46%) are alive with NED (15 of 27 patients [56%] with disease at one antomic site only), 10 patients (27%) continuously and 7 (19%) after further treatment. 30 patients underwent chemotherapy for management of late relapse or subsequent recurrence, 3 (10%) of whom achieved a durable NED status to chemotherapy alone (1 patient to oral etoposide after failure of high-dose chemotherapy). Conclusions: Resectable disease at one anatomic site is a predictor for favorable outcome of treatment for late relapse. Durable response to chemotherapy alone is rare but occurs even in heavily pretreated patients. As the risk for second late relapse is substantial, lifetime follow-up is necessary. No significant financial relationships to disclose.
Homozygous Antithrombin Deficient Type II (99Leu to Phe mutation): Description of a Successful Outcome during Pregnancy
Authors: C. Muñoz Novas, C. Pascual, J. Sanchez, A. Rodriguez, G. Pérez, M. Kwon, A. Gomez-Pineda, J. Corral, J. Diez-Martín
Journal: Blood (2008)
CAN CHA2DS2-VASC SCORE BE USED AS A PREDICTOR OF CONTRAST INDUCED NEPHROPATHY AFTER CARDIAC CATHETERIZATION?
Authors: Yub Raj Sedhai, Santosh Timalsina, Ankush Asija, Tatvam Choksi, Waseem Ahangar, David Gevorgyan, Reshma Golamari, Madhura Borikar, Tawseef Dar, Joseph Alukal, Jose Missri
Journal: Journal of the American College of Cardiology (2017)
SYNTAX SCORE II IN PATIENTS WITH CORONARY ARTERY DISEASE UNDERGOING MITRACLIP: A NEW APPROACH TO RISK STRATIFICATION
Authors: Slayman Nabih Obeid, Fabian Nietlispach, Adrian Attinger-Toller, Hector Rodriguez, Maurizio Taramasso, Francesco Maisano
Journal: Journal of the American College of Cardiology (2017)
Outcome of the ALL-96 Protocol for Childhood ALL from the Kyushu-Yamaguchi Children’s Cancer Study Group.
Authors: Yoshihisa Nagatoshi, Aiko Suminoe, Akinobu Matsuzaki, Koichiro Ueda, Hiroko Inada, Kiyoshi Kawakami, Fumio Yanai, Hideki Nakayama, Hiroshi Moritake, Nobuyoshi Itonaga, Hiroshi Ayukawa, Kyoko Fujita, Yoshifumi Kawano, Jun Okamura
Journal: Blood (2005)
MID FEMORAL HEAD IS NOT THE IDEAL FLUROSCOPIC LANDMARK FOR COMMON FEMORAL ARTERY PUNCTURE
Authors: Prabhakaran Gopalakrishnan, Pradeep Manoharan, Chander Shekhar, Sharan Rufus Ponniah, Muhammad Chaudhry, Pradeepto Ghosh, Digant Bhatt, Ira Friedlander, Nagapradeep Nagajothi
Journal: Journal of the American College of Cardiology (2017)
Effect of short-duration chemoimmunotherapy plus radioimmunotherapy on response rates in relapsed follicular lymphoma: A U.K. NCRI Lymphoma Group Study, CR UK/07/038.
Authors: Timothy M Illidge, Andrew T. Bates, Andrew John Davies, Ruth Pettengell, Barry Andrews, Louise Dent, Grace Hampson, Maureen Zivanovic, Eve Gallop-Evans, John A. Radford, Peter W. M. Johnson
Journal: Journal of Clinical Oncology (2012)

8056 Background: Radioimmunotherapy (RIT) and rituximab (R) maintenance have been investigated after chemotherapy (CT) or R-CT in first line treatment of follicular lymphoma (FL), but less is known about the efficacy of RIT after R-CT in relapsed FL. This phase II study was conducted to examine efficacy and safety of abbreviated R-CT followed by 90 Y Ibritumomab tiuxetan in patients with recurrent FL. Methods: Patients (pts) had FL, at 1 st or 2 nd relapse after response to R-CT or CT alone. All had WHO/ECOG performance status ≤2, and adequate bone marrow (BM), kidney, liver and cardiac function. BM involvement by lymphoma had to be &lt;25% prior to infusion of 90 Y Ibritumomab tiuxetan, but could be higher at study entry. Pts received 3 cycles of either R-CHOP or R-CVP, followed by 90 Y Ibritumomab tiuxetan (15MBq/Kg, maximum 1200 MBq). No maintenance R was given. Results: 52 pts were enrolled from 6/2008 to 7/2010. Median age was 62 years (range 31-87). 46% had high FLIPI score at entry, 31% intermediate. 80% were at 1st recurrence. Median duration of best prior remission was 27.7 months. 65% pts had previously received R and 25% doxorubicin. 71% pts had R-CHOP and 29% R-CVP, prior to RIT. Overall response rate (ORR) after 3 cycles R-CT was 94% (CR/CRu 10%) and after RIT ORR 96% (CR/CRu 28%). Grade 3/4 thrombocytopenia occurred in 58% pts (median duration 16 days): 3/52 pts after R-CT and 27/52 after RIT. Grade 3/4 neutropenia occurred in 62% pts: 15/52 pts after R-CT and 27/52 after RIT. 5 pts had a total 8 grade 3 infections, only 1 attributable to RIT. 6 pts required platelets and 4 red cell transfusions. 1 pt developed myelodysplasia 10 months after 90 Y Ibritumomab tiuxetan, but no other second malignancy was recorded. PFS was 31.4 months (95% CI 15.8 - not reached). There was no difference in PFS according to FLIPI score at entry or reinduction CT (R-CHOP vs R-CVP). Pts with CR/CRu following RIT showed a trend to improved PFS compared to those with PR (12 month PFS 90% versus 63%, p=0.06). Conclusions: Abbreviated R-CT and consolidation with 90 Y Ibritumomab tiuxetan is an option for pts with recurrent FL, with responses of comparable duration to those seen after a full course R-CHOP.
Inhibition of JAK2/STAT3 Pathway Leads to Apoptosis in Chronic Lymphocytic Leukemia Cells
Authors: Filippo Severin, Federica Frezzato, Veronica Martini, Flavia Raggi, Valentina Trimarco, Leonardo Martinello, Andrea Visentin, Monica Facco, Gianpietro Semenzato, Livio Trentin
Journal: Blood (2016)
Construction and characterization of novel CD33/CD3 tandem diabodies (TandAbs) for the treatment of acute myeloid leukemia (AML).
Authors: Uwe Reusch, Kimberly H. Harrington, Chelsea J. Gudgeon, Ivica Fucek, Kristina Ellwanger, Michael Weichel, Stefan Knackmuss, Eugene Zhukovsky, Judith A. Fox, Jeanmarie Guenot, Roland B. Walter
Journal: Journal of Clinical Oncology (2015)

7067 Background: CD33 had been validated as an AML target in randomized studies of the antibody-drug conjugate, gemtuzumab ozogamicin (GO) in a subset of patients, but currently explored CD33-targeted therapeutics are ineffective in many patients. Here, we explored the potential therapeutic activity in AML of a series of novel CD33/CD3-directed tandem diabodies (TandAbs). These tetravalent bispecific antibodies comprised of single chain antibody variable fragments (scFv) have avidity due to two binding sites for each antigen and attractive pharmacokinetics due to a molecular size that is larger than the renal clearance threshold. Methods: CD33/CD3 TandAbs were generated from humananti-CD33 and anti-CD3 scFv domains and expressed in CHO cells. Binding affinities of purified TandAbs were determined via flow cytometry. T-cell activation was assessed via quantitation of CD25 and CD69 on T-cells. Cytotoxic properties of TandAbs against CD33+ AML cell lines and primary specimens from adults with AML, selected across the entire cytogenetic/molecular disease spectrum, were determined in 48-hour assays in the presence of healthy donor T-cells. Results: Our studies demonstrated that CD33/CD3 TandAbs induced potent cytolysis of CD33+ AML cell lines and patient-derived AML specimens at pM concentrations. Their cytotoxic effect required the presence of T-cells and was quantitatively dependent on the concentration of the TandAb as well as the effector-to-target (E:T) cell ratio. In a series of 29 primary AML specimens, high-affinity CD33/CD3-directed TandAbs were broadly active in vitro, even in leukemias with low CD33 expression, with similar activity profiles in specimens from patients with newly diagnosed AML and those with relapsed or refractory disease. Conclusions: CD33/CD3 TandAbs have potent and selective cytotoxicity for CD33+ AML cells that is independent of disease stage. Our findings identified several TandAbs that merit further study as targeted AML therapeutics.