Medicine and Health Sciences Commons^™

Evaluation Of A Technology-Based Survivor Care Plan For Breast Cancer Survivors: Pre-Post Pilot Study., Talya Laufer, Bryan Lerner, Anett Petrich, Anna Quinn, Leah Ernst, Alicin Roop, Janet Knoblauch, Nick C. Leasure, Rebecca J. Jaslow, Sarah Hegarty, Amy Leader, Andrea Barsevick

Department of Medical Oncology Faculty Papers

BACKGROUND: As of 2016, almost 16 million individuals were cancer survivors, including over 3.5 million survivors of breast cancer. Because cancer survivors are living longer and have unique health care needs, the Institute of Medicine proposed a survivor care plan as a way to alleviate the many medical, emotional, and care coordination problems of survivors.

OBJECTIVE: This pilot study for breast cancer survivors was undertaken to: (1) examine self-reported changes in knowledge, confidence, and activation from before receipt to after receipt of a survivor care plan; and (2) describe survivor preferences for, and satisfaction with, a technology-based survivor care plan. …

A Case Of Ccdc6-Ret Fusion Mutation In Adult Acute Lymphoblastic Leukemia (All), A Known Activating Mutation Reported In All, Mateo Mejia Saldarriaga, Amir Steinberg, Eric A. Severson, Adam Binder

Department of Medical Oncology Faculty Papers

We report the case of a patient with B-Cell Acute Lymphoblastic Leukemia (ALL) who was found to harbor a gene fusion involving the CCDC6 and RET genes. Although the RET mutations have been identified before in othermalignancies, and it is thought to represent a driver mutation in these neoplasms, it has yet to be described in ALL. The identification of known fusion genes conferring activating tyrosine kinase activity in neoplasms can suggest potential therapeutic role of tyrosine kinase inhibitors (TKI), an approach that has been exploited in several other fusion genes.

Phase Iii Randomized Trial Of Chemotherapy With Or Without Bevacizumab In Patients With Recurrent Or Metastatic Head And Neck Cancer., Athanassios Argiris, Shuli Li, Panayiotis Savvides, James P. Ohr, Jill Gilbert, Marshall A. Levine, Arnab Chakravarti, Missak Haigentz, Nabil F. Saba, Chukwuemeka V. Ikpeazu, Charles J. Schneider, Harlan A. Pinto, Arlene A. Forastiere, Barbara Burtness

Department of Medical Oncology Faculty Papers

PURPOSE: We evaluated the addition of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).

PATIENTS AND METHODS: Patients with chemotherapy-naïve (or with prior platinum as part of multimodal therapy completed ≥ 4 months earlier) recurrent or metastatic SCCHN were randomly assigned to receive a platinum-based chemotherapy doublet with or without bevacizumab 15 mg/kg given intravenously every 3 weeks until disease progression. Chemotherapy could be discontinued after six cycles if a maximum response was achieved.

RESULTS: The study randomly assigned 403 patients. …

Efficient And Robust Nk-Cell Transduction With Baboon Envelope Pseudotyped Lentivector., Aurelien B L Colamartino, William Lemieux, Panojot Bifsha, Simon Nicoletti, Nitin Chakravarti, Joaquín Sanz, Hugo Roméro, Silvia Selleri, Kathie Béland, Mélanie Guiot, Camille Tremblay-Laganière, Renée Dicaire, Luis Barreiro, Dean A Lee, Els Verhoeyen, Elie Haddad

Department of Medical Oncology Faculty Papers

NK-cell resistance to transduction is a major technical hurdle for developing NK-cell immunotherapy. By using Baboon envelope pseudotyped lentiviral vectors (BaEV-LVs) encoding eGFP, we obtained a transduction rate of 23.0 ± 6.6% (mean ± SD) in freshly-isolated human NK-cells (FI-NK) and 83.4 ± 10.1% (mean ± SD) in NK-cells obtained from the NK-cell Activation and Expansion System (NKAES), with a sustained transgene expression for at least 21 days. BaEV-LVs outperformed Vesicular Stomatitis Virus type-G (VSV-G)-, RD114- and Measles Virus (MV)- pseudotyped LVs (p < 0.0001). mRNA expression of both BaEV receptors, ASCT1 and ASCT2, was detected in FI-NK and NKAES, with higher expression in NKAES. Transduction with BaEV-LVs encoding for CAR-CD22 resulted in robust CAR-expression on 38.3 ± 23.8% (mean ± SD) of NKAES cells, leading to specific killing of NK-resistant pre-B-ALL-RS4;11 cell line. Using a larger vector encoding a dual CD19/CD22-CAR, we were able to transduce and re-expand dual-CAR-expressing NKAES, even with lower viral titer. These dual-CAR-NK efficiently killed both CD19KO- and CD22KO-RS4;11 cells. Our results suggest that BaEV-LVs may efficiently enable NK-cell biological studies and translation of NK-cell-based immunotherapy to the clinic.

Gilteritinib Or Chemotherapy For Relapsed Or Refractory Flt3-Mutated Aml, Alexander E. Perl, Giovanni Martinelli, Jorge E. Cortes, Andreas Neubauer, Ellin Berman, Stefania Paolini, Pau Montesinos, Maria R. Baer, Richard A. Larson, Celalettin Ustun, Francesco Fabbiano, Harry P. Erba, Antonio Di Stasi, Robert Stuart, Rebecca Olin, Margaret Kasner, Fabio Ciceri, Wen-Chien Chou, Nikolai Podoltsev, Christian Recher, Hisayuki Yokoyama, Naoko Hosono, Sung-Soo Yoon, Je-Hwan Lee, Timothy Pardee, Amir T. Fathi, Chaofeng Liu, Nahla Hasabou, Xuan Liu, Erkut Bahceci, Mark J. Levis

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (AML) with mutations in the FMS-like tyrosine kinase 3 gene (FLT3) infrequently have a response to salvage chemotherapy. Gilteritinib is an oral, potent, selective FLT3 inhibitor with single-agent activity in relapsed or refractory FLT3-mutated AML.

METHODS: In a phase 3 trial, we randomly assigned adults with relapsed or refractory FLT3-mutated AML in a 2:1 ratio to receive either gilteritinib (at a dose of 120 mg per day) or salvage chemotherapy. The two primary end points were overall survival and the percentage of patients who had complete remission …

Relating The Gut Metagenome And Metatranscriptome To Immunotherapy Responses In Melanoma Patients., Brandilyn A. Peters, Melissa Wilson, Una Moran, Anna Pavlick, Allison Izsak, Todd Wechter, Jeffrey S. Weber, Iman Osman, Jiyoung Ahn

Department of Medical Oncology Faculty Papers

BACKGROUND: Recent evidence suggests that immunotherapy efficacy in melanoma is modulated by gut microbiota. Few studies have examined this phenomenon in humans, and none have incorporated metatranscriptomics, important for determining expression of metagenomic functions in the microbial community.

METHODS: In melanoma patients undergoing immunotherapy, gut microbiome was characterized in pre-treatment stool using 16S rRNA gene and shotgun metagenome sequencing (n = 27). Transcriptional expression of metagenomic pathways was confirmed with metatranscriptome sequencing in a subset of 17. We examined associations of taxa and metagenomic pathways with progression-free survival (PFS) using 500 × 10-fold cross-validated elastic-net penalized Cox regression.

RESULTS: Higher …

Clinical, Cytogenetic, And Molecular Findings In Two Cases Of Variant T(8;21) Acute Myeloid Leukemia (Aml)., Lindsay Wilde, Jillian Cooper, Zi-Xuan Wang, Jinglan Liu

Department of Medical Oncology Faculty Papers

t(8;21)(q22;q22) is present in ~5–10% of patients with de novo acute myeloid leukemia (AML) and is associated with a better overall prognosis. Variants of the t(8;21) have been described in the literature, however, their clinical and prognostic significance has not been well-characterized. Molecular profiling of these cases has not previously been reported but may be useful in better defining the prognosis of this subset of patients. We present two cases of variant t(8;21) AML including clinical, cytogenetic, and molecular data.

Decreasing Time To Initiation Of Chemotherapy For Patients Electively Admitted To A Hematologic Malignancy Service., Jose N Galeas, Stuart Packer, Roy Browne, Susan Sakalian, Adam F. Binder

Department of Medical Oncology Faculty Papers

Background: Delays in initiating elective inpatient chemotherapy can decrease patient satisfaction and increase length of stay. At our institution, we observed that 86% of patients admitted for elective chemotherapy experienced a delay (greater than 6 hours) with a median time to chemotherapy of 18.9 hours. We developed a process improvement initiative to improve time to chemotherapy for elective chemotherapy admissions.

Methods: Our outcome measure was time from admission to chemotherapy administration in patients admitted for elective chemotherapy. Process measures were identified and monitored. We collected baseline data and utilized performance improvement tools to identify key drivers. We focused on these …

Excision Repair Cross-Complementing Group-1 (Ercc1) Induction Kinetics And Polymorphism Are Markers Of Inferior Outcome In Patients With Colorectal Cancer Treated With Oxaliplatin., Devika Rao, Atrayee Basu Mallick, Titto Augustine, Cecilia Daroqui, Jeeshan Jiffry, Amartej Merla, Imran Chaudhary, Raviraja Seetharam, Arjun Sood, Srikanth Gajavelli, Santiago Aparo, Lakshmi Rajdev, Andreas Kaubisch, Jennifer Chuy, Abdissa Negassa, John M. Mariadason, Radhashree Maitra, Sanjay Goel

Department of Medical Oncology Faculty Papers

Background: ERCC1, a component of nucleotide excision repair pathway, is known to repair DNA breaks induced by platinum drugs. We sought to ascertain if ERCC1 expression dynamics and a single nucleotide polymorphism (SNP) rs11615 are biomarkers of sensitivity to oxaliplatin therapy in patients with colorectal cancer (CRC).

Methods: Western blot and qPCR for ERCC1 expression was performed from PBMCs isolated from patients receiving oxaliplatin-based therapy at specified timepoints. DNA was also isolated from 59 biorepository specimens for SNP analysis. Clinical benefit was determined using progression free survival (PFS) for metastatic CRC.

Results: ERCC1 was induced in PBMC in response to …

Editorial: Cancer Ecosystems., Ubaldo E. Martinez-Outshoorn, Mireia Bartrons, Ramon Bartrons

Department of Medical Oncology Faculty Papers

No abstract provided.

Outcomes Of Haploidentical Vs Matched Sibling Transplantation For Acute Myeloid Leukemia In First Complete Remission., Armin Rashidi, Mehdi Hamadani, Mei-Jie Zhang, Hai-Lin Wang, Hisham Abdel-Azim, Mahmoud Aljurf, Amer Assal, Ashish Bajel, Asad Bashey, Minoo Battiwalla, Amer M. Beitinjaneh, Nelli Bejanyan, Vijaya Raj Bhatt, Javier Bolaños-Meade, Michael Byrne, Jean-Yves Cahn, Mitchell Cairo, Stefan Ciurea, Edward Copelan, Corey Cutler, Andrew Daly, Miguel-Angel Diaz, Nosha Farhadfar, Robert P. Gale, Siddhartha Ganguly, Michael R. Grunwald, Theresa Hahn, Shahrukh Hashmi, Gerhard C. Hildebrandt, H. Kent Holland, Nasheed Hossain, Christopher G Kanakry, Mohamed A. Kharfan-Dabaja, Nandita Khera, Yener Koc, Hillard M. Lazarus, Jong-Wook Lee, Johan Maertens, Rodrigo Martino, Joseph Mcguirk, Reinhold Munker, Hemant S. Murthy, Ryotaro Nakamura, Sunita Nathan, Taiga Nishihori, Neil D. Palmisiano, Sagar Patel, Joseph Pidala, Rebecca Olin, Richard F. Olsson, Betul Oran, Olov Ringden, David Rizzieri, Jacob Rowe, Mary Lynn Savoie, Kirk R. Schultz, Sachiko Seo, Brian C. Shaffer, Anurag Singh, Melhem Solh, Keith Stockerl-Goldstein, Leo F. Verdonck, John Wagner, Edmund K. Waller, Marcos De Lima, Brenda M. Sandmaier, Mark Litzow, Dan Weisdorf, Rizwan Romee, Wael Saber

Department of Medical Oncology Faculty Papers

HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy–based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor–based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs …

Extreme Peripheral Blood Plasmacytosis Mimicking Plasma Cell Leukemia As A Presenting Feature Of Angioimmunoblastic T-Cell Lymphoma (Aitl)., Kelsey Sokol, Saritha Kartan, William T. Johnson, Onder Alpdogan, Neda Nikbakht, Bradley M. Haverkos, Jerald Z. Gong, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

Angioimmunoblastic T-cell lymphoma (AITL) is one of four major subtypes of nodal peripheral T cell lymphoma, characterized by its cell of origin, the follicular helper T-cell (TFH). Patients typically present with prominent constitutional (B) symptoms, generalized lymphadenopathy, hepatosplenomegaly, cytopenias, and rash. Here we present a case of a 62-year-old male with progressive cervical adenopathy, fevers and weight loss presenting with extreme polyclonal plasmacytosis and high plasma EBV viral load. While the initial presentation appeared to mimic plasma cell leukemia or severe infection, lymph node biopsy and bone marrow biopsy confirmed a diagnosis of AITL. This case highlights the heterogeneity of …

Laryngeal Preservation Strategies In Locally Advanced Laryngeal And Hypopharyngeal Cancers., Athanassios Argiris, Jean Louis Lefebvre

Department of Medical Oncology Faculty Papers

For long, the treatment of locoregionally advanced laryngeal and hypopharyngeal squamous cell cancers (SCC) consisted of either total laryngectomy (TL) or definitive radiotherapy (RT). The development of induction cisplatin plus 5-fluorouracil (PF) and the correlation between chemosensitivity and radiosensitivity in previously untreated patients opened a new era of treatment aiming at laryngeal preservation (LP). The fundamental concept was to employ induction PF in order to select patients for subsequent treatment with either TL or RT according to tumor response to PF. The first two trials (VALGSG for laryngeal SCC and EORTC 24891 for hypopharyngeal SCC) concluded that such an approach …

Grfs And Crfs In Alternative Donor Hematopoietic Cell Transplantation For Pediatric Patients With Acute Leukemia., Rohtesh S. Mehta, Shernan G Holtan, Tao Wang, Michael T. Hemmer, Stephen R. Spellman, Mukta Arora, Daniel R. Couriel, Amin M. Alousi, Joseph Pidala, Hisham Abdel-Azim, Ibrahim Ahmed, Mahmoud Aljurf, Medhat Askar, Jeffery J. Auletta, Vijaya Bhatt, Christopher Bredeson, Saurabh Chhabra, Shahinaz Gadalla, James Gajewski, Robert Peter Gale, Usama Gergis, Peiman Hematti, Gerhard C. Hildebrandt, Yoshihiro Inamoto, Carrie Kitko, Pooja Khandelwal, Margaret L. Macmillan, Navneet Majhail, David I. Marks, Parinda Mehta, Taiga Nishihori, Richard F. Olsson, Attaphol Pawarode, Miguel Angel Diaz, Tim Prestidge, Muna Qayed, Hemalatha Rangarajan, Olle Ringden, Ayman Saad, Bipin N. Savani, Sachiko Seo, Ami Shah, Niketa Shah, Kirk R. Schultz, Melhem Solh, Thomas Spitzer, Jeffrey Szer, Takanori Teshima, Leo F Verdonck, Kirsten M. Williams, Baldeep Wirk, John Wagner, Jean A. Yared, Daniel J. Weisdorf

Department of Medical Oncology Faculty Papers

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P < .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P < .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors. © 2019 American Society of Hematology. All rights reserved.

Management Of Cancer-Associated Anemia With Erythropoiesis-Stimulating Agents: Asco/Ash Clinical Practice Guideline Update., Julia Bohlius, Kari Bohlke, Roberto Castelli, Benjamin Djulbegovic, Maryam B Lustberg, Massimo Martino, Giannis Mountzios, Namrata Peswani, Laura Porter, Tiffany N. Tanaka, Gianluca Trifirò, Hushan Yang, Alejandro Lazo-Langner

Department of Medical Oncology Faculty Papers

PURPOSE: To update the American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer.

METHODS: PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs in patients with cancer published from January 31, 2010, through May 14, 2018. For biosimilar ESAs, the literature search was expanded to include meta-analyses and RCTs in patients with cancer or chronic kidney disease and cohort studies in patients with cancer due to limited RCT evidence in the cancer setting. ASCO and ASH convened an Expert Panel to …

The Role Of Inhibition Of Apoptosis In Acute Leukemias And Myelodysplastic Syndrome., Amanda Mcbride, Sarah Houtmann, Lindsay Wilde, Carlos Vigil, Christine M. Eischen, Margaret Kasner, Neil Palmisiano

Department of Medical Oncology Faculty Papers

Avoidance of apoptosis is a key mechanism that malignancies, including acute leukemias and MDS, utilize in order to proliferate and resist chemotherapy. Recently, venetoclax, an inhibitor of the anti-apoptotic protein BCL-2, has been approved for the treatment of upfront AML in an unfit, elderly population. This paper reviews the pre-clinical and clinical data for apoptosis inhibitors currently in development for the treatment of AML, ALL, and MDS.

Targeting The Bcl-2 Family In B Cell Lymphoma., Clare M. Adams, Sean Clark-Garvey, Pierluigi Porcu, Christine M. Eischen

Department of Medical Oncology Faculty Papers

Although lymphoma is a very heterogeneous group of biologically complex malignancies, tumor cells across all B cell lymphoma subtypes share a set of underlying traits that promote the development and sustain malignant B cells. One of these traits, the ability to evade apoptosis, is essential for lymphoma development. Alterations in the Bcl-2 family of proteins, the key regulators of apoptosis, is a hallmark of B cell lymphoma. Significant efforts have been made over the last 30 years to advance knowledge of the biology, molecular mechanisms, and therapeutic potential of targeting Bcl-2 family members. In this review, we will highlight the …