Hematology Commons^™

Clinical And Genomic Profile Of Primary Cranial Neurolymphomatosis, Emily B Wolf, Robin Imperial, Liuyan Jiang, Amit K Agarwal, Han W Tun

Faculty, Staff and Student Publications

Primary cranial neurolymphomatosis (PCNL) is a rare subtype of primary CNS lymphoma (PCNSL) in which infiltrative lymphomatous involvement is confined to cranial nerves. Here, we report a case of PCNL with successful genomic profiling. A 57-year-old male had a lengthy prediagnostic phase spanning approximately 30 months, characterized by multiple episodes of cranial neuropathies managed by steroids. At the time of diagnosis, the patient had right-sided cranial neuropathies involving cranial nerves (CN) V, VI, and VII. Pathological findings of the right cavernous lesion biopsy were consistent with large B-cell lymphoma-infiltrating nerve fibers. The clinical course was aggressive and refractory, characterized by …

Digital Twin Mathematical Models Suggest Individualized Hemorrhagic Shock Resuscitation Strategies, Jeremy W Cannon, Danielle S Gruen, Ruben Zamora, Noah Brostoff, Kelly Hurst, John H Harn, Fayten El-Dehaibi, Zhi Geng, Rami Namas, Jason L Sperry, John B Holcomb, Bryan A Cotton, Jason J Nam, Samantha Underwood, Martin A Schreiber, Kevin K Chung, Andriy I Batchinsky, Leopoldo C Cancio, Andrew J Benjamin, Erin E Fox, Steven C Chang, Andrew P Cap, Yoram Vodovotz

Faculty, Staff and Student Publications

BACKGROUND: Optimizing resuscitation to reduce inflammation and organ dysfunction following human trauma-associated hemorrhagic shock is a major clinical hurdle. This is limited by the short duration of pre-clinical studies and the sparsity of early data in the clinical setting.

METHODS: We sought to bridge this gap by linking preclinical data in a porcine model with clinical data from patients from the Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) study via a three-compartment ordinary differential equation model of inflammation and coagulation.

RESULTS: The mathematical model accurately predicts physiologic, inflammatory, and laboratory measures in both the porcine model and patients, as well …

Prospective Performance Of The Iwg-2023 Criteria And Ipss-M In A Phase 2 Trial Of Guadecitabine For Higher-Risk Mds Or Cmml, Samuel Urrutia, Prithviraj Bose, Yesid Alvarado, Gautam Borthakur, Farhad Ravandi, Naval Daver, Naveen Pemmaraju, Elias Jabbour, Koichi Takahashi, Tapan Kadia, Courtney Dinardo, Steven Kornblau, Rashmi Kanagal-Shamanna, Xuelin Huang, Kristy Bodden, Hagop Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Guadecitabine (SGI-110) is a dinucleotide form of decitabine that has been studied in myelodysplastic syndrome (MDS) and acute myeloid leukemia. Here, we present the results of a single-center phase 2 trial of this agent for patients with higher-risk MDS or chronic myelomonocytic leukemia (CMML). Guadecitabine was administered at a dose of 60 mg/m2 subcutaneously for 5 days. Of 100 enrolled patients, 82% had MDS. The median age was 69 years, and International Prognostic Scoring System (IPSS) was intermediate-2 in 78% and high in 14%. Thirty-eight percent had complex cytogenetics, and 32% had TP53 mut . By the International Working Group …

Stat5b Mutations In Myeloid Neoplasms Differ By Disease Subtypes But Characterize A Subset Of Chronic Myeloid Neoplasms With Eosinophilia And/Or Basophilia, C Cameron Yin, Wayne Tam, Serena M Walker, Amandeep Kaur, Madhu M Ouseph, Wei Xie, Olga K Weinberg, Peng Li, Zhuang Zuo, Mark J Routbort, Simon Chen, L Jeffrey Medeiros, Tracy I George, Attilio Orazi, Daniel A Arber, Adam Bagg, Robert P Hasserjian, Sa A Wang

Faculty, Staff and Student Publications

STAT5B has been reported as a recurrent mutation in myeloid neoplasms with eosinophilia, but its overall frequency and importance across a spectrum of myeloid neoplasms are largely unknown. We conducted a multicenter study on a series of 82 myeloid neoplasms with STAT5B mutations detected by next-generation sequencing. The estimated frequency of STAT5B mutations in myeloid neoplasms was low, <0.5%, but mutations were detected in all categories of such neoplasms, including myelodysplastic syndrome (MDS, 28%), acute myeloid leukemia (AML, 26%), myelodysplastic/myeloproliferative neoplasm (MDS/MPN, 18%), Philadelphia chromosome-negative classic MPN (12%), systemic mastocytosis (1%), and, with a notably high frequency, chronic eosinophilic leukemia, not otherwise specified (CEL-NOS, 15%). STAT5B mutations occurred preferentially in the SH2 domain (95%), involved 12 different codons, with the N642H hotspot being the most common (78%). Co-mutations were present in all cases and clonal hierarchy analysis showed that STAT5B mutations tended to be subclonal in AML, MPN, and MDS, but frequently dominant/co-dominant in CEL-NOS (83%), followed by MDS/MPN (40%). Across the group, eosinophilia and/or basophilia were common (41%), frequently observed in cases in which STAT5B mutations were detected at initial diagnosis (P<0.0001), with a high variant allele frequency (median 42.5%, P=0.0001), as a dominant/ co-dominant clone (P<0.0001), involving the canonical N642H (P=0.0607), and associated with fewer co-mutations (P=0.0009). Our data show that the characteristics and importance of a STAT5B mutation differ among myeloid neoplasms, but if present as a dominant mutation and detected at initial diagnosis, it appears to be a driver mutation in a subgroup of chronic myeloid neoplasms, preferentially promoting a proliferation of eosinophils and basophils.

A Multicenter Study Of Venetoclax-Based Treatment For Patients With Richter Transformation Of Chronic Lymphocytic Leukemia, Paul J Hampel, Mahesh Swaminathan, Kerry A Rogers, Erin M Parry, Jan A Burger, Matthew S Davids, Wei Ding, Alessandra Ferrajoli, Jonathan M Hyak, Nitin Jain, Saad S Kenderian, Yucai Wang, William G Wierda, Jennifer A Woyach, Sameer A Parikh, Philip A Thompson

Faculty, Staff and Student Publications

Patients with chronic lymphocytic leukemia (CLL) who develop Richter transformation (RT) have a poor prognosis when treated with chemoimmunotherapy regimens used for de novo diffuse large B-cell lymphoma. Venetoclax, a BCL2 inhibitor, has single-agent efficacy in patients with RT and is potentially synergistic with chemoimmunotherapy. In this multicenter, retrospective study, we evaluated 62 patients with RT who received venetoclax-based treatment outside of a clinical trial, in combination with a Bruton tyrosine kinase inhibitor (BTKi; n=28), rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) (n=13), or intensive chemoimmunotherapy other than R-CHOP (n=21). The best overall and complete response rates were 36%/25%, 54%/46%, and …

Differentiation Syndrome Associated With Treatment With Idh2 Inhibitor Enasidenib: Pooled Analysis From Clinical Trials, Pau Montesinos, Amir T Fathi, Stéphane De Botton, Eytan M Stein, Amer M Zeidan, Yue Zhu, Thomas Prebet, Carlos E Vigil, Iryna Bluemmert, Xin Yu, Courtney D Dinardo

Faculty, Staff and Student Publications

Treatment with enasidenib, a selective mutant isocitrate dehydrogenase isoform 2 (IDH2) inhibitor, has been associated with the development of differentiation syndrome (DS) in patients with acute myeloid leukemia (AML). Studies on the incidence and clinical features of DS are limited in this setting, and diagnosis is challenging because of nonspecific symptoms. This study assessed the incidence, diagnostic criteria, risk factors, and correlation with clinical response of DS based on the pooled analysis of 4 clinical trials in patients with IDH2-mutated AML treated with enasidenib as monotherapy, or in combination with azacitidine or with chemotherapy. Across the total AML population, 67 …

Astrocytic Slc4a4 Regulates Blood-Brain Barrier Integrity In Healthy And Stroke Brains Via A Ccl2-Ccr2 Pathway And No Dysregulation, Qi Ye, Juyeon Jo, Chih-Yen Wang, Heavin Oh, Jiangshan Zhan, Tiffany J Choy, Kyoung In Kim, Angelo D'Alessandro, Yana K Reshetnyak, Sung Yun Jung, Zheng Chen, Sean P Marrelli, Hyun Kyoung Lee

Faculty, Staff and Student Publications

Astrocytes play vital roles in blood-brain barrier (BBB) maintenance, yet how they support BBB integrity under normal or pathological conditions remains poorly defined. Recent evidence suggests that ion homeostasis is a cellular mechanism important for BBB integrity. In the current study, we investigated the function of an astrocyte-specific pH regulator, Slc4a4, in BBB maintenance and repair. We show that astrocytic Slc4a4 is required for normal astrocyte morphological complexity and BBB function. Multi-omics analyses identified increased astrocytic secretion of CCL2 coupled with dysregulated arginine-NO metabolism after Slc4a4 deletion. Using a model of ischemic stroke, we found that loss of Slc4a4 exacerbates …

Ael Transformed From Post-Et Myelofibrosis With A Sinusoidal Pattern, Jak2 Mutation, And Biallelic Tp53 Inactivation, Qing Wei, M James You

Faculty, Staff and Student Publications

No abstract provided.

Profiling The Activity Of The Para-Caspase Malt1 In B-Cell Acute Lymphoblastic Leukemia For Potential Targeted Therapeutic Application, Firas M Safa, Terri Rasmussen, Lorena Fontan, Min Xia, Ari Melnick, Adrian Wiestner, Patricia Lobelle-Rich, Jan A Burger, Yara Mouawad, Hana Safah, Erik K Flemington, Nakhle S Saba

Faculty, Staff and Student Publications

B-cell acute lymphoblastic leukemia (B-ALL) remains a hard-to-treat disease with a poor prognosis in adults. Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a para-caspase required for B-cell receptor (BCR)-mediated NF-κB activation. Inhibition of MALT1 in preclinical models has proven efficacious in many B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma and diffuse large B-cell lymphoma. We sought to examine the role of MALT1 in B-ALL and determine the biological consequences of its inhibition. Targeting MALT1 with both Z-VRPR-fmk and MI-2 efficiently kills B-ALL cells independent of the cell-of-origin (pro, pre, mature) or the presence of the Philadelphia …

Mechanical Venous Thrombectomy For Deep Venous Thrombosis In Cancer Patients: A Single-Center Retrospective Study, Riya M Patel, Koustav Pal, Syed Hadi Ahmed, Joshua D Kuban, Milan Patel, Ketan Shah, Peiman Habibollahi, Zeyad Metwalli, Varshana Gurusamy, Sanjay Gupta, Cristhiam M Rojas-Hernandez, Vahid Afshar-Kharghan, Michael H Kroll, Rahul A Sheth

Faculty, Staff and Student Publications

PURPOSE: Venous thromboembolism (VTE) is a major contributor to the mortality of cancer patients. Mechanical thrombectomy (MT) is an endovascular technique that physically removes a thrombus without thrombolytics. The purpose of this study was to evaluate safety, efficacy, and clinical outcomes following MT for lower extremity DVT in cancer patients.

METHODS: This single-center, retrospective study evaluated outcomes following MT of lower extremity DVT in cancer patients from November 2019 to May 2023. The primary outcome measure was clinical success, defined as a decrease in Villalta score by at least 2 points following the intervention. Secondary outcomes included repeat intervention-free survival …

Safety And Long-Term Survival Results Of The Addition Of Inotuzumab Ozogamicin To The Conditioning Regimen Of Allogeneic Stem Cell Transplantation: A Single-Center Phase 1,2 Trial, Issa F Khouri, Kamal Alzahrani, Hagop Kantarjian, Denái R Milton, Alison M Gulbis, Koji Sasaki, Nitin Jain, Nicholas J Short, Tapan Kadia, May Daher, Hind Rafei, Jin S Im, David Marin, Amanda L Olson, Uday Popat, Muzaffar Qazilbash, Jeremy Ramdial, Gabriela Rondon, Samer Srour, Partow Kebriaei, Elizabeth Shpall, Richard Champlin, Elias J Jabbour

Faculty, Staff and Student Publications

Here we report on the first prospective study evaluating the safety and long-term survival when an escalating dose of inotuzumab ozogamicin (INO) (0.6, 1.2, or 1.8 mg/m2 on day 13) was added to one alkylator-containing conditioning regimen in patients with relapsed CD22 (+) lymphoid malignancies who were candidates for hematopoietic stem cell transplantation (HSCT). Twenty-six patients were enrolled. Six (23%) of these patients entered the phase 1 study: four were treated at an INO dose of 0.6 mg/m2 and two at dose of 1.2 mg/m2. None of these patients experienced dose-limiting toxicities. The remaining 20 (77%) patients entered the phase …

Proteomics For Optimizing Therapy In Acute Myeloid Leukemia: Venetoclax Plus Hypomethylating Agents Versus Conventional Chemotherapy, Eduardo Sabino De Camargo Magalhães, Stefan Edward Hubner, Brandon Douglas Brown, Yihua Qiu, Steven Mitchell Kornblau

Faculty, Staff and Student Publications

The use of Hypomethylating agents combined with Venetoclax (VH) for the treatment of Acute Myeloid Leukemia (AML) has greatly improved outcomes in recent years. However not all patients benefit from the VH regimen and a way to rationally select between VH and Conventional Chemotherapy (CC) for individual AML patients is needed. Here, we developed a proteomic-based triaging strategy using Reverse-phase Protein Arrays (RPPA) to optimize therapy selection. We evaluated the expression of 411 proteins in 810 newly diagnosed adult AML patients, identifying 109 prognostic proteins, that divided into five patient expression profiles, which are useful for optimizing therapy selection. Furthermore, …

Stat3 Protects Hematopoietic Stem Cells By Preventing Activation Of A Deleterious Autocrine Type-I Interferon Response, Bhakti Patel, Yifan Zhou, Rachel L Babcock, Feiyang Ma, M Anna Zal, Dhiraj Kumar, Yusra B Medik, Laura M Kahn, Josué E Pineda, Elizabeth M Park, Sarah M Schneider, Ximing Tang, Maria Gabriela Raso, Collene R Jeter, Tomasz Zal, Karen Clise-Dwyer, Khandan Keyomarsi, Filippo G Giancotti, Simona Colla, Stephanie S Watowich

Faculty, Staff and Student Publications

Hematopoietic stem and progenitor cells (HSPCs) maintain blood-forming and immune activity, yet intrinsic regulators of HSPCs remain elusive. STAT3 function in HSPCs has been difficult to dissect as Stat3-deficiency in the hematopoietic compartment induces systemic inflammation, which can impact HSPC activity. Here, we developed mixed bone marrow (BM) chimeric mice with inducible Stat3 deletion in 20% of the hematopoietic compartment to avoid systemic inflammation. Stat3-deficient HSPCs were significantly impaired in reconstitution ability following primary or secondary bone marrow transplantation, indicating hematopoietic stem cell (HSC) defects. Single-cell RNA sequencing of Lin-ckit+Sca1+ BM cells (LSKs) revealed aberrant activation of cell cycle, p53, …

Benefit Of Axicabtagene Ciloleucel Versus Chemoimmunotherapy In Older Patients And/Or Patients With Poor Ecog Performance Status With Relapsed Or Refractory Large B-Cell Lymphoma After 2 Or More Lines Of Prior Therapy, Matthew A Lunning, Hai-Lin Wang, Zhen-Huan Hu, Frederick L Locke, Tanya Siddiqi, Caron A Jacobson, Sairah Ahmed, David B Miklos, Yi Lin, Brian T Hill, Armin Ghobadi, Sattva S Neelapu, Jason Westin, Chrisopher Dieyi, Polly Field, Harry Miao, Shilpa A Shahani, Anik Patel, Clare Spooner, Christine Fu, David Muramoto, Hairong Xu, Marcelo C Pasquini

Faculty, Staff and Student Publications

Axicabtagene ciloleucel (axi-cel) in trials has demonstrated favorable efficacy compared with historical controls after ≥2 lines of therapy for the treatment of relapsed or refractory (R/R) large B cell lymphoma (LBCL). Herein, we compared the real-world effectiveness of axi-cel with efficacy and effectiveness of chemoimmunotherapy (CIT) in patients aged ≥65 years and patients with Eastern Cooperative Oncology Group performance status (ECOG PS) of 2. A total of 1146 patients treated with commercial axi-cel for R/R LBCL with ≥2 lines of prior therapy were included from the Center for International Blood and Marrow Transplantation Research prospective observational study, and 469 patients …

Does An Early, Balanced Resuscitation Strategy Reduce The Incidence Of Hypofibrinogenemia In Hemorrhagic Shock?, David T Lubkin, Krislynn M Mueck, Gabrielle E Hatton, Jason B Brill, Mariela Sandoval, Jessica C Cardenas, Charles E Wade, Bryan A Cotton

Faculty, Staff and Student Publications

OBJECTIVES: Some centers have recommended including concentrated fibrinogen replacement in massive transfusion protocols (MTPs). Given our center's policy of aggressive early balanced resuscitation (1:1:1), beginning prehospital, we hypothesized that our rates of hypofibrinogenemia may be lower than those previously reported.

METHODS: In this retrospective cohort study, patients presenting to our trauma center November 2017 to April 2021 were reviewed. Patients were defined as hypofibrinogenemic (HYPOFIB) if admission fibrinogen

RESULTS: Of 29 782 patients, 6618 level 1 activations, and 1948 patients receiving emergency release blood,

CONCLUSIONS: Low rates of hypofibrinogenemia were found in our center which treats hemorrhage with early, balanced …

Reduced Dose Azacitidine Plus Venetoclax As Maintenance Therapy In Acute Myeloid Leukaemia Following Intensive Or Low-Intensity Induction: A Single-Centre, Single-Arm, Phase 2 Trial, Alexandre Bazinet, Hagop Kantarjian, Alex Bataller, Naveen Pemmaraju, Gautam Borthakur, Kelly Chien, Yesid Alvarado, Prithviraj Bose, Elias Jabbour, Musa Yilmaz, Courtney Dinardo, Ghayas Issa, Guillermo Montalban-Bravo, Nicholas Short, Koji Sasaki, Debra Bull-Linderman, Naval Daver, Guillermo Garcia-Manero, Farhad Ravandi, Tapan Kadia

Faculty, Staff and Student Publications

Background: Patients with acute myeloid leukaemia have high rates of relapse, especially if they are unable to complete standard consolidation strategies or allogeneic haematopoietic stem-cell transplantation (HSCT). The phase 3 QUAZAR AML-001 study showed an overall survival benefit with oral azacitidine maintenance. The BCL2 inhibitor venetoclax is highly active in acute myeloid leukaemia and synergistic with azacitidine. We aimed to evaluate the efficacy and safety of low dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia.

Methods: We performed a single-centre, single-arm, phase 2 study at the University of Texas MD Anderson Cancer Center in the USA. Eligible …

Recurrent Nontraumatic Subgaleal Hematomas In A Pediatric Patient With Sickle Cell Disease, Irtiza N Sheikh, Olayinka Okeleji, Rabya Afzal, Eliana Bonfante, Monica Kodakandla, Neethu M Menon

Faculty, Staff and Student Publications

Spontaneous subgaleal hematoma in pediatric patients with sickle cell disease (SCD) is a rare occurrence that can present with symptoms mimicking ischemic stroke, a known complication of SCD. However, unlike ischemic stroke, subgaleal hematoma is nonlethal and can be managed conservatively without major sequelae. Here, we present the case of an adolescent with SCD who presented with 2 episodes of subgaleal and epidural hematomas, 2 years apart. The latter episode occurred while on crizanlizumab, an anti-P-selectin antibody, approved for use in SCD in 2019 to reduce the number of acute pain crises. We demonstrate the diagnosis of subgaleal hematoma and …

Dose-Dense Mini-Hyper-Cvd, Inotuzumab Ozogamicin And Blinatumomab Achieves Rapid Mrd-Negativity In Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia, Nicholas J Short, Elias Jabbour, Trevor Jamison, Shilpa Paul, Branko Cuglievan, David Mccall, Amber Gibson, Nitin Jain, Fadi G Haddad, Lewis F Nasr, Kayleigh R Marx, Caitlin Rausch, J Michael Savoy, Rebecca Garris, Farhad Ravandi, Hagop Kantarjian

Faculty, Staff and Student Publications

Background: The combination of low-intensity chemotherapy and inotuzumab ozogamicin (INO), with sequential blinatumomab, is highly effective in older adults with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) and in relapsed or refractory B-cell ALL. Earlier, "dose-dense" administration of blinatumomab could lead to earlier and deeper measurable residual disease (MRD) responses and better outcomes.

Patients and methods: We performed a retrospective analysis of the safety and efficacy of a dose-dense regimen of mini-hyper-CVD (mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with mini-methotrexate and cytarabine), INO, and blinatumomab in patients with B-cell ALL.

Results: Twenty-one patients were treated (frontline, n = 9; MRD …

Middle Meningeal Artery Embolization In Acute Leukemia Patients Presenting With Subdural Hematoma, Binoy Yohannan, Juan Carlos Martinez Gutierrez, Peng Roc Chen, Adan Rios

Faculty, Staff and Student Publications

Intracerebral hemorrhage is a potentially fatal complication in patients with acute leukemia and contributing factors include thrombocytopenia and coagulopathy. Patients with acute leukemia may develop subdural hematoma (SDH) spontaneously or secondary to trauma. In patients with acute leukemia and SDH, the surgical evacuation of the hematoma causes significant morbidity and mortality. New approaches and strategies to reduce the need for surgical evacuation are needed to improve outcomes in patients with acute leukemia and intracerebral hemorrhage. We report two cases of acute SDH in patients with acute leukemia successfully treated with middle meningeal artery embolization, a minimally invasive interventional radiology technique, …

Hematopoietic Stem Cells With Granulo-Monocytic Differentiation State Overcome Venetoclax Sensitivity In Patients With Myelodysplastic Syndromes, Juan Jose Rodriguez-Sevilla, Irene Ganan-Gomez, Feiyang Ma, Kelly Chien, Monica Del Rey, Sanam Loghavi, Guillermo Montalban-Bravo, Vera Adema, Bethany Wildeman, Rashmi Kanagal-Shamanna, Alexandre Bazinet, Helen T Chifotides, Natthakan Thongon, Xavier Calvo, Jesús María Hernández-Rivas, Maria Díez-Campelo, Guillermo Garcia-Manero, Simona Colla

Faculty, Staff and Student Publications

The molecular mechanisms of venetoclax-based therapy failure in patients with acute myeloid leukemia were recently clarified, but the mechanisms by which patients with myelodysplastic syndromes (MDS) acquire secondary resistance to venetoclax after an initial response remain to be elucidated. Here, we show an expansion of MDS hematopoietic stem cells (HSCs) with a granulo-monocytic-biased transcriptional differentiation state in MDS patients who initially responded to venetoclax but eventually relapsed. While MDS HSCs in an undifferentiated cellular state are sensitive to venetoclax treatment, differentiation towards a granulo-monocytic-biased transcriptional state, through the acquisition or expansion of clones with STAG2 or RUNX1 mutations, affects HSCs' …

Incidence And Risk Factors Of Early Onset Vod/Sos Differ In Younger Vs Older Adults After Stem Cell Transplantation, Curtis Marcoux, Rima M Saliba, Whitney Wallis, Sajad Khazal, Dristhi Ragoonanan, Gabriela Rondon, Priti Tewari, Uday Popat, Betul Oran, Amanda Olson, Qaiser Bashir, Muzaffar Qazilbash, Amin Alousi, Chitra Hosing, Yago Nieto, Gheath Alatrash, David Marin, Katayoun Rezvani, Issa Khouri, Samer Srour, Richard Champlin, Elizabeth Shpall, Partow Kebriaei

Faculty, Staff and Student Publications

Veno-occlusive disease (VOD) is a rare but potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Although increasing awareness and modern transplant techniques have mitigated risk, the interaction of historic risk factors in the current era with posttransplant cyclophosphamide (PTCy) is unknown. We performed a retrospective single-center analysis of adult patients aged ≥18 years undergoing allo-SCT (N = 1561) using predominately PTCy as graft-versus-host disease (GVHD) prophylaxis (72%). We found a higher rate of VOD at 16.8% (20 of 119) in those aged ≤25 years compared with 3.8% (55 of 1442) in those aged >25 years, with unique predictors …

The Lymphoma Epidemiology Of Outcomes Cohort Study: Design, Baseline Characteristics, And Early Outcomes, James R Cerhan, Matthew J Maurer, Brian K Link, Andrew L Feldman, Thomas M Habermann, David L Jaye, W Richard Burack, Timothy J Mcdonnell, Francisco Vega, Jennifer R Chapman, Sergei Syrbu, Kiran R Vij, Giorgio Inghirami, John P Leonard, Leon Bernal-Mizrachi, Umar Farooq, Thomas E Witzig, George J Weiner, Yucai Wang, Juan P Alderuccio, Susan L Slager, Melissa C Larson, Shaun M Riska, Brianna J Gysbers, Julianne J Lunde, Tanner W Reicks, Amy A Ayers, Colin B O'Leary, Kathleen J Yost, Hongfang Liu, Grzegorz S Nowakowski, Jia Ruan, Dai Chihara, Jean L Koff, Carla Casulo, Carrie A Thompson, Jonathon B Cohen, Brad S Kahl, Loretta J Nastoupil, Izidore S Lossos, Jonathan W Friedberg, Peter Martin, Christopher R Flowers

Faculty, Staff and Student Publications

To address the current and long-term unmet health needs of the growing population of non-Hodgkin lymphoma (NHL) patients, we established the Lymphoma Epidemiology of Outcomes (LEO) cohort study (NCT02736357; https://leocohort.org/). A total of 7735 newly diagnosed patients aged 18 years and older with NHL were prospectively enrolled from 7/1/2015 to 5/31/2020 at 8 academic centers in the United States. The median age at diagnosis was 62 years (range, 18-99). Participants came from 49 US states and included 538 Black/African-Americans (AA), 822 Hispanics (regardless of race), 3386 women, 716 age <40 >years, and 1513 rural residents. At study baseline, we abstracted clinical, …

Safety, Efficacy And Determinants Of Response Of Allogeneic Cd19-Specific Car-Nk Cells In Cd19+ B Cell Tumors: A Phase 1/2 Trial, David Marin, Ye Li, Rafet Basar, Hind Rafei, May Daher, Jinzhuang Dou, Vakul Mohanty, Merve Dede, Yago Nieto, Nadima Uprety, Sunil Acharya, Enli Liu, Jeffrey Wilson, Pinaki Banerjee, Homer A Macapinlac, Christina Ganesh, Peter F Thall, Roland Bassett, Mariam Ammari, Sheetal Rao, Kai Cao, Mayra Shanley, Mecit Kaplan, Chitra Hosing, Partow Kebriaei, Loretta J Nastoupil, Christopher R Flowers, Sadie Mae Moseley, Paul Lin, Sonny Ang, Uday R Popat, Muzaffar H Qazilbash, Richard E Champlin, Ken Chen, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted a phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 chimeric antigen receptor and interleukin-15 (CAR19/IL-15) in 37 patients with CD19+ B cell malignancies. The primary objectives were safety and efficacy, defined as day 30 overall response (OR). Secondary objectives included day 100 response, progression-free survival, overall survival and CAR19/IL-15 NK cell persistence. No notable toxicities such as cytokine release syndrome, neurotoxicity or graft-versus-host disease were observed. The day 30 and day 100 OR rates were …

Impact Of Electronic Cigarettes On Pediatric, Adolescent And Young Adult Leukemia Patients, Sanila Sarkar, Lea M Stitzlein, Joya Chandra

Faculty, Staff and Student Publications

Electronic cigarettes, which deliver an aerosolized, nicotine-containing product upon inhalation, are a public health issue that continue to gain popularity among adolescents and young adults in the United States. Use of electronic cigarettes is wide, and extends to pediatric patients with multiple comorbidities, including childhood cancer, leaving them vulnerable to further negative health outcomes. Acute leukemias are the most common type of cancer in pediatric populations, and treatment outcomes for these patients are improving; consequently, there is an increased emphasis on the effect of behavioral lifestyle factors on quality of life in survivorship. The rate of electronic cigarette use is …

Gamma Delta T Cells In Acute Myeloid Leukemia: Biology And Emerging Therapeutic Strategies, Adishwar Rao, Akriti Agrawal, Gautam Borthakur, Venkata Lokesh Battula, Abhishek Maiti

Faculty, Staff and Student Publications

γδ T cells play an important role in disease control in acute myeloid leukemia (AML) and have become an emerging area of therapeutic interest. These cells represent a minor population of T lymphocytes with intrinsic abilities to recognize antigens in a major histocompatibility complex-independent manner and functionally straddle the innate and adaptive immunity interface. AML shows high expression of phosphoantigens and UL-16 binding proteins that activate the Vδ2 and Vδ1 subtypes of γδ T cells, respectively, leading to γδ T cell-mediated cytotoxicity. Insights from murine models and clinical data in humans show improved overall survival, leukemia-free survival, reduced risk of …

A Phase 1/2 Study Of Mini-Hyper-Cvd Plus Venetoclax In Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia, Nicholas J Short, Elias Jabbour, Nitin Jain, Jayastu Senapati, Lewis Nasr, Fadi G Haddad, Zhenhua Li, Yu-Chih Hsiao, Jun J Yang, Naveen Pemmaraju, Maro Ohanian, William G Wierda, Guillermo Montalban-Bravo, Gautam Borthakur, Lina Han, Lianchun Xiao, Xuelin Huang, Regina Abramova, Min Zhao, Rebecca Garris, Marina Konopleva, Farhad Ravandi, Hagop Kantarjian

Faculty, Staff and Student Publications

Preclinical studies suggest that Bcl-2 inhibition with venetoclax has antileukemic activity in acute lymphoblastic leukemia (ALL) and may synergize with conventional chemotherapy. We designed a phase 1/2 clinical trial to evaluate the safety and efficacy of low-intensity chemotherapy in combination with venetoclax in adults with relapsed or refractory ALL. Patients received the mini-hyper-CVD regimen (dose-attenuated hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with methotrexate and cytarabine) in combination with venetoclax (200 mg or 400 mg daily) on days 1 to 14 in cycle 1 and on days 1 to 7 in consolidation cycles. Twenty-two patients were treated. The median number of …

Cerebral Oxygenation Monitoring For Early Detection Of Subarachnoid Haemorrhage In Infratentorial Arteriovenous Malformation Undergoing Embolisation: A Case Study, Kunal K Sharma, Prachi Sharma, Rohini M Surve

Faculty, Staff and Student Publications

No abstract provided.

From Primary Myelofibrosis To Chronic Myeloid Leukemia, Bcr::Abl1+ B-Lymphoblastic Leukemia, And Back To Primary Myelofibrosis: An Illustration Of Dynamic Clonal Evolution, Devin Wang, Wataru Kamata, Fengxi Ye, M James You

Faculty, Staff and Student Publications

The simultaneous detection of BCR::ABL1 and JAK2 V617F was rarely reported and their clonal relationship and dynamic clonal shift were not characterized. Here, we described a unique case with the initial presentation as JAK2 V617F+ primary myelofibrosis, followed by the emergence of BCR::ABL1+ chronic myeloid leukemia. The patient then developed BCR::ABL1+ B-lymphoblastic leukemia. Treatment for B-lymphoblastic leukemia prompted a regression to the state of primary myelofibrosis. In light of these observations, we proposed a clonal evolution model for this case.

Safety And Efficacy Of A New High-Dose Regimen Of Panobinostat, Gemcitabine, Busulfan, And Melphalan For 1st Or 2nd Salvage Asct For Refractory/Relapsed Or High-Risk Myeloma: Matched-Pair Comparisons With Concurrent Control Cohorts, Yago Nieto, Zixi Yang, Benigno C Valdez, Suprateek Kundu, Qaiser Bashir, Jeremy Ramdial, Samer Srour, Muzaffar Qazilbash

Faculty, Staff and Student Publications

Improvement of autologous stem-cell transplantation (ASCT) for myeloma is needed. Building on our prior work, we prospectively evaluated panobinostat and gemcitabine/busulfan/melphalan (GemBuMel) with ASCT in this population. Patients aged 18-65 years with relapsed/refractory or high-risk myeloma and adequate end-organ function were eligible. Treatment included panobinostat (20 mg/day, days -9 to -2) and GemBuMel (days -8 to -2). Patients were enrolled in 1st (ASCT-1) or 2nd ASCT (ASCT-2) cohorts. We compared their outcomes with all our other concurrent ASCT patients who met eligibility criteria but received melphalan or BuMel off study, matched for age, prior therapy lines, high-risk cytogenetics, and response …

Incidence And Predictors Of Post-Thrombotic Syndrome In Patients With Proximal Dvt In A Real-World Setting: Findings From The Garfield-Vte Registry, Paolo Prandoni, Sylvia Haas, Meg E Fluharty, Sebastian Schellong, Harry Gibbs, Eric Tse, Marc Carrier, Barry Jacobson, Hugo Ten Cate, Elizaveta Panchenko, Peter Verhamme, Karen Pieper, Gloria Kayani, Lord A Kakkar

Faculty, Staff and Student Publications

Although substantial progress has been made in the pathophysiology and management of the post-thrombotic syndrome (PTS), several aspects still need clarification. Among them, the incidence and severity of PTS in the real world, the risk factors for its development, the value of patient's self-evaluation, and the ability to identify patients at risk for severe PTS. Eligible participants (n = 1107) with proximal deep-vein thrombosis (DVT) from the global GARFIELD-VTE registry underwent conventional physician's evaluation for PTS 36 months after diagnosis of their DVT using the Villalta score. In addition, 856 patients completed a Villalta questionnaire at 24 months. Variable selection …