Hemic and Lymphatic Diseases Commons^™

Optimizing Electrode Placement And Information Capacity For Local Field Potentials In Cortex, Jace A Willis, Christopher E Wright, Ruoqian Zhu, Yilan Ruan, Joshua Stallings, Amada M Abrego, Takfarinas Medani, Promit Moitra, Arjun Ramakrishnan, Charles E Schroeder, Anand A Joshi, Nitin Tandon, Richard M Leahy, John C Mosher, John P Seymour

Faculty, Staff and Student Publications

Recent neurosurgery advancements include improved stereotactic targeting and increased density and specificity of electrophysiological evaluation. This study introduces a subject-specific, in silico modeling tool for optimizing electrode placement and maximizing coverage with a variety of devices. The basis for optimization is the Shannon-Hartley information capacity of field potentials derived from dipolar sources. The approach integrates subject-specific MRI data with finite element modeling (FEM) used to simulate the sensitivity of subdural and intracortical devices. Sensitivity maps, or lead fields, from these models enable the comparison of different electrode placements, contact sizes, contact configurations, and substrate properties, which are often overlooked factors. …

The Immunophenotypic And Genetic Characterization Of Pediatric T -L Ymphoblastic Leukemia With A Mature Immunophenotype, Mahsa Khanlari, Wei Wang, Parastou Tizro, Mohammad K Eldomery

Faculty, Staff and Student Publications

Not available.

Ptpn11 Mutations Define A Rare But Highly Adverse Subset Of Myelodysplastic Syndromes, Alexandre Bazinet, Alex Bataller, Guillermo Montalban-Bravo, Kelly Chien, Koji Sasaki, Wei Ying Jen, Mahesh Swaminathan, Tapan Kadia, Courtney Dinardo, Farhad Ravandi, Guillermo Garcia-Manero, Hagop Kantarjian

Faculty, Staff and Student Publications

No abstract provided.

Risk Of Early Death After Acute Leukemia Diagnosis Among Adolescents And Young Adults, Amy M Berkman, Clark R Andersen, Vidya Puthenpura, Nicholas J Short, Kelly Merriman, Mahesh Swaminathan, Branko Cuglievan, David Mccall, Courtney Dinardo, Cesar Nunez, Nitin Jain, Tapan Kadia, Ghayas Issa, Amber Gibson, Miriam B Garcia, J Andrew Livingston, Susan Parsons, Michelle A T Hildebrandt, Michael E Roth

Faculty, Staff and Student Publications

Background: Advances in care have led to improvements in survival for adolescents and young adults (AYAs) diagnosed with cancer; however, the risk of early death remains high for certain cancers, particularly acute leukemias. Risk factors for early death in AYAs diagnosed with acute leukemia have not been well studied.

Methods: The Surveillance, Epidemiology, and End Results registry was used to assess risk of early death (within 2 months of diagnosis) in AYAs diagnosed with acute leukemia (n = 16 153). Early death proportion, by year, for AYAs diagnosed between 2006 and 2020 was described. Associations between incidence of early death …

A Phase Ii Trial Of Azacitidine With Ipilimumab, Nivolumab, Or Ipilimumab And Nivolumab In Previously Untreated Myelodysplastic Syndrome, Ian M Bouligny, Guillermo Montalban-Bravo, Koji Sasaki, Naval Daver, Elias Jabbour, Yesid Alvarado, Courtney D Dinardo, Farhad Ravandi, Gautam Borthakur, Prithviraj Bose, Naveen Pemmaraju, Steven Kornblau, Tapan Kadia, Lucia Masarova, Koichi Takahashi, Michael Andreeff, Alexandre Bazinet, Hui Yang, Rashmi Kanagal-Shamanna, Chitra Hosing, Sherry Pierce, Meghan Meyer, Xuelin Huang, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

No abstract provided.

Clinical Interrogation Of Tp53 Aberrations And Its Impact On Survival In Patients With Myeloid Neoplasms, Jayastu Senapati, Sanam Loghavi, Guillermo Garcia-Manero, Guillin Tang, Tapan Kadia, Nicholas J Short, Hussein A Abbas, Naszrin Arani, Courtney D Dinardo, Gautam Borthakur, Naveen Pemmaraju, Betul Oran, Elizabeth Shpall, Uday Popat, Richard Champlin, Sherry Pierce, Sankalp Arora, Ghayas Issa, Musa Yilmaz, Keyur Patel, Koichi Takahashi, Guillermo Montalban-Bravo, Danielle Hammond, Fadi G Haddad, Farhad Ravandi, Hagop M Kantarjian, Naval G Daver

Faculty, Staff and Student Publications

In myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with TP53 aberrations, dissecting the interaction amongst patient, disease and treatment factors are important for therapeutic decisions and prognostication. This retrospective analysis included patients with newly diagnosed MDS (>5% blasts) and AML with TP53 mutation(s) treated at MD Anderson Cancer Center. We factored patient age, TP53 aberration burden, therapy intensity and use of venetoclax in the AML subgroup, and allogeneic hematopoietic stem cell transplantation (HSCT) to interrogate outcomes. TP53 was annotated as high-risk (TP53HR) if >1 mutation, one mutation plus allelic deletion or a single mutation with variant allele frequency …

Prospective Clinical Trials Of Venetoclax And Hypomethylating Agents For Relapsed Bpdcn, Naveen Pemmaraju, Luan Hai Phan, Geoffrey Fell, Marlise R Luskin, Mahesh Swaminathan, Sherry Pierce, Courtney Dinardo, Abhishek Maiti, Marina Konopleva, Andrew A Lane

Faculty, Staff and Student Publications

No abstract provided.

Long Term Results Of Venetoclax Combined With Flag-Ida Induction And Consolidation For Newly Diagnosed And Relapsed Or Refractory Acute Myeloid Leukemia, Courtney D Dinardo, Wei-Ying Jen, Koichi Takahashi, Tapan M Kadia, Sanam Loghavi, Naval G Daver, Lianchun Xiao, Patrick K Reville, Ghayas C Issa, Nicholas J Short, Koji Sasaki, Sa A Wang, Jillian K Mullin, Sherry Pierce, Corey Bradley, Gautam Borthakur, Abhishek Maiti, Yesid Alvarado, Naveen Pemmaraju, Alessandra Ferrajoli, Mahesh Swaminathan, Maro Ohanian, Hussein A Abbas, Danielle Hammond, Jan Burger, Fadi Haddad, Guillermo Montalban-Bravo, Kelly Chien, Lucia Masarova, Musa Yilmaz, Nitin Jain, Michael Andreeff, Guillermo Garcia-Manero, Steven Kornblau, Farhad Ravandi, Elias Jabbour, Marina Y Konopleva, Hagop M Kantarjian

Faculty, Staff and Student Publications

Intensive chemotherapy remains the standard for newly diagnosed (ND) acute myeloid leukemia (AML); however, relapse risk remains high. Additionally, most patients with relapsed/refractory (RR) AML have poor outcomes. We report the long-term experience of 138 patients, 77 ND and 61 RR, treated with FLAG-IDA in combination with venetoclax. In the ND cohort, the overall response rate (ORR) was 97%, with a composite complete remission (CRc) rate of 95% and undetectable measurable residual disease (MRD) status by flow cytometry in 90%. The 3-year OS and EFS rates were 66 and 64%, respectively. Outcomes were similar across European LeukemiaNet (ELN) 2022 risk …

Oral Decitabine Cedazuridine With And Without Venetoclax In Higher-Risk Myelodysplastic Syndromes Or Chronic Myelomonocytic Leukemia: A Propensity Score-Matched Study, Alex Bataller, Koji Sasaki, Samuel Urrutia, Guillermo Montalban-Bravo, Alexandre Bazinet, Kelly Chien, Danielle Hammond, Ian M Bouligny, Mahesh Swaminathan, Ghayas Issa, Nicholas Short, Naval Daver, Courtney D Dinardo, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gail J Roboz, Michael Savona, Elizabeth A Griffiths, James Mccloskey, Olatoyosi Odenike, Aram Oganesian, Harold N Keer, Mohammad Azab, Hagop Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Hypomethylating agents (HMA) are indicated in the treatment of higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The combination of hypomethylating agents with venetoclax (Ven) has demonstrated promising results in these diseases, although randomized clinical trials are needed for validation. In this retrospective study, we compared two matched cohorts of patients with MDS or CMML: one receiving oral decitabine-cedazuridine (DEC-C, n = 73) and one receiving DEC-C and Ven (DEC-C-Ven, n = 51), in three contemporary clinical trials. The aim is to determine the impact of the addition of Ven to HMA in MDS and CMML. Individuals were matched …

Cryptic Kmt2a::Afdn Fusion Due To Afdn Insertion Into Kmt2a In A Patient With Acute Monoblastic Leukemia, Qing Wei, Gokce A Toruner, Beenu Thakral, Keyur P Patel, Naveen Pemmaraju, Sa A Wang, Rashmi Kanagal-Shamanna, Guilin Tang, Ghayas C Issa, Sanam Loghavi, L Jeffrey Medeiros, Courtney Dinardo

Faculty, Staff and Student Publications

Background: KMT2A rearrangements occur in ~10% of acute myeloid leukemia (AML) cases and are critical for classification, risk stratification, and use of targeted therapy. However, insertions involving the KMT2A gene can evade detection using chromosomal analysis and/or fluorescence in situ hybridization (FISH).

Methods: We present a case of a 22-year-old woman with acute monoblastic leukemia harboring a cryptic KMT2A::AFDN fusion identified by RNA sequencing. Initial FISH showed a 3' KMT2A deletion, while conventional karyotyping and the automated bioinformatic pipeline for optical genome mapping (OGM) did not identify the canonical translocation.

Results: To resolve these discrepancies, metaphase KMT2A FISH (break-apart fusion …

Management Of Hemolytic Transfusion Reactions In A Patient With Chronic Myelomonocytic Leukemia And Rare Antibodies: A Case Report, Grace S Park, Himachandana Atluri, Courtney D Dinardo, Bryan Guillroy, Jean Horak, Effrosyni Apostolidou, Maryam Buni, Guillermo Montalban Bravo, Naveen Pemmaraju

Faculty, Staff and Student Publications

Delayed hemolytic transfusion reaction (DHTR) poses a significant challenge in patients receiving blood transfusions. This case report highlights the complexities of managing DHTR in a newly diagnosed chronic myelomonocytic leukemia (CMML) patient with clinically significant JKa and little c antibodies during induction chemotherapy. A 46-year-old woman with CMML-2 who presented for induction chemotherapy was found to have hemolytic anemia. Due to presence of JKa and little c antibodies, she required intensive monitoring and supportive care measures. The coexistence of JKa and little c antibodies complicates transfusion management and chemotherapy tolerance in CMML patients.

The Impact Of Post-Remission Granulocyte Colony-Stimulating Factor Use In The Phase 3 Studies Of Venetoclax Combination Treatments In Patients With Newly Diagnosed Acute Myeloid Leukemia, Courtney D Dinardo, Keith W Pratz, Panayiotis Panayiotidis, Xudong Wei, Vladimir Vorobyev, Árpád Illés, Inho Kim, Vladimir Ivanov, Grace Ku, Catherine L Miller, Meng Zhang, Fernando Tatsch, Jalaja Potluri, Xenia Schmidt, Christian Récher

Faculty, Staff and Student Publications

No abstract provided.

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Alexander M Xu, Dylan Jochum, Issa Ismail Issa, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

Lp-118 Is A Novel B-Cell Lymphoma 2 / Extra-Large Inhibitor That Demonstrates Efficacy In Models Of Venetoclaxresistant Chronic Lymphocytic Leukemia, Janani Ravikrishnan, Daisy Y Diaz-Rohena, Elizabeth Muhowski, Xiaokui Mo, Tzung-Huei Lai, Shrilekha Misra, Charmelle D Williams, John Sanchez, Andrew Mitchell, Suresh Satpati, Elizabeth Perry, Tierney Kaufman, Chaomei Liu, Arletta Lozanski, Gerard Lozanski, Kerrya Rogers, Adam S Kittai, Seema A Bhat, Mary C Collins, Matthew S Davids, Nitin Jain, William G Wierda, Rosa Lapalombella, John C Byrd, Fenlai Tan, Yi Chen, Yu Chen, Yue Shen, Stephen P Anthony, Jennifer A Woyach, Deepa Sampath

Faculty, Staff and Student Publications

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis …

Deep Dive Into Targeted Therapies: Understanding Idh1-Mutant Aml Treatments [Podcast], Amer M Zeidan, Courtney Dinardo

Faculty, Staff and Student Publications

This podcast episode reviews recent advances in the treatment of IDH1-mutant acute myeloid leukemia (AML), focusing on the mechanisms, efficacy, and safety profiles of approved IDH1 inhibitors. The purpose is to present expert insights and clinical data from key trials that underscore the clinical benefits of these targeted therapies. Through discussion of key findings from pivotal clinical trial studies, including data supporting the use of these agents in both newly diagnosed and relapsed or refractory (R/R) settings, the episode highlights significant outcomes such as increased overall response and prolonged duration of remission in patients treated with IDH1 inhibitors. The analysis …

Mutation- And Mrd-Informed Treatments For Transplant-Ineligible Patients, Curtis A Lachowiez, Courtney D Dinardo

Faculty, Staff and Student Publications

The ongoing development of molecularly targeted therapies in addition to the new standard of care combination of azacitidine and venetoclax (AZA-VEN) has transformed the prognostic outlook for older, transplant-ineligible patients with acute myeloid leukemia (AML). While conventional treatments, such as standard anthracycline and cytarabine- based chemotherapy or hypomethylating agent (HMA) monotherapy, are associated with a generally poor prognosis in this patient population, the use of these novel regimens can result in long-lasting, durable remissions in select patient subgroups. Furthermore, the simultaneous discovery of resistance mechanisms to targeted therapies and AZA-VEN has enabled the identification of patient subgroups with inferior outcomes, …

Genetically Determined Telomere Length In Monoclonal Gammopathy Of Undetermined Significance, Multiple Myeloma Risk And Outcome, Matteo Giaccherini, Alyssa I Clay-Gilmour, Romano Liotti, Angelica Macauda, Manuel Gentiluomo, Elizabeth E Brown, Mitchell J Machiela, Stephen J Chanock, Michelle A T Hildebrandt, Aaron D Norman, Elisabet Manasanch, S Vincent Rajkumar, Jonathan N Hofmann, Sonja I Berndt, Parveen Bhatti, Graham G Giles, Elad Ziv, Shaji K Kumar, Nicola J Camp, Wendy Cozen, Susan L Slager, Federico Canzian, Federica Gemignani, Celine M Vachon, Daniele Campa

Faculty, Staff and Student Publications

No abstract provided.

Outcomes And Genetic Dynamics Of Acute Myeloid Leukemia At First Relapse, Alex Bataller, Hagop Kantarjian, Alexandre Bazinet, Tapan Kadia, Naval Daver, Courtney D Dinardo, Gautam Borthakur, Sanam Loghavi, Keyur Patel, Guilin Tang, Koji Sasaki, Nicholas J Short, Musa Yilmaz, Ghayas C Issa, Yesid Alvarado, Guillermo Montalban-Bravo, Abhishek Maiti, Hussein A Abbas, Koichi Takahashi, Sherry Pierce, Elias Jabbour, Guillermo Garcia-Manero, Farhad Ravandi

Faculty, Staff and Student Publications

Patients with relapsed acute myeloid leukemia (AML) experience dismal outcomes. We performed a comprehensive analysis of patients with relapsed AML to determine the genetic dynamics and factors predicting survival. We analyzed 875 patients with newly diagnosed AML who received intensive treatment or low-intensity treatment. Of these patients, 197 subsequently relapsed. Data were available for 164 of these patients, with a median time from complete remission/complete remission with incomplete blood count recovery to relapse of 6.5 months. Thirty-five of the 164 patients (21%) experienced relapse after allogeneic hematopoietic stem cell transplantation. At relapse, mutations in genes involved in pathway signaling tended …

The Dleu2/Mir-15a/Mir-16-1 Cluster Shapes The Immune Microenvironment Of Chronic Lymphocytic Leukemia, Ronghua Zhang, Priyanka Khare, Priyanka Banerjee, Cristina Ivan, Sarah Schneider, Federica Barbaglio, Karen Clise-Dwyer, Vanessa Behrana Jensen, Erika Thompson, Marisela Mendoza, Nicholas Chiorazzi, Shih-Shih Chen, Xiao-Jie Joy Yan, Nitin Jain, Paolo Ghia, Federico Caligaris-Cappio, Rima Mendonsa, Sashi Kasimsetty, Ryan Swoboda, Recep Bayraktar, William Wierda, Varsha Gandhi, George A Calin, Michael J Keating, Maria Teresa Sabrina Bertilaccio

Faculty, Staff and Student Publications

The development and progression of chronic lymphocytic leukemia (CLL) depend on genetic abnormalities and on the immunosuppressive microenvironment. We have explored the possibility that genetic drivers might be responsible for the immune cell dysregulation that shapes the protumor microenvironment. We performed a transcriptome analysis of coding and non-coding RNAs (ncRNAs) during leukemia progression in the Rag2-/-γc-/- MEC1-based xenotransplantation model. The DLEU2/miR-16 locus was found downmodulated in monocytes/macrophages of leukemic mice. To validate the role of this cluster in the tumor immune microenvironment, we generated a mouse model that simultaneously mimics the overexpression of hTCL1 and the germline deletion of the …

Menin Inhibitors In Pediatric Acute Leukemia: A Comprehensive Review And Recommendations To Accelerate Progress In Collaboration With Adult Leukemia And The International Community, Branko Cuglievan, Hagop Kantarjian, Jeffrey E Rubnitz, Todd M Cooper, C Michel Zwaan, Jessica A Pollard, Courtney D Dinardo, Tapan M Kadia, Erin Guest, Nicholas J Short, David Mccall, Naval Daver, Cesar Nunez, Fadi G Haddad, Miriam Garcia, Kapil N Bhalla, Abhishek Maiti, Samanta Catueno, Warren Fiskus, Bing Z Carter, Amber Gibson, Michael Roth, Sajad Khazal, Priti Tewari, Hussein A Abbas, Wallace Bourgeois, Michael Andreeff, Neerav N Shukla, Danh D Truong, Jeremy Connors, Joseph A Ludwig, Janine Stutterheim, Elisabeth Salzer, Kristian L Juul-Dam, Koji Sasaki, Kris M Mahadeo, Sarah K Tasian, Gautam Borthakur, Samantha Dickson, Nitin Jain, Elias Jabbour, Soheil Meshinchi, Guillermo Garcia-Manero, Farhad Ravandi, Eytan M Stein, E Anders Kolb, Ghayas C Issa

Faculty, Staff and Student Publications

Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell …

Personalized Neoantigen Vaccines As Early Intervention In Untreated Patients With Lymphoplasmacytic Lymphoma: A Non-Randomized Phase 1 Trial, Szymon J Szymura, Lin Wang, Tiantian Zhang, Soung-Chul Cha, Joo Song, Zhenyuan Dong, Aaron Anderson, Elizabeth Oh, Vincent Lee, Zhe Wang, Sapna Parshottam, Sheetal Rao, Jasper B Olsem, Brandon N Crumpton, Hans C Lee, Elisabet E Manasanch, Sattva Neelapu, Larry W Kwak, Sheeba K Thomas

Faculty, Staff and Student Publications

Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. …

Sotatercept For Anemia Of Myelofibrosis: A Phase Ii Investigator-Initiated Study, Prithviraj Bose, Lucia Masarova, Naveen Pemmaraju, Sharon D Bledsoe, Naval G Daver, Elias J Jabbour, Tapan M Kadia, Zeev Estrov, Steven M Kornblau, Michael Andreeff, Nitin Jain, Jorge E Cortes, Gautam Borthakur, Yesid Alvarado, Mary Ann Richie, Mackenzie H Dobbins, Selene A Mccrackin, Lingsha Zhou, Sherry A Pierce, Xuemei Wang, Allison M Pike, Guillermo Garcia-Manero, Hagop M Kantarjian, Srdan Verstovsek

Faculty, Staff and Student Publications

No abstract provided.

Acute Myeloid Leukemia With Mast Cell Differentiation Is Characterized By Interstitial Mast Cells, Complex Karyotype, Do Hwan Kim, Sa A Wang, Wei Wang, Guilin Tang, Shaoying Li, C Cameron Yin, Pei Lin, Marina Konopleva, M James You, Roberto N Miranda, Xiaoqiong Wang, Qing Wei, L Jeffrey Medeiros, Jie Xu

Faculty, Staff and Student Publications

No abstract provided.

Impact Of Patient Demographics And Neighborhood Socioeconomic Variables On Clinical Trial Participation Patterns For Nhl, Chijioke Nze, Clark R Andersen, Amy A Ayers, Jason Westin, Michael Wang, Swaminathan Iyer, Sairah Ahmed, Chelsea Pinnix, Francisco Vega, Lynne Nguyen, Lorna Mcneill, Loretta J Nastoupil, Kehe Zhang, Cici X Bauer, Christopher R Flowers

Faculty, Staff and Student Publications

Prior studies have demonstrated that certain populations including older patients, racial/ethnic minority groups, and women are underrepresented in clinical trials. We performed a retrospective analysis of patients with non-Hodgkin lymphoma (NHL) seen at MD Anderson Cancer Center (MDACC) to investigate the association between trial participation, race/ethnicity, travel distance, and neighborhood socioeconomic status (nSES). Using patient addresses, we ascertained nSES variables on educational attainment, income, poverty, racial composition, and housing at the census tract (CT) level. We also performed geospatial analysis to determine the geographic distribution of clinical trial participants and distance from patient residence to MDACC. We examined 3146 consecutive …

Chronic Eosinophilic Leukemia With A Novel Jak1 Mutation Responds Well To The Jak1/2 Inhibitor Ruxolitinib, Qing Wei, Jie Xu

Faculty, Staff and Student Publications

No abstract provided.

Daratumumab In Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma: Final Analysis Of Clinically Relevant Subgroups In Griffin, Ajai Chari, Jonathan L Kaufman, Jacob Laubach, Douglas W Sborov, Brandi Reeves, Cesar Rodriguez, Rebecca Silbermann, Luciano J Costa, Larry D Anderson, Nitya Nathwani, Nina Shah, Naresh Bumma, Sarah A Holstein, Caitlin Costello, Andrzej Jakubowiak, Tanya M Wildes, Robert Z Orlowski, Kenneth H Shain, Andrew J Cowan, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S Lin, Peter M Voorhees, Saad Z Usmani, Paul G Richardson

Faculty, Staff and Student Publications

The randomized, phase 2 GRIFFIN study (NCT02874742) evaluated daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM). We present final post hoc analyses (median follow-up, 49.6 months) of clinically relevant subgroups, including patients with high-risk cytogenetic abnormalities (HRCAs) per revised definition (del[17p], t[4;14], t[14;16], t[14;20], and/or gain/amp[1q21]). Patients received 4 induction cycles (D-RVd/RVd), high-dose therapy/transplant, 2 consolidation cycles (D-RVd/RVd), and lenalidomide±daratumumab maintenance (≤ 2 years). Minimal residual disease–negativity (10−5) rates were higher for D-RVd versus RVd in patients ≥ 65 years (67.9% vs 17.9%), with HRCAs (54.8% vs 32.4%), and with gain/amp(1q21) (61.8% vs 28.6%). D-RVd showed a …

Luspatercept Enhances Hemoglobin Levels In A Chinese Boy With Congenital Sideroblastic Anemia: A Case Report, Yuan Li, Lei Ye, Kang Zhou, Hui-Hui Fan, Jian-Ping Li, You-Zhen Xiong, Yang Yang, Guang-Xin Peng, Wen-Rui Yang, Xin Zhao, Li-Ping Jing, Li Zhang, Feng-Kui Zhang

Faculty, Staff and Student Publications

BACKGROUND: Congenital sideroblastic anemia (CSA) is a rare and heterogeneous group of genetic disorders. Conventional treatment include pyridoxine (vitamin B6) and allogeneic hematopoietic stem cell transplantation (allo-HSCT), and can alleviate anemia in the majority of cases. Nevertheless, some CSA cases remain unresponsive to pyridoxine or are unable to undergo allo-HSCT. Novel management approaches is necessary to be developed. To explore the response of luspatercept in treating congenital sideroblastic anemia.

CASE SUMMARY: We share our experience in luspatercept in a 4-year-old male patient with CSA. Luspatercept was administered subcutaneously at doses of 1.0 mg/kg/dose to 1.25 mg/kg/dose every 3 wk, three …

Hairy Cell Leukemia Variant And Who Classification Correspondence Re: 5th Edition Who Classification Haematolymphoid Tumors: Lymphoid Neoplasms, Michael Grever, Leslie Andritsos, Mirela Anghelina, Evgeny Arons, Versha Banerji, Jacqueline Barrientos, Seema A Bhat, James Blachly, Alessandro Broccoli, Timothy Call, Claire Dearden, Sascha Dietrich, Monica Else, Narendranath Epperla, Andrei Fagarasanu, Brunangelo Falini, Francesco Forconi, Alessandro Gozzetti, Paul Hampel, David J Hermel, Sunil Iyengar, James B Johnston, Gunnar Juliusson, Robert J Kreitman, Francesco Lauria, Gerard Lozanski, Christopher C Oakes, Sameer A Parikh, Jae Park, Graeme Quest, Kanti Rai, Farhad Ravandi, Tadeusz Robak, Kerry A Rogers, Alan Saven, John F Seymour, Tamar Tadmor, Martin S Tallman, Constantine S Tam, Enrico Tiacci, Xavier Troussard, Bernhard Wörmann, Clive S Zent, Thorsten Zenz, Pier Luigi Zinzani

Faculty, Staff and Student Publications

No abstract provided.

Plasmacytoid Dendritic Cells Control Homeostasis Of Megakaryopoiesis, Florian Gaertner, Hellen Ishikawa-Ankerhold, Susanne Stutte, Wenwen Fu, Jutta Weitz, Anne Dueck, Bhavishya Nelakuditi, Valeria Fumagalli, Dominic Van Den Heuvel, Larissa Belz, Gulnoza Sobirova, Zhe Zhang, Anna Titova, Alejandro Martinez Navarro, Kami Pekayvaz, Michael Lorenz, Louisa Von Baumgarten, Jan Kranich, Tobias Straub, Bastian Popper, Vanessa Zheden, Walter Anton Kaufmann, Chenglong Guo, Guido Piontek, Saskia Von Stillfried, Peter Boor, Marco Colonna, Sebastian Clauß, Christian Schulz, Thomas Brocker, Barbara Walzog, Christoph Scheiermann, William C Aird, Claus Nerlov, Konstantin Stark, Tobias Petzold, Stefan Engelhardt, Michael Sixt, Robert Hauschild, Martina Rudelius, Robert A J Oostendorp, Matteo Iannacone, Matthias Heinig, Steffen Massberg

Faculty, Staff and Student Publications

Platelet homeostasis is essential for vascular integrity and immune defence1,2. Although the process of platelet formation by fragmenting megakaryocytes (MKs; thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms required to constantly replenish the pool of MKs by their progenitor cells (megakaryopoiesis) remains unclear3,4. Here we use intravital imaging to track the cellular dynamics of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs) as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver IFNα to the MK niche triggering local on-demand proliferation and maturation of MK progenitors. This pDC-dependent feedback loop is crucial for MK …

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 …