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Bueso Ramos

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https://www.readbyqxmd.com/read/29134664/a-phase-ii-trial-of-ruxolitinib-in-combination-with-azacytidine-in-myelodysplastic-syndrome-myeloproliferative-neoplasms
#1
Rita Assi, Hagop M Kantarjian, Guillermo Garcia-Manero, Jorge E Cortes, Naveen Pemmaraju, Xuemei Wang, Graciela Nogueras-Gonzalez, Elias Jabbour, Prithviraj Bose, Tapan Kadia, Courtney D Dinardo, Keyur Patel, Carlos Bueso-Ramos, Lingsha Zhou, Sherry Pierce, Romany Gergis, Carla Tuttle, Gautam Borthakur, Zeev Estrov, Rajyalakshmi Luthra, Juliana Hidalgo-Lopez, Srdan Verstovsek, Naval Daver
Ruxolitinib and azacytidine target distinct disease manifestations of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPNs). Patients with MDS/MPNs initially received ruxolitinib BID (doses based on platelets count), continuously in 28-day cycles for the first 3 cycles. Azacytidine 25 mg/m(2) (Day 1-5) intravenously or subcutaneously was recommended to be added to each cycle starting cycle 4 and could be increased to 75 mg/m(2) (Days 1-5) for disease control. Azacytidine could be started earlier than cycle 4 and/or at higher dose in patients with rapidly proliferative disease or with elevated blasts...
November 14, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28885734/chronic-myelomonocytic-leukemia-masquerading-as-cutaneous-indeterminate-dendritic-cell-tumor-expanding-the-spectrum-of-skin-lesions-in-chronic-myelomonocytic-leukemia
#2
Sanam Loghavi, Jonathan L Curry, Guillermo Garcia-Manero, Keyur P Patel, Jie Xu, Joseph D Khoury, Carlos A Torres-Cabala, Priyadharsini Nagarajan, Phyu P Aung, Bernard R Gibson, Brandon P Goodwin, Brent C Kelly, Brinda R Korivi, L Jeffrey Medeiros, Victor G Prieto, Hagop M Kantarjian, Carlos E Bueso-Ramos, Michael T Tetzlaff
Chronic myelomonocytic leukemia (CMML) is a hematopoietic stem cell neoplasm exhibiting both myelodysplastic and myeloproliferative features. Cutaneous involvement by CMML is critical to recognize as it typically is a harbinger of disease progression and an increased incidence of transformation to acute myeloid leukemia. Cutaneous lesions of CMML exhibit heterogeneous histopathologic features that can be challenging to recognize as CMML. We describe a 67-year-old man with a 3-year history of CMML who had been managed on single-agent azacitidine with stable disease before developing splenomegaly and acute onset skin lesions...
September 8, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28774880/randomized-phase-2-study-of-low-dose-decitabine-vs-low-dose-azacitidine-in-lower-risk-mds-and-mds-mpn
#3
RANDOMIZED CONTROLLED TRIAL
Elias Jabbour, Nicholas J Short, Guillermo Montalban-Bravo, Xuelin Huang, Carlos Bueso-Ramos, Wei Qiao, Hui Yang, Chong Zhao, Tapan Kadia, Gautam Borthakur, Naveen Pemmaraju, Koji Sasaki, Zeev Estrov, Jorge Cortes, Farhad Ravandi, Yesid Alvarado, Rami Komrokji, Mikkael A Sekeres, David P Steensma, Amy DeZern, Gail Roboz, Hagop Kantarjian, Guillermo Garcia-Manero
Hypomethylating agents (HMAs) improve survival in patients with higher-risk myelodysplastic syndromes (MDS) but are less well-studied in lower-risk disease. We compared the safety and efficacy of low-dose decitabine vs low-dose azacitidine in this group of patients. Adults with low- or intermediate 1-risk MDS or MDS/myeloproliferative neoplasm (MPN), including chronic myelomonocytic leukemia, according to the International Prognostic Scoring System, were randomly assigned using a Bayesian adaptive design to receive either azacitidine 75 mg/m(2) intravenously/subcutaneously daily or decitabine 20 mg/m(2) intravenously daily for 3 consecutive days on a 28-day cycle...
September 28, 2017: Blood
https://www.readbyqxmd.com/read/28760297/progress-in-myelodysplastic-syndromes-clinicopathologic-correlations-and-immune%C3%A2-checkpoints
#4
Juliana E Hidalgo-López, Rashmi Kanagal-Shamanna, Andrés E Quesada, Beenu Thakral, Zhihong Hu, Takayuki Mitsuhashi, Mariko Yabe, Guillermo Garcia-Manero, Carlos E Bueso-Ramos
BACKGROUND: Myelodysplastic syndromes (MDS) are a group of clonal neoplasms characterized by ineffective hematopoiesis. Hypomethylating agent (HMA) therapy is one of the mainstays of MDS therapy. Failure of HMA therapy is related to poor outcome; hence, new therapeutic approaches are warranted in these patients. In MDS, the immune system has a pivotal role in modulation of hematopoiesis and clonal expansion. In neoplastic conditions, immune checkpoint (PD-1 and CTLA4 molecules) hide tumor cells from immune surveillance...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28685840/european-leukemianet-study-on-the-reproducibility-of-bone-marrow-features-in-masked-polycythemia-vera-and-differentiation-from-essential-thrombocythemia
#5
Hans Michael Kvasnicka, Attilio Orazi, Juergen Thiele, Giovanni Barosi, Carlos E Bueso-Ramos, Alessandro M Vannucchi, Robert P Hasserjian, Jean-Jacques Kiladjian, Umberto Gianelli, Richard Silver, Tariq I Mughal, Tiziano Barbui
The purpose of the study was to assess consensus and interobserver agreement among an international panel of six hematopathologists regarding characterization and reproducibility of bone marrow (BM) histologic features used to diagnose early stage myeloproliferative neoplasms, in particular differentiation of so-called masked/prodromal polycythemia vera (mPV) from JAK2-mutated essential thrombocythemia (ET). The six members of the hematopathology panel evaluated 98 BM specimens independently and in a blinded fashion without knowledge of clinical data...
October 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28679949/aml-induced-osteogenic-differentiation-in-mesenchymal-stromal-cells-supports-leukemia-growth
#6
V Lokesh Battula, Phuong M Le, Jeffrey C Sun, Khoa Nguyen, Bin Yuan, Ximin Zhou, Sonali Sonnylal, Teresa McQueen, Vivian Ruvolo, Keith A Michel, Xiaoyang Ling, Rodrigo Jacamo, Elizabeth Shpall, Zhiqiang Wang, Arvind Rao, Gheath Al-Atrash, Marina Konopleva, R Eric Davis, Melvyn A Harrington, Catherine W Cahill, Carlos Bueso-Ramos, Michael Andreeff
Genotypic and phenotypic alterations in the bone marrow (BM) microenvironment, in particular in osteoprogenitor cells, have been shown to support leukemogenesis. However, it is unclear how leukemia cells alter the BM microenvironment to create a hospitable niche. Here, we report that acute myeloid leukemia (AML) cells, but not normal CD34+ or CD33+ cells, induce osteogenic differentiation in mesenchymal stromal cells (MSCs). In addition, AML cells inhibited adipogenic differentiation of MSCs. Mechanistic studies identified that AML-derived BMPs activate Smad1/5 signaling to induce osteogenic differentiation in MSCs...
July 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28669490/ilf2-is-a-regulator-of-rna-splicing-and-dna-damage-response-in-1q21-amplified-multiple-myeloma
#7
Matteo Marchesini, Yamini Ogoti, Elena Fiorini, Anil Aktas Samur, Luigi Nezi, Marianna D'Anca, Paola Storti, Mehmet Kemal Samur, Irene Ganan-Gomez, Maria Teresa Fulciniti, Nipun Mistry, Shan Jiang, Naran Bao, Valentina Marchica, Antonino Neri, Carlos Bueso-Ramos, Chang-Jiun Wu, Li Zhang, Han Liang, Xinxin Peng, Nicola Giuliani, Giulio Draetta, Karen Clise-Dwyer, Hagop Kantarjian, Nikhil Munshi, Robert Orlowski, Guillermo Garcia-Manero, Ronald A DePinho, Simona Colla
Amplification of 1q21 occurs in approximately 30% of de novo and 70% of relapsed multiple myeloma (MM) and is correlated with disease progression and drug resistance. Here, we provide evidence that the 1q21 amplification-driven overexpression of ILF2 in MM promotes tolerance of genomic instability and drives resistance to DNA-damaging agents. Mechanistically, elevated ILF2 expression exerts resistance to genotoxic agents by modulating YB-1 nuclear localization and interaction with the splicing factor U2AF65, which promotes mRNA processing and the stabilization of transcripts involved in homologous recombination in response to DNA damage...
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28659335/bone-marrow-pathologic-abnormalities-in-familial-platelet-disorder-with-propensity-for-myeloid-malignancy-and-germline-runx1-mutation
#8
Rashmi Kanagal-Shamanna, Sanam Loghavi, Courtney D DiNardo, L Jeffrey Medeiros, Guillermo Garcia-Manero, Elias Jabbour, Mark J Routbort, Rajyalakshmi Luthra, Carlos E Bueso-Ramos, Joseph D Khoury
A subset of patients with familial platelet disorder with propensity to myeloid malignancy and germline RUNX1 mutation develops hematological malignancies, often myelodysplastic syndrome/acute myeloid leukemia, currently recognized in the 2016 WHO classification. Patients who develop hematologic malignancies are typically young, respond poorly to conventional therapy, and need allogeneic stem cell transplant from non-familial donors. Understanding the spectrum of bone marrow morphologic and genetic findings in these patients is critical to ensure diagnostic accuracy and develop criteria to recognize the onset of hematologic malignancies, particularly myelodysplastic syndrome...
October 2017: Haematologica
https://www.readbyqxmd.com/read/28596259/morphologic-and-molecular-characteristics-of-de-novo-aml-with-jak2-v617f-mutation
#9
Juliana E Hidalgo-López, Rashmi Kanagal-Shamanna, L Jeffrey Medeiros, Zeev Estrov, C Cameron Yin, Srdan Verstovsek, Sergej Konoplev, Jeffrey L Jorgensen, Mohammad M Mohammad, Roberto N Miranda, Chong Zhao, John Lee, Zhuang Zuo, Carlos E Bueso-Ramos
Background:JAK2 V617F mutation (mut) in acute myeloid leukemia (AML) is rare. We describe the clinicopathologic findings of a single-institution series of 11 de novo AML cases with JAK2 V617. Methods: We identified cases of de novo AML with JAK2 V617F over a 10-year period. We reviewed diagnostic peripheral blood and bone marrow (BM) morphologic, cytogenetic, and molecular studies, including next-generation sequencing. The control group consisted of 12 patients with JAK2 wild-type (wt) AML matched for age, sex, and diagnosis...
June 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28556489/factors-associated-with-risk-of-central-nervous-system-relapse-in-patients-with-non-core-binding-factor-acute-myeloid-leukemia
#10
Elias Jabbour, Naval Guastad Daver, Nicholas James Short, Xuelin Huang, Hsiang-Chun Chen, Abhishek Maiti, Farhad Ravandi, Jorge Cortes, Simon Abi Aad, Guillermo Garcia-Manero, Zeev Estrov, Tapan Kadia, Susan O'Brien, Bouthaina Dabaja, Carlos Bueso-Ramos, Paolo Strati, Carol Bivins, Sherry Pierce, Hagop Kantarjian
Central nervous system (CNS) relapse is uncommon in patients with acute myeloid leukemia (AML) with the use of high-dose cytarabine containing chemotherapy regimens. The clinical and molecular features associated with a higher risk of CNS relapse are not well defined. We assessed the incidence and outcome of CNS relapses among 1245 patients with relapsed/refractory AML referred to our institution between 2000 and 2014. CNS leukemia relapse was observed in 51 patients (4.1%). Using a multivariate regression model and after adjusting for age, FLT3-ITD mutation (OR = 2...
September 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28551329/myeloproliferative-neoplasms-with-t-8-22-p11-2-q11-2-bcr-fgfr1-a-meta-analysis-of-20-cases-shows-cytogenetic-progression-with-b-lymphoid-blast-phase
#11
REVIEW
Ximena Montenegro-Garreaud, Roberto N Miranda, Alexandra Reynolds, Guilin Tang, Sa A Wang, Mariko Yabe, Wei Wang, Lianghua Fang, Carlos E Bueso-Ramos, Pei Lin, L Jeffrey Medeiros, Xinyan Lu
Rearrangements of FGFR1 result in the 8p11 myeloproliferative syndrome, a group of rare diseases that features a myeloproliferative neoplasm (MPN) that commonly progresses to lymphoblastic leukemia/lymphoma or acute myeloid leukemia. The most common partner of FGFR1 is ZMYM2, and patients with the ZMYM2-FGFR1 fusion often present with MPN and T-lymphoblastic lymphoma. There are 14 other partners that can fuse with FGFR1, and of interest is the BCR-FGFR1 fusion that results from t(8;22)(p11.2;q11.2). Patients with t(8;22) often show leukocytosis and present with an MPN resembling chronic myeloid leukemia or very rarely, with B-lymphoblastic leukemia (B-ALL)...
July 2017: Human Pathology
https://www.readbyqxmd.com/read/28548124/oligomonocytic-chronic-myelomonocytic-leukemia-chronic-myelomonocytic-leukemia-without-absolute-monocytosis-displays-a-similar-clinicopathologic-and-mutational-profile-to-classical-chronic-myelomonocytic-leukemia
#12
Julia T Geyer, Wayne Tam, Yen-Chun Liu, Zhengming Chen, Sa A Wang, Carlos Bueso-Ramos, Jean Oak, Daniel A Arber, Eric Hsi, Heesun J Rogers, Katherine Levinson, Adam Bagg, Duane C Hassane, Robert P Hasserjian, Attilio Orazi
Chronic myelomonocytic leukemia is characterized by persistent absolute monocytosis (≥1 × 10(9)/l) in the peripheral blood and dysplasia in ≥1 lineages. In the absence of dysplasia, an acquired clonal genetic abnormality is required or causes for reactive monocytosis have to be excluded. Oligomonocytic chronic myelomonocytic leukemia showing increased monocytes but no absolute monocytosis in the peripheral blood occurs occasionally. These cases are likely classified as myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm, unclassifiable...
September 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28495918/bone-marrow-morphology-is-a-strong-discriminator-between-chronic-eosinophilic-leukemia-not-otherwise-specified-and-reactive-idiopathic-hypereosinophilic-syndrome
#13
Sa A Wang, Robert P Hasserjian, Wayne Tam, Albert G Tsai, Julia T Geyer, Tracy I George, Kathryn Foucar, Heesun J Rogers, Eric D Hsi, Bryan A Rea, Adam Bagg, Carlos E Bueso-Ramos, Daniel A Arber, Srdan Verstovsek, Attilio Orazi
Chronic eosinophilic leukemia, not otherwise specified can be difficult to distinguish from idiopathic hypereosinophilic syndrome according to the current World Health Organization guideline. To examine whether the morphological features of bone marrow might aid in the differential diagnosis of these two entities, we studied a total of 139 patients with a diagnosis of chronic eosinophilic leukemia, not otherwise specified (n=17) or idiopathic hypereosinophilic syndrome (n=122). As a group, abnormal bone marrow morphological features, resembling myelodysplastic syndromes, myeloproliferative neoplasm or myelodysplastic/myeloproliferative neoplasm, were identified in 40/139 (27%) patients: 16 (94%) of those with chronic eosinophilic leukemia and 24 (20%) of those with hypereosinophilic syndrome...
August 2017: Haematologica
https://www.readbyqxmd.com/read/28495642/feasibility-of-lenalidomide-therapy-for-persistent-chronic-lymphocytic-leukemia-after-allogeneic-transplantation
#14
Maria R Khouri, Elias J Jabbour, Alison M Gulbis, Francesco Turturro, Celina Ledesma, Martin Korbling, Barry I Samuels, Sairah Ahmed, Amin M Alousi, Stefan O Ciurea, David Marin, Krina K Patel, Uday R Popat, Carlos E Bueso-Ramos, Roland L Bassett, Issa F Khouri
In patients with chronic lymphocytic leukemia (CLL), persistence of disease after allogeneic stem cell transplantation (alloSCT) can result in poor outcomes. In an effort to improve these outcomes, patients with persistent CLL who were 90 to 100 days beyond alloSCT with no evidence of graft-versus-host-disease (GVHD) were randomized to receive lenalidomide or standard care (withdrawal of immunosuppression followed by donor lymphocyte infusion). Lenalidomide was initiated at 5 mg every other day and increased to 10 mg daily, if tolerated, in each patient...
August 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28473622/characteristics-and-clinical-significance-of-cytogenetic-abnormalities-in-polycythemia-vera
#15
Guilin Tang, Juliana E Hidalgo Lopez, Sa A Wang, Shimin Hu, Junsheng Ma, Sherry Pierce, Wenli Zuo, Adrian Alejandro Carballo-Zarate, C Cameron Yin, Zhenya Tang, Shaoying Li, L Jeffrey Medeiros, Srdan Verstovsek, Carlos E Bueso-Ramos
UP to 20% of patients with polycythemia vera have karyotypic abnormalities at time of initial diagnosis. However, the cytogenetic abnormalities in polycythemia vera have not been well-characterized and their prognostic impact is largely unknown. In this study, we aimed to address these questions using a large cohort of polycythemia vera patients with cytogenetic information available. The study included 422 patients, 271 in polycythaemic phase, 112 post-polycythaemic myelofibrosis, 11 accelerated phase, and 28 blast phase...
May 4, 2017: Haematologica
https://www.readbyqxmd.com/read/28428103/characteristics-and-clinical-implications-of-reactive-germinal-centers-in-the-bone-marrow
#16
Rose Lou Marie C Agbay, L Jeffrey Medeiros, Joseph D Khoury, Alireza Salem, Carlos E Bueso-Ramos, Sanam Loghavi
Reactive germinal centers (GCs) in the bone marrow (BM) have been described in patients with autoimmune disorders, infections, malignancies and following certain drug therapies, or as an isolated finding without obvious underlying disease. In this study, we describe the clinical conditions in which reactive GCs occur in BM samples, and their topography and accompanying laboratory and ancillary findings in the setting of a cancer center. We identified 32 BM specimens with reactive GCs with an estimated frequency of <0...
April 17, 2017: Human Pathology
https://www.readbyqxmd.com/read/28382648/characteristics-management-and-outcomes-of-patients-with-follicular-dendritic-cell-sarcoma
#17
Preetesh Jain, Sarah A Milgrom, Keyur P Patel, Loretta Nastoupil, Luis Fayad, Michael Wang, Chelsea C Pinnix, Bouthaina S Dabaja, Grace L Smith, Jun Yu, Shimin Hu, Carlos E Bueso Ramos, Rashmi Kanagal-Shamanna, L Jeffrey Medeiros, Yasuhiro Oki, Nathan Fowler
Dendritic cell sarcomas are rare tumours of antigen presenting cells. Data regarding their biology, management and outcomes are sparse. We analysed 66 patients with follicular dendritic cell sarcoma (FDCS). Six patients also had Castleman disease, 9 had another malignancy and 13 had an autoimmune disease. Fifty-four per cent of patients presented with localized disease and 46% with systemic involvement. The median progression-free (PFS) and overall survival (OS) following frontline therapy was 21 and 50 months, respectively...
August 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28375434/most-myeloid-neoplasms-with-deletion-of-chromosome-16q-are-distinct-from-acute-myeloid-leukemia-with-inv-16-p13-1q22-a-bone-marrow-pathology-group-multicenter-study
#18
MULTICENTER STUDY
Heesun J Rogers, Eric D Hsi, Guilin Tang, Sa A Wang, Carlos E Bueso-Ramos, Daniel Lubin, Jennifer J D Morrissette, Adam Bagg, Durga P Cherukuri, Tracy I George, LoAnn Peterson, Yen-Chun Liu, Susan Mathew, Attilio Orazi, Robert P Hasserjian
Objectives: Isolated deletion of the long arm of chromosome 16 (del(16q)) is rare in myeloid neoplasms (MNs) and was historically considered a variant of inv(16)(p13.1q22) (inv(16)), a subtype of acute myeloid leukemia (AML) associated with CBFB-MYH11 rearrangement and favorable prognosis. This study aims to determine clinicopathologic characteristics of patients with isolated del(16q) in MNs in comparison to AMLs with isolated inv(16). Methods: Clinicopathologic features were retrospectively reviewed in 18 MNs with del(16q) and 34 AMLs with inv(16) patients from seven institutions...
April 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28370157/an-exploratory-clinical-trial-of-bortezomib-in-patients-with-lower-risk-myelodysplastic-syndromes
#19
May Daher, Juliana Elisa Hidalgo Lopez, Jasleen K Randhawa, Kausar Jabeen Jabbar, Yue Wei, Naveen Pemmaraju, Gautam Borthakur, Tapan Kadia, Marina Konopleva, Hagop M Kantarjian, Katherine Hearn, Zeev Estrov, Steven Reyes, Carlos E Bueso-Ramos, Guillermo Garcia-Manero
Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis and an increased risk of transformation. Few effective therapies are available for lower risk MDS patients, especially after the failure of hypomethylating agents. MDS progenitor cells are dependent on the nuclear factor-κB (NF-κB) for survival, which makes it an attractive therapeutic target. As a proteosomal inhibitor, bortezomib is thought to have inhibitory activity against NF-κB. We designed a proof-of-principle study of subcutaneous (SC) bortezomib in lower risk MDS patients with evidence of NF-κB activation in their bone marrow...
July 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28370097/natural-history-of-chronic-myelomonocytic-leukemia-treated-with-hypomethylating-agents
#20
Ana Alfonso, Guillermo Montalban-Bravo, Koichi Takahashi, Elias J Jabbour, Tapan Kadia, Farhad Ravandi, Jorge Cortes, Zeev Estrov, Gautam Borthakur, Naveen Pemmaraju, Marina Konopleva, Carlos Bueso-Ramos, Sherry Pierce, Hagop Kantarjian, Guillermo Garcia-Manero
Hypomethylating agents (HMA) are the most commonly used therapeutic intervention in chronic myelomonocytic leukemia (CMML). Due to the lack of CMML-specific clinical trials, the impact of these agents in the natural history of CMML is not fully understood. We present the largest retrospective series of CMML (n = 151) treated with HMA. Mean age at diagnosis was 69 years (range 50-88). According to the CMML-specific prognostic scoring system (CPSS): 17 (15%) were low-risk, 45 (39%) intermediate-1 risk, 42 (36%) intermediate-2, and 12 (10%) high-risk...
July 2017: American Journal of Hematology
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