Hematology Commons^™

Effect Of Age On The Pharmacokinetics Of Busulfan In Patients Undergoing Hematopoietic Cell Transplantation; An Alliance Study (Calgb 10503, 19808, And 100103), J. H. Beumer, K. Owzar, L. D. Lewis, C. Jiang, J. L. Holleran, S. M. Christner, W. Blum, S. Devine, J. E. Kolitz, M. J. Egorin, +5 Additional Authors

Journal Articles

Older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome have often been excluded from myeloablative-conditioning regimens containing busulfan because of non-disease-related morbidity and mortality. We hypothesized that busulfan clearance (BuCL) in older patients (> 60 years) would be reduced compared to that in younger patients, potentially explaining observed differences in busulfan tolerability. AML patients in three CALGB hematopoietic cell transplantation studies were treated with a conditioning regimen using IV busulfan, dosed at 0.8 mg/kg. Plasma busulfan concentrations were determined by LC-MS and analyzed by non-compartmental methods. BuCL was normalized to actual (ABW), ideal (IBW), or corrected (CBW) body weight …

Epigenetics Meets Genetics In Acute Myeloid Leukemia: Clinical Impact Of A Novel Seven-Gene Score, G. Marcucci, P. Yan, K. Maharry, D. Frankhouser, D. Nicolet, K. H. Metzeler, J. Kohlschmidt, K. Mrozek, J. E. Kolitz, C. D. Bloomfield, +21 Additional Authors

Journal Articles

Purpose Molecular risk stratification of acute myeloid leukemia (AML) is largely based on genetic markers. However, epigenetic changes, including DNA methylation, deregulate gene expression and may also have prognostic impact. We evaluated the clinical relevance of integrating DNA methylation and genetic information in AML. Methods Next-generation sequencing analysis of methylated DNA identified differentially methylated regions (DMRs) associated with prognostic mutations in older ( 60 years) cytogenetically normal (CN) patients with AML (n = 134). Genes with promoter DMRs and expression levels significantly associated with outcome were used to compute a prognostic gene expression weighted summary score that was tested and …

Lenalidomide And Rituximab For The Initial Treatment Of Patients With Chronic Lymphocytic Leukemia: A Multicenter Clinical-Translational Study From The Chronic Lymphocytic Leukemia Research Consortium, D. F. James, L. Werner, J. R. Brown, W. G. Wierda, J. C. Barrientos, J. E. Castro, A. Greaves, A. J. Johnson, K. R. Rai, T. J. Kipps, +2 Additional Authors

Journal Articles

Purpose Lenalidomide is an immunomodulatory agent with therapeutic activity in chronic lymphocytic leukemia (CLL). In preclinical models, lenalidomide acted synergistically with rituximab. The CLL Research Consortium initiated a phase II study to evaluate this combination in treatmentnaive patients. Patients and Methods Lenalidomide was initiated at 2.5 mg/day and was escalated based on treatment tolerability to a maximum of 10 mg/day, for 21 days/cycle, for a maximum of seven cycles. Rituximab was administered at the end of cycle 1 and was continued for seven cycles. Patients received allopurinol and aspirin for prophylaxis. Results Sixty-nine patients enrolled onto one of two age-specific …

Ighv1-69 B Cell Chronic Lymphocytic Leukemia Antibodies Cross-React With Hiv-1 And Hepatitis C Virus Antigens As Well As Intestinal Commensal Bacteria, K. K. Hwang, A. M. Trama, D. M. Kozink, S. L. Allen, K. R. Rai, R. Catera, X. J. Yan, C. C. Chu, N. Chiorazzi, B. F. Haynes, +12 Additional Authors

Journal Articles

IGHV1-B-cell chronic lymphocytic leukemia (B-CLL) patients expressing unmutated immunoglobulin heavy variable regions (IGHVs) use the IGHV1-69 B cell receptor (BCR) in 25% of cases. Since HIV-1 envelope gp41 antibodies also frequently use IGHV1-69 gene segments, we hypothesized that IGHV1-69 B-CLL precursors may contribute to the gp41 B cell response during HIV-1 infection. To test this hypothesis, we rescued 5 IGHV1-69 unmutated antibodies as heterohybridoma IgM paraproteins and as recombinant IgG(1) antibodies from B-CLL patients, determined their antigenic specificities and analyzed BCR sequences. IGHV1-69 B-CLL antibodies were enriched for reactivity with HIV-1 envelope gp41, influenza, hepatitis C virus E2 protein and …

Igm Myeloma Or Waldenstrom's Macroglobulinemia Is The Big Question?, V. R. Bhatt, S. Murukutla, M. Naqi, S. Pant, S. Kedia, T. Terjanian

Journal Articles

ABSTRACT: Although critical from therapeutic and prognostic perspectives, differentiating IgM Myeloma (MM) from Waldenstrom's macroglobulinemia (WM) is fraught with failure. WM can usually be distinguished from IgM MM by the lymphoplasmacytic versus pure plasmacytic morphology, absent versus present lytic bone lesions, and immunophenotypic findings. However, all these features have their own limitations; hence, it requires constant vigilance and periodic re-evaluation. Here we describe a case of a 70-year-old woman initially diagnosed as smoldering IgM MM, who eventually turned out to have WM.

Expression And Prognostic Impact Of Lncrnas In Acute Myeloid Leukemia, R. Garzon, S. Volinia, D. Papaioannou, D. Nicolet, J. Kohlschmidt, P. S. Yan, K. Mrozek, D. Bucci, J. E. Kolitz, C. D. Bloomfield, +15 Additional Authors

Journal Articles

Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides, located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. LncRNAs are involved in numerous biological roles including imprinting, epigenetic regulation, apoptosis, and cell cycle. To determine whether lncRNAs are associated with clinical features and recurrent mutations in older patients (aged >/=60 y) with cytogenetically normal (CN) acute myeloid leukemia (AML), we evaluated lncRNA expression in 148 untreated older CN-AML cases using a custom microarray platform. An independent set of 71 untreated older patients with CN-AML was used to validate the outcome scores using RNA sequencing. Distinctive …

More Than 9 Years Of Continuous Trastuzumab Treatment In Metastatic Breast Cancer Without Cardiac Toxicity: A Case Report And Literature Review, F. Badulescu, A. Badulescu, D. Paul, C. F. Popescu, C. Florescu

Journal Articles

The main concern of long-term use of trastuzumab remains its association with potential cardiac side effects. Although these side effects are real, they are probably overemphasized. We report the case of a woman with metastatic breast cancer, who is currently in complete remission, and who received trastuzumab continuously for more than 9 years, without any significant cardiac toxicity.

Outcomes Of Temporary Interruption Of Rivaroxaban Compared With Warfarin In Patients With Nonvalvular Atrial Fibrillation, M. W. Sherwood, J. D. Douketis, M. R. Patel, J. P. Piccini, A. S. Hellkamp, Y. Lokhnygina, A. C. Spyropoulos, G. J. Hankey, D. E. Singer, R. C. Becker, +4 Additional Authors

Journal Articles

Background During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. Methods and Results In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including …

Prolonged Survival In Metastatic Colorectal Cancer Following Chemotherapy, D. Paul, M. Gold, N. Nouraddin

Journal Articles

KEY CLINICAL MESSAGE: The cost of treating metastatic colorectal cancer has increased significantly after the introduction of targeted antivascular therapies. We report the unusual case of a patient with colorectal cancer with several large liver metastases at diagnosis, who was cured after removal of the primary tumor and treatment with 5-FU/LV only.

Resistance Mechanisms For The Bruton's Tyrosine Kinase Inhibitor Ibrutinib, J. A. Woyach, R. R. Furman, T. M. Liu, H. G. Ozer, M. Zapatka, A. S. Ruppert, L. Xue, D. H. H. Li, J. C. Barrientos, J. C. Byrd, +15 Additional Authors

Journal Articles

BACKGROUND Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (BTK) and is effective in chronic lymphocytic leukemia (CLL). Resistance to irreversible kinase inhibitors and resistance associated with BTK inhibition have not been characterized. Although only a small proportion of patients have had a relapse during ibrutinib therapy, an understanding of resistance mechanisms is important. We evaluated patients with relapsed disease to identify mutations that may mediate ibrutinib resistance. METHODS We performed whole-exome sequencing at baseline and the time of relapse on samples from six patients with acquired resistance to ibrutinib therapy. We then performed functional analysis of identified mutations. …

Gas6 Expression Identifies High-Risk Adult Aml Patients: Potential Implications For Therapy, S. P. Whitman, J. Kohlschmidt, K. Maharry, S. Volinia, K. Mrozek, D. Nicolet, S. Schwind, H. Becker, J. E. Kolitz, C. D. Bloomfield, +11 Additional Authors

Journal Articles

Emerging data demonstrate important roles for the TYRO3/AXL/MERTK receptor tyrosine kinase (TAM RTK) family in diverse cancers. We investigated the prognostic relevance of GAS6 expression, encoding the common TAM RTK ligand, in 270 adults (n=71 aged <60 >years; n=199 aged >= 60 years) with de novo cytogenetically normal acute myeloid leukemia (CN-AML). Patients expressing GAS6 (GAS6+), especially those aged >= 60 years, more often failed to achieve a complete remission (CR). In all patients, GAS6+ patients had shorter disease-free (DFS) and overall (OS) survival than patients without GAS6 expression (GAS6-). After adjusting for other prognostic markers, GAS6+ predicted CR failure (P=0.02), …

Ibrutinib Versus Ofatumumab In Previously Treated Chronic Lymphoid Leukemia, J. C. Byrd, J. R. Brown, S. O'Brien, J. C. Barrientos, N. E. Kay, N. M. Reddy, S. Coutre, C. S. Tam, S. P. Mulligan, P. Hillmen, +25 Additional Authors

Journal Articles

Background In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton's tyrosine kinase, in patients at risk for a poor outcome. Methods In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response …

Idelalisib And Rituximab In Relapsed Chronic Lymphocytic Leukemia, R. R. Furman, J. P. Sharman, S. E. Coutre, B. D. Cheson, J. M. Pagel, P. Hillmen, J. C. Barrientos, A. D. Zelenetz, T. J. Kipps, S. M. O'Brien, +17 Additional Authors

Journal Articles

BackgroundPatients with relapsed chronic lymphocytic leukemia (CLL) who have clinically significant coexisting medical conditions are less able to undergo standard chemotherapy. Effective therapies with acceptable side-effect profiles are needed for this patient population. MethodsIn this multicenter, randomized, double-blind, placebo-controlled, phase 3 study, we assessed the efficacy and safety of idelalisib, an oral inhibitor of the delta isoform of phosphatidylinositol 3-kinase, in combination with rituximab versus rituximab plus placebo. We randomly assigned 220 patients with decreased renal function, previous therapy-induced myelosuppression, or major coexisting illnesses to receive rituximab and either idelalisib (at a dose of 150 mg) or placebo twice daily. …

18 F-Fluorothymidine Uptake In Follicular Lymphoma And Error-Prone Dna Repair, Marielle J. Wondergem, Ken Herrmann, Sergei Syrbu, Josee M. Zijlstra, Nikie Hoetjes, Otto S. Hoekstra, Saskia Agm Cillessen, Laura M. Mosenbergen, Andreas K. Buck, Julie M. Vose, Malik E. Juweid

Journal Articles: Oncology and Hematology

BACKGROUND:

We observed a disproportional 18 F-fluorothymidine (F-FLT) uptake in follicular lymphoma (FL) relative to its low cell proliferation. We tested the hypothesis that the 'excess' uptake of 18 F-FLT in FL is related to error-prone DNA repair and investigated whether this also contributes to 18 F-FLT uptake in diffuse large B cell lymphoma (DLBCL).

METHODS:

We performed immunohistochemical stainings to assess the pure DNA replication marker MIB-1 as well as markers of both DNA replication and repair like PCNA, TK-1 and RPA1 on lymph node biopsies of 27 FLs and 35 DLBCLs. In 7 FL and 15 DLBCL patients, …

Deferiprone Versus Deferoxamine In Sickle Cell Disease: Results From A 5-Year Long-Term Italian Multi-Center Randomized Clinical Trial., Giusi Calvaruso, Angela Vitrano, Rosario Di Maggio, Samir K. Ballas, Martin H Steinberg, Paolo Rigano, Massimiliano Sacco, Paul Telfer, Disma Renda, Rita Barone, Aurelio Maggio

Cardeza Foundation for Hematologic Research

Blood transfusion and iron chelation currently represent a supportive therapy to manage anemia, vasculopathy and vaso-occlusion crises in Sickle-Cell-Disease. Here we describe the first 5-year long-term randomized clinical trial comparing Deferiprone versus Deferoxamine in patients with Sickle-Cell-Disease. The results of this study show that Deferiprone has the same effectiveness as Deferoxamine in decreasing body iron burden, measured as repeated measurements of serum ferritin concentrations on the same patient over 5-years and analyzed according to the linear mixed-effects model (LMM) (p=0.822). Both chelators are able to decrease, significantly, serum ferritin concentrations, during 5-years, without any effect on safety (p=0.005). Moreover, although …

Disposable Platform Provides Visual And Color-Based Point-Of-Care Anemia Self-Testing, Erika A. Tyburski, Scott E. Gillespie, William A. Stoy, Robert G. Mannino, Alexander J. Weiss, Alexa F. Siu, Rayford H. Bulloch, Karthik Thota, Anyela Cardenas, Wilena Session, Hanna J. Khoury, Siobhán O'Connor, Silvia T. Bunting, Jeanne Boudreaux, Craig R. Forest, Manila Gaddh, Traci Leong, L. Andrew Lyon, Wilbur A. Lam

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Anemia, or low blood hemoglobin (Hgb) levels, afflicts 2 billion people worldwide. Currently, Hgb levels are typically measured from blood samples using hematology analyzers, which are housed in hospitals, clinics, or commercial laboratories and require skilled technicians to operate. A reliable, inexpensive point-of-care (POC) Hgb test would enable cost-effective anemia screening and chronically anemic patients to self-monitor their disease. We present a rapid, standalone, and disposable POC anemia test that, via a single drop of blood, outputs color-based visual results that correlate with Hgb levels.

METHODS. We tested blood from 238 pediatric and adult patients with anemia of varying …

Ewing's Sarcoma Arising From The Adrenal Gland In A Young Male: A Case Report, Muhammad Nauman Zahir, Tayyaba Zehra Ansari, Tariq Moatter, Wasim Memon, Shahid Pervez

Section of Haematology/Oncology

Background: Ewing's sarcoma uncommonly arises from extraosseous soft tissue or parenchymal organs. Primary adrenal Ewing's Sarcoma, although very rare, is extremely aggressive and commonly fatal.

CASE PRESENTATION: A 17 year old Pakistani male was referred to the outpatient oncology clinic at our center with a three month history of concomitant pain, swelling and dragging sensation in the right hypochondrium. Abdominal examination revealed a large, firm mass in the right hypochondrium extending into the right lumbar region and epigastrium. His genital exam was unremarkable and there were no stigmata of hepatic or adrenal disease.Computed tomography scans revealed a large peripherally …

Racial Differences In Human Platelet Par4 Reactivity Reflect Expression Of Pctp And Mir-376c., Leonard Edelstein, Lukas M Simon, Raúl Teruel Montoya, Michael Holinstat, Edward S Chen, Angela Bergeron, Xianguo Kong, Srikanth Nagalla, Narla Mohandas, David E Cohen, Jing-Fei Dong, Chad Shaw, Paul Bray

Cardeza Foundation for Hematologic Research

Racial differences in the pathophysiology of atherothrombosis are poorly understood. We explored the function and transcriptome of platelets in healthy black (n = 70) and white (n = 84) subjects. Platelet aggregation and calcium mobilization induced by the PAR4 thrombin receptor were significantly greater in black subjects. Numerous differentially expressed RNAs were associated with both race and PAR4 reactivity, including PCTP (encoding phosphatidylcholine transfer protein), and platelets from black subjects expressed higher levels of PC-TP protein. PC-TP inhibition or depletion blocked PAR4- but not PAR1-mediated activation of platelets and megakaryocytic cell lines. miR-376c levels were differentially expressed by race and …

Characterization Of Prophylactic Antiemetic Regimens In Pediatric Patients Receiving Moderately And Highly Emetogenic Chemotherapy, Jessica Degiacomo Pharmd, Kristin M. Held Pharmd, Bcop

Department of Pharmacy

No abstract provided.

Neuropathy, Neuropathic Pain, And Sickle Cell Disease., Samir K. Ballas, Deepika S Darbari

Cardeza Foundation for Hematologic Research

No abstract provided.