Hematology Commons^™

In Support Of A Patient-Driven Initiative And Petition To Lower The High Price Of Cancer Drugs, A. Tefferi, K. Rai, A. I. Schafer, C. Schiffer, M. A. Sekeres, L. L. Siu, F. M. Stewart, M. Thompson, J. M. Vose, P. H. Wiernik, +109 Additional Authors

Journal Articles

No abstract provided.

Targeted Mutational Profiling Of Peripheral T-Cell Lymphoma Not Otherwise Specified Highlights New Mechanisms In A Heterogeneous Pathogenesis., J. H. Schatz, S. M. Horwitz, J. Teruya-Feldstein, Matthew A. Lunning, A. Viale, K. Huberman, N. D. Socci, N. Lailler, A. Heguy, I. Dolgalev, J. C. Migliacci, M. Pirun, M. L. Palomba, D. M. Weinstock, H-G Wendel

Journal Articles: Oncology and Hematology

No abstract provided.

Selective Lymphadenectomy In Endometrial Cancer: Retrospective Analysis Of Morbidity And Survival Data At A Tertiary Care Centre, Uzma Chishti, Aliya Aziz, Munazza Akhtar, Sana Sheikh

Department of Obstetrics & Gynaecology

Objective: To compare perioperative morbidity and survival data between patients with early-stage endometrial cancer who did or did not undergo selective lymphadenectomy.
Methods: Retrospective analysis of 180 patients with early-stage endometrial carcinoma treated between 1999 and 2008 was performed in Aga Khan University Hospital, Karachi, Pakistan.
Results: Data from 180 patients were analysed. The selective lymphadenectomy group contained 108 women (60%) and the no lymphadenectomy group contained 72 women (40%). The median number of lymph nodes removed was 9. The mean age and extent of disease, as assessed by staging, tumour size, myometrial invasion, and lymphovascular invasion were comparable between …

Leishmania Donovani Bodies In Bone Marrow, Natasha Ali, Shabneez Hussain

Department of Pathology and Laboratory Medicine

We report a case of a 5-year-old female, resident of Afghanistan, who presented with fever and massive splenomegaly. Bone marrow revealed Leishmania donovani bodies (LD bodies) in macrophages characterized by a kinetoplast and characteristic double dot appearance. She was diagnosed as visceral leishmaniasis which is transmitted by sandflies (Phlebotomus).

Phase 2 Trial Of Cpx-351, A Fixed 5:1 Molar Ratio Of Cytarabine/Daunorubicin, Vs Cytarabine/Daunorubicin In Older Adults With Untreated Aml, J. E. Lancet, J. E. Cortes, D. E. Hogge, M. S. Tallman, T. J. Kovacsovics, L. E. Damon, R. Komrokji, S. R. Solomon, J. E. Kolitz, E. J. Feldman, +3 Additional Authors

Journal Articles

CPX-351 is a liposomal formulation of cytarabine: daunorubicin designed to deliver synergistic drug ratios to leukemia cells. In this phase 2 study, newly diagnosed older acute myeloid leukemia (AML) patients were randomized 2: 1 to first-line CPX-351 or 713 treatment. The goal was to determine efficacy and identify patient subgroups that may benefit from CPX-351 treatment. Response rate (complete remission 1 incomplete remission) was the primary end point, with event-free survival (EFS) and overall survival (OS) as secondary end points. The 126 patients entered were balanced for disease and patient-specific risk factors. Overall, CPX-351 produced higher response rates (66.7% vs …

Prognostic And Biologic Significance Of Dnmt3b Expression In Older Patients With Cytogenetically Normal Primary Acute Myeloid Leukemia, C. Niederwieser, J. Kohlschmidt, S. Volinia, S. P. Whitman, K. H. Metzeler, A. K. Eisfeld, K. Maharry, P. Yan, J. E. Kolitz, C. D. Bloomfield, +17 Additional Authors

Journal Articles

DNMT3B encodes a DNA methyltransferase implicated in aberrant epigenetic changes contributing to leukemogenesis. We tested whether DNMT3B expression, measured by NanoString nCounter assay, associates with outcome, gene and microRNA expression and DNA methylation profiles in 210 older (60 years) adults with primary, cytogenetically normal acute myeloid leukemia (CN-AML). Patients were dichotomized into high versus low expressers using median cut. Outcomes were assessed in the context of known CN-AML prognosticators. Gene and microRNA expression, and DNA methylation profiles were analyzed using microarrays and MethylCap-sequencing, respectively. High DNMT3B expressers had fewer complete remissions (CR; P=0.002) and shorter disease-free (DFS; P=0.02) and overall …

Prognostic Gene Mutations And Distinct Gene- And Microrna-Expression Signatures In Acute Myeloid Leukemia With A Sole Trisomy 8, H. Becker, K. Maharry, K. Mrozek, S. Volinia, A. K. Eisfeld, M. D. Radmacher, J. Kohlschmidt, K. H. Metzeler, J. E. Kolitz, C. D. Bloomfield, +14 Additional Authors

Journal Articles

No abstract provided.

Recombinant Interleukin-2 In Patients Aged Younger Than 60 Years With Acute Myeloid Leukemia In First Complete Remission, J. E. Kolitz, S. L. George, D. M. Benson, K. Maharry, G. Marcucci, R. Vij, B. L. Powell, S. L. Allen, D. J. Deangelo, Oncology Alliance Clinical Trials, +8 Additional Authors

Journal Articles

BACKGROUNDRecombinant interleukin-2 (rIL-2) induces cellular cytotoxicity against leukemia blasts. Patients with acute myeloid leukemia (AML) in first complete remission (CR) may harbor minimal residual disease that is susceptible to rIL-2-activated effector cells. METHODSIn the Cancer and Leukemia Group B (CALGB) 19808 study, patients with AML in first CR were randomly assigned after all planned chemotherapy to receive a 90-day course of subcutaneously administered rIL-2 or no further therapy. The primary objective was to compare disease-free survival (DFS) between the 2 treatment arms. A total of 534 patients achieved a CR, 214 of whom were randomized. Six courses of low-dose daily …

Validation Of Zap-70 Methylation And Its Relative Significance In Predicting Outcome In Chronic Lymphocytic Leukemia, R. Claus, D. M. Lucas, A. S. Ruppert, K. E. Williams, D. Weng, K. Patterson, M. Zucknick, J. C. Barrientos, K. R. Rai, J. C. Byrd, +13 Additional Authors

Journal Articles

ZAP-70 methylation 223 nucleotides downstream of transcription start (CpG+223) predicts outcome in chronic lymphocytic leukemia (CLL), but its impact relative to CD38 and ZAP-70 expression or immunoglobulin heavy chain variable region (IGHV) status is uncertain. Additionally, standardizing ZAP-70 expression analysis has been unsuccessful. CpG+223 methylation was quantitatively determined in 295 untreated CLL cases using MassARRAY. Impact on clinical outcome vs CD38 and ZAP-70 expression and IGHV status was evaluated. Cases with low methylation (0.90). Thus, ZAP-70 CpG+223 methylation represents a superior biomarker for TT and OS that can be feasibly measured, supporting its use in risk-stratifying CLL.

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.

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, …

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 …

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.

Thoracic Multidisciplinary Clinic (Tmdc) And The Treatment Of Stage Iii Non-Small Cell Lung Cancer, Eliot L. Friedman Md, Michael F. Szwerc Md, Robert Kruklitis Md, Michael J. Weiss

Department of Medicine

No abstract provided.

A 2-Step Approach To Myeloablative Haploidentical Stem Cell Transplantation With Optimized T-Cell Dosing: Early Immune Reconstitution Leads To Better Outcomes, Sameh Gaballa, Onder Alpdogan, Matthew Carabasi, Joanne Filicko, Margaret Kasner, Ubaldo E. Martinez-Outshoorn, Md, John L Wagner, Mark Weiss, Neal Flomenberg, Delores Grosso

Department of Medical Oncology Faculty Papers

We developed a 2-step approach to myeloablative haploidentical HSCT in which patients receive a large fixed dose of cyclophosphamide (CY)-tolerized T cells separately frm the HSC infusion in the hopes of accelerating post HSCT immune reconstitution (IR). The uniformity of the T cell dosing facilitates comparison of patients without (low risk) and with (high risk) active malignancy at HSCT to ascertain the impact of disease status at HSCT on IR with fewer confounding effects from conditioning or T cell dosing.

Frequency And Outcome Of Graft Versus Host Disease After Stem Cell Transplantation: A Six-Year Experience From A Tertiary Care Center In Pakistan, Natasha Ali, Salman Naseem Adil, Mohammad Usman Shaikh, Nehal Masood

Department of Pathology and Laboratory Medicine

Objective: The objective of this study was to evaluate the frequency and outcome of graft versus host disease after stem cell transplantation for various haematological disorders in Pakistan.
Materials and Methods: Pretransplant workup of the patient and donor was performed. Mobilization was done with G-CSF 300 mu g twice daily for five day. Standard GvHD prophylaxis was done with methotrexate 15mg/m(2) on day +1 followed by 10mg/m(2) on days +3 and +6 and cyclosporine. Grading was done according to the Glucksberg classification.
Results: A total of 153 transplants were done from April 2004 to December 2011. Out of these were …

The Use Of Infliximab To Control Recurrent Cytokine Storms In Ebv-Associated Angioimmunoblastic Lymphoma And Hemophagocytic Syndrome, Sameh Gaballa, Emmanuel Besa, Onder Alpdogan

Department of Medical Oncology Faculty Papers

Introduction: Chronic active Epstein-Barr virus infection (CAEBV) has been implicated in several diseases including hemophagocytic lymphohistiocytosis (EBV-HLH) and lymphomas including Angioimmunoblastic T cell lymphoma. The exact mechanism by which EBV infection causes these complications is currently not well understood. EBV-HLH is a syndrome in which T-cells, NK cells and macrophages are aberrantly activated. Cytokine storms play a major role in cellular damage and organ dysfunction. In the event that the body is unable to clear the EBV viremia, dysregulated T, NK cells and macrophages continue to release cytokines leading to the accumulation of lymphohistiocytic infiltrates into organs and organ damage. …

Allogeneic Stem Cell Transplantation In Acute Myeloid Leukemia, Natasha Bahadur Ali, Salman Adil, Mohammad Usman Shaikh, Nehal Masood

Department of Pathology and Laboratory Medicine

We report a case series of 12 patients with acute myeloid leukemia who underwent allogeneic stem cell transplant with a matched related donor. Male to female ratio was 1:1. The main complication post-transplant was graft-versus-host disease (n=7 patients). Transplant-related mortality involved one patient; cause of death was multi-organ failure. After a median follow up of 36.0±11.3 months, overall survival was 16%.

Sickle Cell Pain: A Critical Reappraisal., Samir K. Ballas, Kalpna Gupta, Patricia Adams-Graves

Department of Medicine Faculty Papers

Sickle cell pain includes 3 types: acute recurrent painful crises, chronic pain syndromes, and neuropathic pain. The acute painful crisis is the hallmark of the disease and the most common cause of hospitalization and treatment in the emergency department. It evolves through 4 phases: prodromal, initial, established, and resolving. Each acute painful episode is associated with inflammation that worsens with recurrent episodes, often culminating in serious complications and organ damage, such as acute chest syndrome, multiorgan failure, and sudden death. Three pathophysiologic events operate in unison during the prodromal phase of the crisis: vaso-occlusion, inflammation, and nociception. Aborting the acute …