The Hematologist

March April 2011 Vol 8 Issue 2

March-April 2011, Volume 8, Issue 2

Features

  • Enhancing Research in Regenerative MedicineMarch 01, 2011

    Over the past decade regenerative medicine has become a highly active area of investigation with the potential to address many unmet medical needs. Hematologists have played a prominent role in advancing this emerging field because of prior expertise in stem cell and transplantation biology as well as extensive experience in related areas of translational research. Despite the impetus for growth this field has experienced, investigators continue to face numerous challenges in conducting translational and clinical research in regenerative medicine and cell-based therapy.

     

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Diffusion

  • A Role for TET2 Dysregulation in Myeloid MalignanciesMarch 01, 2011 | Steven Grant, MD

    Aberrant methylation of DNA, particularly hypermethylation of tumor suppressor genes, occurs frequently in many cancers, including hematopoietic malignancies. This has prompted the development of agents capable of reversing hypermethylation, such as DNA methyltransferase inhibitors. These agents have yielded encouraging results both alone and in combination with other epigenetic agents (e.g., histone deacetlyase inhibitors) in patients with myelodysplastic syndrome (MDS) and some acute leukemias.

  • Antiphospholipid Antibodies Do NO WrongMarch 01, 2011 | Robert Flaumenhaft, MD, PhD

    The underlying molecular events responsible for antiphospholipid antibody syndrome (APS) have been difficult to pinpoint. Characterization of causative antibodies has demonstrated that they are not actually directed at phospholipids, but rather directed at plasma proteins that bind phospholipids. β2-glycoprotein I (β2-GPI) is an important antigen in this regard, but despite its high plasma concentration and central role in APS, the function of β2-GPI in normal physiology remains poorly defined. 

  • Clinical Anti-Myeloma Activity of AminobisphosphonatesMarch 01, 2011 | Kenneth C. Anderson, MD

    Bisphosphonates have demonstrated an ability to reduce skeletal-related events (SRE), including bone pain, pathologic fracture, spinal cord compression, and need for radiation to bone. As approximately 80 percent of patients with multiple myeloma (MM) have bone disease, the use of bisphosphonates has transformed the paradigm for supportive care in MM.

  • CT Scans in Response and Follow-Up Assessment of CLL: Can We Eliminate Their Use?March 01, 2011 | John C. Byrd, MD

    Chronic lymphocytic leukemia (CLL) is a disease characterized by blood lymphocytosis, cytopenias, bone marrow infiltration, lymph node enlargement, and hepatosplenomegaly. Prior to the availability of modern imaging studies, the Rai or Binet Staging systems employed a routine blood test and physical exam to predict patient outcomes at diagnosis. 

  • Gene Therapy for Wiskott-Aldrich Syndrome: Benefits and RisksMarch 01, 2011 | Diane Krause, MD, PhD

    An international team headed by Dr. Christoph Klein in Germany has reported clinical improvement after gene therapy in two children with Wiskott-Aldrich Syndrome (WAS), a disease caused by mutation of the gene encoding Wiskott Aldrich syndrome protein (WASp). In patients with this condition, the lack of functional WASp, which plays a critical role in actin polymerization in blood cells, leads to thrombocytopenia as well as immunodeficiency with recurrent infections and a tendency toward development of autoimmune diseases. 

  • Is There a Path to Quality of Life for Elderly Patients Treated for Myeloma?March 01, 2011 | Xavier Leleu, MD, PhD

    The treatment of elderly patients with newly diagnosed symptomatic multiple myeloma has improved since the era of melphalan plus prednisone, the standard treatment for more than 30 years. Current regimens still include melphalan plus prednisone as a backbone for combination regimens that contain newer agents, such as bortezomib, lenalidomide, or thalidomide therapy. Despite remarkable response rates and survival benefits, none of these combinations has freed patients and physicians from the anxiety of various side effects. Aside from constipation and somnolence, thalidomide shares thromboembolic events and fatigue with lenalidomide, and peripheral neuropathy with bortezomib.

  • Membrane Phospholipid Scrambling by TMEM16FMarch 01, 2011 | Pete Lollar, MD

    The plasma membrane of animal cells contains a phospholipid bilayer; the outer leaflet largely contains phosphatidylcholine and sphingomyelin and the inner leaflet is mainly composed of phosphatidylserine (PS) and phosphatidylethanolamine (PE). This lipid asymmetry is maintained by an ATP-dependent enzyme called the aminophospholipid translocase.

  • Not Too Little, Not Too Much, Just the Right Amount of Hepcidin Can Limit Iron Overload in β-Thalassemic MiceMarch 01, 2011 | Gregory M. Vercellotti, MD

    Remarkable advances in the care of β-thalassemic patients over the past 40 years have prolonged lives and prevented organ dysfunction due to iron overload through the use of parenteral and oral iron chelators. Iron overload occurs in β-thalassemia because ineffective erythropoiesis and frequent RBC transfusions over-enhance iron absorption.  

  • Take This One for a Test Drive: It Looks Like a HITMarch 01, 2011 | Margaret V. Ragni, MD, MPH

    Heparin-induced thrombocytopenia (HIT) is a thrombotic disorder, occurring in 3 percent or more of individuals exposed to heparin, in which antibodies to platelet factor 4-glycosaminoglycan complexes form on platelet surfaces, leading to thrombi, which can be life-threatening. Diagnosis of this disorder can be difficult because the clinical picture may be confusing and assays are limited by poor specificity and lack of availability in real time.

     

  • The Flavors of MPNs: Is STAT1 the Key Ingredient?March 01, 2011 | Jason Gotlib, MD, MS

    The Flavors of MPNs Is STAT1 the Key Ingredient?Dr. Gotlib indicated no relevant conflicts of interest. Chen E, Beer PA, Godfrey AL, et al. Distinct clinical phenotypes associated with JAK2V617F reflect differential STAT 1 signaling. Cancer Cell. 2010 18 524

  • Turning Over the Rotting Log in Del(5q) MyelodysplasiaMarch 01, 2011 | David P. Steensma, MD

    The immunomodulatory drug lenalidomide can induce striking hematologic and cytogenetic responses in patients with myelodysplastic syndromes (MDS), especially among patients whose clonal cells bear a somatic deletion of the long arm of chromosome 5q (del(5q)). Unfortunately, most patients whose cytopenias and burden of clonal cells improve during lenalidomide therapy will relapse within three years - including the approximately 45 percent of patients with lower-risk del(5q) MDS who achieve a complete cytogenetic remission.

     

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Ask the Hematologist

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Mini Review

  • Dabigatran: An Important New Option for Chronic AnticoagulationMarch 01, 2011 | Lawrence Leung, MD

    It is well known to hematologists that managing patients who require chronic anticoagulation is a cumbersome task, and until very recently, warfarin, a vitamin K antagonist, has been the only available oral anticoagulant. Warfarin treatment requires regular monitoring with prothrombin time testing, and, since it has multiple interactions with food and drugs, frequent dose adjustments are necessary. Despite regular monitoring by either patient self-management or hospital-based anticoagulation clinics, patients fall outside the desired therapeutic range about one-third of the time. So the recent FDA approval of the orally active direct thrombin inhibitor (DTI) dabigatran etexilate has been welcome news.

     

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Clinical Trials Corner

  • Polycythemia VeraMarch 01, 2011

    Bart Scott, MD, and Michael Linenberger, MD 2011 03 01Dr. Scott is the local site investigator for this trial at the University of Washington Medical Center. Study Title Randomized, Open Label, Multicenter Phase III Study of Efficacy and Safety in

  • Transfusion Independence in MDS Patients Treated with LenalidomideMarch 01, 2011 | David P. Steensma, MD

    David P. Steensma, MD2011 03 01Study Title A Study of Lenalidomide Versus Placebo in Subjects With Transfusion Dependent Anemia in Low Risk Myelodysplastic Syndrome (MDS) Without Del 5Q (MDS 005) Coordinator The study is sponsored by Celgene, the manufacturer of

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Profiles

  • Eugene Goldwasser 1922 – 2010March 01, 2011

    ASH Emeritus member Eugene Goldwasser, PhD, of the University of Chicago, died on December 17, 2010, at his home in Chicago, IL, of complications of prostate cancer. He was 88. 

  • The ASH Scholar Award: Just the BeginningMarch 01, 2011 | David Motto, MD, PhD

    The day I received the e-mail informing me that I was a recipient of the 2005 ASH Scholar Awards for fellows is fondly and forever etched in my memory. At the time, I was a postdoctoral fellow in David Ginsburg's laboratory at the University of Michigan. We were just about to begin the practice session for our upcoming platform presentations at the ASH annual meeting, which was in San Diego that year, and just around the corner. I quickly printed the critiques, went downstairs to the conference room, and read them with a big smile on my face as everyone filtered in and got their lunches. 

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President's Column

  • President’s Column: Restoring Clinical and Translational ResearchMarch 01, 2011 | J. Evan Sadler, MD, PhD

    Recent advances in basic and translational research have set the stage for tremendous progress in clinical hematology research, but trials to pursue these opportunities run afoul of many obstacles. For example, David Dilts, Director of Clinical Research of the Knight Cancer Institute, reported last year that opening a phase III cooperative oncology group trial requires an average of 2.5 years to accommodate 118 decision points, complete more than 769 process steps, and receive approval by up to 36 separate groups or individuals. Whether many of these steps improve trial quality or patient safety is doubtful. 

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Op-Ed

  • The Perpetual Fellow — Extending Fellowship Training in Hematology: The Trainee PerspectiveMarch 01, 2011

    Current trainees wishing to pursue an academic career feel increasing pressure to obtain additional clinical and research training beyond their hematology/oncology fellowship in the form of "fourth-year options," additional fellowships, or advanced degrees. Trainees also face rising debts from medical education and the need to support their families, while shouldering the cost of caring for their aging parents, following in the footsteps of the "sandwich generation." Increasing financial constraints, prolonged training, reduced grant funding, delayed retirement savings, and deferred investment opportunities can greatly affect a hematology/oncology fellow's career choices and could potentially drive fellows out of academics.

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Letters to the Editor

  • Letter to the EditorMarch 01, 2011

    Dr. DiMichele outlined the appropriate evaluation that should be performed at presentation. She also gave sound counsel concerning the young woman's request for combined hormonal oral contraceptive pills, an effective treatment for menorrhagia, but complicated in this patient by the family history of thrombophilia. The wise advice here was avoidance of risk factors. The comprehensive nature of Dr. DiMichele's reply is evidenced in her noting the importance of the psychosocial, or quality-of-life, consequences for adolescents who must face these issues.

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News and Reports

  • ASH Program Successful in Promoting Minority CareersMarch 01, 2011 | Michael DeBaun, MD, MPH

    Five years ago, ASH entered into a partnership with the Harold Amos Medical Faculty Development Program (AMFDP) of the Robert Wood Johnson Foundation in an effort to increase the number of underrepresented minority scholars receiving academic and research appointments in the field of hematology. Although the AMFDP has been supporting minority scholars for more than 25 years, ASH’s funding of the joint ASH-AMFDP Award helps to ensure that deserving applicants in the field of hematology receive the support they need. Since the new award was launched in 2006, five scholars, one per year, have been accepted into the program, which is a remarkable accomplishment considering that the AMFDP accepts applications from all specialties and funds only eight to 12 scholars per year.

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