Myeloid Leukemia – Clinical Diagnosis and Treatment

Published in Downloads
Monday, 10 April 2017 22:09

Description: This book comprises a series of chapters from experts in the field of diagnosis and treatment of myeloid leukemias from all over the world, including America, Europe, Africa and Asia. It contains both reviews on clinical aspects of acute (AML) and chronic myeloid leukemias (CML) and original publications covering specific clinical aspects of these important diseases.

Covering the specifics of myeloid leukemia epidemiology, diagnosis, risk stratification and management by authors from different parts of the world, this book will be of interest to experienced hematologists as well as physicians in training and students from all around the globe. Covering the specifics of myeloid leukemia epidemiology, diagnosis, risk stratification and management by authors from different parts of the world, this book will be of interest to experienced hematologists as well as physicians in training and students from all around the globe.

Incidental finding of 3 Southeast Asian ovalocytosis cases by attentive examination of blood smears

Published in Microbiology
Saturday, 04 March 2017 17:08

A 52-year-old Malaysian man, a 24-year-old sub-Saharan woman, and a 28-year-old Madagascan woman (who was heterozygous for hemoglobin S) were admitted to North Hospital in Marseilles, France. Blood tests using an Advia2120i hematology analyzer (Siemens) showed no or mild anemia (109-150 g/L), normal or high mean corpuscular hemoglobin concentration (339-364 g/L), and borderline or slightly high red cell distribution width (15%-19.2%).

The red blood cell (RBC) volume and hemoglobin concentration cytogram clearly showed a typical distribution of comma-shaped RBCs, with an increased number of hyperchromic RBCs (panel A). Examination of the blood smear revealed anisocytosis and poikilocytosis, without spherocytes but with ovalocytes and macro-ovalocytes, some of them with more than 1 ridge (panel B; original magnification ×100, May-Grünwald Giemsa stain). The eosin-5′-maleimide binding test performed for each patient showed a reduced mean channel fluorescence between 26.2% and 30.9%, confirming an anomaly of the band-3 protein. A heterozygous 9-amino-acid deletion (residues 400 to 408) in band 3 (SLC4A1), which is the most common genetic abnormality in Southeast Asian ovalocytosis (SAO), was found in all 3 patients. Most cases of SAO are asymptomatic, so careful examination of a cytogram from the Advia2120i analyzer and close observation of the blood smear can help diagnose SAO.

How do you die from multiple myeloma?

Published in Immunology
Tuesday, 18 October 2016 16:17

Multiple Myeloma: Early Death Common and Preventable

Improved survival among patients with multiple myeloma is one of the most impressive cancer treatment success stories in recent years.

A decade ago, patients survived an average 3 to 4 years following a multiple myeloma (MM) diagnosis, but median survival times have doubled and continue to improve, said multiple myeloma researcher Shaji Kumar, MD, of Mayo Clinic, Rochester, Minnesota.

This is due largely to the introduction of novel biologic therapies and greater use of autologous stem cell transplant. While there is still no cure for the neoplastic plasma-cell disorder, these treatments now routinely prolong initial remission and survival.

Early death remains common

Considered a rapidly fatal disease just a decade ago, MM is now considered more of a chronic condition for many, but not all, patients, Kumar said in a telephone interview.

Early death remains a significant and under-recognized problem in multiple myeloma, especially among patients with serious comorbidities or those who are very old. These patients often do not receive today’s gold-standard treatments, and that is a problem, Kumar said.

“About a quarter of patients will die within the first 2 to 3 years of diagnosis, for a number of reasons,” Kumar said, adding that he believes early mortality among multiple myeloma patients could be reduced by a third or even half if strategies to identify and treat those most at-risk were systematically applied.”

“Do’s and Don’ts” in early treatment

These strategies were outlined by Kumar and colleagues from Mayo Clinic and the University of Alabama at Birmingham in a recent analysis, published ahead of print by the American Journal of Hematology.

“Multiple myeloma is not a rare disease, but it is not commonly seen by oncologists in general practice,” analysis co-author Luciano J. Costa, MD, of the University of Alabama at Birmingham said. “Some may see only 1 or 2 of these patients a year, so we felt it was important to highlight some key strategies for reducing early death rates in this population.”

In a separate population analysis of 30,324 multiple myeloma patients published late in 2014, Kumar, Costa and colleagues found that while early mortality–defined as death within a year of MM diagnosis–has decreased over time, it still occurred in 28.6% of patients diagnosed in the U.S. between 1993 and 2010.

The incidence of early death among patients diagnosed before the age of 65 was 17.6% and incidence among older patients was 35.3%.

Majority of MM patients are age 65+

“About two-thirds of patients are 65 or older when diagnosed, so this at-risk group represents the overwhelming majority of patients,” Costa said. “And most of these older patients are not dying from refractory disease.”

Instead, Costa said he believes many die because they are either not getting optimal therapies or because they are very ill from co-morbid diseases at the time of their diagnoses.

These very ill or elderly patients have typically been excluded from multiple myeloma clinical trials, so there is little to guide physicians treating them.

This is why careful risk stratification and identification of co-morbidities immediately following a MM diagnosis is critical, Kumar noted.

“We need to manage the myeloma in the context of the other things going on with the patient,” he said.

The strategy for managing newly diagnosed MM outlined by Costa, Kumar and colleagues included a series of “do’s” and “don’ts” derived from their experience treating patients with the bone marrow cancer. Their aim was not to present comprehensive recommendations for treatment, but, instead, to focus on strategies designed to avoid early complications and death.

Among the recommended “do’s” and “don’ts”:

Do institute prompt systemic therapy

The researchers’ 2014 analysis revealed that the risk of early death was higher when novel MM drugs were not used as part of treatment.

While physicians may be tempted to focus on supportive care for conditions that accompany MM, such as hypercalcemia, bone lesions, renal failure and anemia, the researchers wrote that these treatments should not replace systemic therapy.

“It is crucial to keep in mind that ultimate symptom control or reversal of complication can only be obtained with systemic treatment, and none of the supportive measures above precludes prompt initiation of systemic therapy,” they wrote.

Do treat hypercalcemia aggressively

Approximately 1 in 5 patients develop hypercalcemia, resulting from increased activation of osteoclasts. The researchers noted that the “prompt and effective management of hypercalcemia is imperative to prevent early mortality in newly diagnosed MM.”

They added that in cases of mild hypercalcemia, aggressive rehydration with normal saline along with corticosteroids should suffice, as long as hydration is carefully monitored to avoid congestive heart failure.

In moderate to severe cases (serum calcium >12 mg/dL), an ECG is recommended to rule out arrhythmias. In addition to hydration and corticosteroids, the researchers recommended anti-bone resorption therapies, and they noted that results from two separate trials in patients with malignancy-related hypercalcemia found zoledronic acid to be superior to pamidronate for normalizing calcium levels.

Drugs that cause hypercalcemia should also be avoided, as well as drugs that can worsen neurological status in the setting of concurrent hypercalcemia, “to allow adequate assessment of neurological status.”

Do avoid and manage infections

Infections are the most common cause of early death in MM patients. One study found that 45% of deaths within 2 months of diagnosis were associated with infections. A population-based study from Sweden showed a 7- to 10-fold increase in bacterial and viral infection risk in MM patients, compared to the general population.

The use of prophylactic antibiotics to prevent infections in MM remains controversial, and the researchers noted that routine prophylaxis is not advised. They did, however, recommend the use of TMP-SMX to prevent fungal pneumonias in patients treated with 20 mg/d or more of prednisone. They also recommended prophylactic use of acyclovir or valacyclovir for patients receiving proteasome inhibitors (PIs) that disrupt normal T-cell immunity.

“For all patients receiving bortezomib and for that matter even newer PIs such as carfilzomib, we recommend administering antiviral prophylaxis with acyclovir 400 mg twice daily or valacyclovir 500 mg once a day,” they wrote.

Do avoid thromboembolic events (VTE)

This risk increases with age, and patients with blood cancers such as MM have an especially high risk for clot-related events. The researchers recommend educating all newly diagnosed patients on the warning signs for the development of VTEs. They also recommend the use of VTE prophylaxis in all newly diagnosis MM patients receiving IMiD-immunomodulator therapies.

“In MM patients who develop a thrombosis upon initiating treatment, it is reasonable to hold their treatment and resume after they are therapeutically anticoagulated,” the researchers wrote. “This level of anticoagulation may be continued for the remainder of the duration of MM-directed therapy as long as the risk of serious bleeding complications is deemed acceptable.”

Remaining “do’s” and “don’ts” recommended in the analysis included:

  • Do address comorbidities and manage pain.
  • Don’t postpone systemic therapy to address localized lesions.
  • Don’t administer prolonged courses of high-dose corticosteroids.
  • Don’t change well-tolerated therapy due to perceived suboptimal response if clinical benefit is shown.
  • Don’t administer radiation when symptoms can be managed with systemic therapy.
  • Don’t administer inferior treatment solely based on advanced age of performance status.

“In recent years we have seen an explosion in the number of available therapies for multiple myeloma, but older, sicker patients may not be getting these treatments,” Costa said. “Since about two-thirds of newly diagnosed patients are age 65 or older, it is important to address the issue of suboptimal treatment in this population.”


By Salynn Boyles
Reviewed by Alan S. Weinstein, MD, FACP, Medical Director (retired), Virtua Fox Chase Cancer Program, Marlton, NJ


Source: MEDPAGE TODAY: Multiple Myeloma: Early Death Common and Preventable

Multiple Myeloma – An Overview

Published in Downloads
Tuesday, 18 October 2016 16:08
Description: Multiple myeloma is a malignant disorder characterized by the proliferation of plasma cells. Much insight has been gained into the molecular pathways that lead to myeloma and indeed much more remains to be done. The understanding of these pathways is closely linked to their therapeutic implications and is stressed upon in the initial chapters.

Recently, the introduction of newer agents such as bortezomib, lenalidomide, thalidomide, liposomal doxorubicin, etc. has led to a flurry of trials aimed at testing various combinations in order to improve survival. Higher response rates observed with these agents have led to their integration into induction therapies. The role of various new therapies vis a vis transplantation has also been examined. Recent advances in the management of plasmacytomas , renal dysfunction, dentistry as well as mobilization of stem cells in the context of myeloma have also found exclusive mention. Since brevity is the soul of wit our attempt has been to present before the reader a comprehensive yet brief text on this important subject.

Multiple Myeloma – A New Era of Treatment Strategies

Published in Downloads
Tuesday, 18 October 2016 15:08
Description: Multiple Myeloma (MM), the second most common blood cancer in adults, is a clonal plasma cell malignancy within the bone marrow characterized by osteolytic bone lesions, renal disease, and immunodeficiency. It is now well established that MM cell- induced disruption of the bone marrow homeostasis between the highly organized cellular and extracellular compartments supports MM cell proliferation, survival, migration, and drug resistance via activation of various signaling pathways. Based on this knowledge, the prototypic drugs thalidomide, bortezomib, and lenalidomide, which target both MM cells and the bone marrow microenvironment, have already fundamentally changed treatment options of this disease. Indeed, their benefit is now not only shown in relapsed and refractory disease but they also improve overall response, duration of response, and progression-free and overall survival when used as part of first-line regimens. However, despite new insights into MM pathogenesis and exciting derived therapeutic advances, MM still remains incurable. Ongoing studies are therefore aiming to further delineate mechanisms of MM pathogenesis within the bone marrow to identify novel agents with enhanced cytotoxicity and decreased drug resistance to improve patient outcome.
 
Multiple Myeloma - A New Era of Treatment Strategies is devoted to contributions from eminent scientists providing readers with comprehensive accounts of the most recent developments in the field of MM research. It addresses the interests of scientists and clinical investigators in MM research as well as other fields of oncology, in which the microenvironment is believed to play an important role.

Cancer Imaging: Lung and Breast Carcinomas

Published in Downloads
Saturday, 14 May 2016 11:01
Description: With cancer-related deaths projected to rise to 10.3 million people by 2020, the need to prevent, diagnose, and cure cancer is greater than ever. This book presents readers with the most up-to-date imaging instrumentation, general and diagnostic applications for various cancers, with an emphasis on lung and breast carcinomas--the two major worldwide malignancy types. This book discusses the various imaging techniques used to locate and diagnose tumors, including ultrasound, X-ray, color Doppler sonography, PET, CT, PET/CT, MRI, SPECT, diffusion tensor imaging, dynamic infrared imaging, and magnetic resonance spectroscopy. It also details strategies for imaging cancer, emphasizing the importance of the use of this technology for clinical diagnosis. Imaging techniques that predict the malignant potential of cancers, response to chemotherapy and other treatments, recurrence, and prognosis are also detailed.
  • Concentrates on the application of imaging technology to the diagnosis and prognosis of lung and breast carcinomas, the two major worldwide malignancies 
  • Addresses the relationship between radiation dose and image quality
  • Discusses the role of molecular imaging in identifying changes for the emergence and progression of cancer at the cellular and/or molecular levels

Advances in Cancer Research, Volume 84

Published in Downloads
Saturday, 07 May 2016 10:24
Description: The Advances in Cancer Research series provides invaluable information on the exciting and fast-moving field of cancer research. This volume presents outstanding and original reviews on a variety of topics, including gene expression in inherited breast cancer, multiparameter analyses of cell cycle regulation in tumorigenesis, Rho GTPases in transformation and metastasis, the myc oncogene, genetic requirements for the episomal maintenance of oncogenic herpesvirus genomes, treatment of Epstein-Barr virus-associated malignancies with specific T cells, the role of glycogen synthase kinase-3 in cancer, chronic immune activation and inflammation in the pathogenesis of AIDS and cancer, and molecular biology of Hodgkin's lymphoma.
  • Gene Expression in Inherited Breast Cancer 
  • Multiparameter Analyses of CellCycle Regulatory Proteins in Human Breast Cancer: A Key to Definition of Separate Pathways in Tumorigenesis
  • Rho GTPases in Transformation and Metastasis
  • The myc Oncogene: Marvelously Complex
  • Genetic Requirements for the Episomal Maintenance of Oncogenic Herpevirus Genomes
  • Treatment of Epstein-Barr Virus-Associated Malignancies with Specific T Cells
  • Role of Glycogen Synthase Kinase-3 in Cancer: Regulation Wnts and Other Signaling Pathways
  • Chronic Immune Activation and Inflammation in the Pathogenesis of AIDS and Cancer
  • Molecular Biology of Hodgkin's Lymphoma

Breast Cancer - Contemporary Issues in Cancer Imaging

Published in Downloads
Tuesday, 26 April 2016 00:38
Description: Worldwide, breast cancer is by far the most common cancer amongst women, with an incidence rate more than twice that of colorectal cancer and cervical cancer and about three times that of lung cancer. Whilst screening programmes have improved detection, this disease still places a very high burden on healthcare services worldwide. Over the last two decades, improved public awareness, the implementation of population screening by mammography, and the development of new technology for diagnosis have transformed the care of patients with breast cancer. In this volume, recognised experts discuss key current issues in the diagnosis and management of breast disease. The development and application of new diagnostic techniques is described as well as the use of sophisticated drugs for more effective treatment. Complex contentious topics including risk factors, borderline lesions, professional performance and quality assurance are thoroughly explored by an expert multidisciplinary team.

25 Years of p53 Research - 2007

Published in Downloads
Monday, 25 April 2016 02:51
Description: p53 has emerged as a key tumor suppressor and important target for novel cancer therapy. This book, written by world-leading p53 researchers including many of those who have shaped the field over the past 25 years, provides unique insights into the progress of the field and the prospects for better cancer diagnosis and therapy in the future.

Diagnostic Pediatric Hematopathology 2011

Published in Downloads
Monday, 25 April 2016 02:05
Description: Diagnostic Pediatric Hematopathology is unique in providing an accurate and up-to-date guide to the diagnosis of benign and malignant hematologic disorders of childhood. The text discusses the development of the hematopoietic and lymphoid systems - and how this affects normal and abnormal findings in children at various ages. Also examined are the morphologic, immunophenotypic, cytogenetic, and molecular genetic characteristics of most pediatric-specific hematologic diseases. This is an excellent reference that ensures accurate diagnoses when evaluating peripheral blood, bone marrow, and lymph nodes of children. The text is written by a team of experienced pediatric hematopathologists and clinical scientists drawn from major academic children's hospitals in the United States, United Kingdom, and Canada. It will be a valuable tool in the every day practice of pathologists, pediatric pathologists, and hematopathologists, and a ready educational resource for fellows, pathology residents, medical students, clinical scientists in the field, and pediatric hematologists/oncologists.
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