Tag Archives: Hematology/Oncology

Big News in the Field of Cancer!

At this year’s American Society of Clinical Oncology (ASCO) conference in Chicago recently, there were a lot of presentations on immunotherapy to treat cancer and tailoring therapies for individuals based on genetic mutations. Abstracts from the conference were recently published on ASCO’s website. The National Cancer Institute announced on Monday plans to launch a national research study sorting cancer patients to treatment groups based on genetic mutations rather than cancer type. This study could lead to drug trials that can be implemented more quickly and possibly match patients with a better suited drug for their cancer. These newer designed studies are referred to as “basket trials”. Click on the link below to a interesting graphic from the Washington Post that illustrates the difference between conventional clinical trials and basket trials.

A Novel Way to Target Cancer and its Treatments (Washington Post)

HIT(T): Duration of Anticoagulation

  • Bilateral lower extremity compression ultrasonography may be considered in patients with HIT, whether or not there is clinical evidence of lower-limb DVT, because silent DVT is common and its presence may influence the recommended duration of anticoagulation.
  • For patients with HIT-associated thrombosis (i.e. HITT), anticoagulate for a defined course (typically 3 months) as with other provoked thromboses.
  • For patients with HIT without thrombosis (i.e. isolated HIT), the optimal duration of anticoagulation is unknown. Because there is an elevated risk of thrombosis extending 2 to 4 weeks after heparin is stopped, anticoagulation for up to 4 weeks should be considered.
  • For all patients, anticoagulation management should be based on an individualized risk/benefit assessment.

Polycythemia Vera

  • General Information
    • Polycythemia
      • Defined as increase in # RBC in the peripheral blood
      • Men Hgb >18.5 or Hct >52
      • Women Hgb > 16/5 or Hct >48
    • Relative polycythemia
      • A decrease in plasma volume that elevates the Hct or Hgb
    • Absolute polycythemia
      • Primary – mutations such as polycythemia vera, idiopathic familial polycythemia, EPO R gene mutations
      • Secondary – chronic hypoxia (high altitude, smoking, cardiac shunts, pulmonary disease, sleep apnea, EPO producing tumors (RCC, HCC, pheo, uterine fibroids), other (use of EPO injection, steroids, blood doping)
  • Symptoms
    • Indicating the hyperviscosity: chest pain, abd pain, HA, change in vision or mentation
    • Indicating polycythemia vera: post bath pruritis, erthromelalgia, gout , arterial or venous thromboses
  • Diagnosis
    • Repeat testing to avoid testing transient increases
    • History and physical considering the prior diagnoses listed, the most common cause of polycythemia is hypoxia 2/2 pulmonary disease
    • Pulse ox and ABG, CBC, UA, LFTs, CXR
    • If etiology is unclear, consider checking EPO and JAKPCV
  • Management
    • Phlebotomy: often to a goal hct below 45 for men or 42 for women.
    • Low dose ASA to reduce thrombotic complications
    • Cytoreductive therapy: i.e. hydroxyurea
    • Other therapies:
      • Interferon
      • Anagrelide (inhibits platelet maturation): PCV with secondary thrombocytosis
      • Erlotinib
      • Selective JAK2 inhibitors are being investigated

UTSW Intern Publications!

Dr. Arjun Gupta (PGY-01) has published several studies and case reports this year. Click on the links below to read his work! Great job Arjun!

The Impact of Physician Posture During Oncology Patient Encounters

An Unusual Cause of Facial Rash

Everything Points to Myeloma 

Altered mental status: what is the diagnosis?

MYST3/CREBBP Rearranged Acute Myeloid Leukemia after Adjuvant Chemotherapy for Breast Cancer

Long-term outcome of pyogenic vertebral osteomyelitis: a cohort study of 260 patients. 

Atrial Myxoma

General Information
  • Most common primary cardiac neoplasm
  • Prevalence of cardiac tumors at autopsy ranges from 0.001% to 0.3%
  • Thought to originate from entrapped entrapped embryonic foregut
  • Histologically, composed of scattered cells within a mucopolysaccharide stroma
  • Produce VEGF, which contributes to the induction of angiogenesis and the early stages of tumor growth
  • On a macroscopic level, typical myxomas are pedunculated and gelatinous in consistency; the surface may be smooth, villous, or friable.
  • 35 percent of myxomas are friable or villous, and these tend to present with emboli.
Clinical Manifestations
  • Symptoms:
    • Due to obstruction of blood flow, valvular regurgitation, impaired contractility
    • Can see dyspnea, orthopnea, paroxysmal nocturnal dyspnea, pulmonary edema, cough, hemoptysis, edema, and fatigue
    • Direct invasion of myocardium can cause arrhythmias, heart block, or pericardial effusion with or without tamponade
    • Left atrial tumors may release tumor fragments or thrombi into the systemic circulation, leading to embolization in multiple vascular territories
    • May be worse in certain body positions, due to motion of the tumor within the atrium
  • Signs:
    • On physical examination, a characteristic “tumor plop” may be heard early in diastole.
    • Constitutional symptoms (e.g., fever, weight loss) are seen in around 30 percent of patients.
    • Laboratory abnormalities (e.g., anemia and elevations in the ESR or CRP) are present in 35 percent, usually those with systemic symptoms].

 

Diagnostic Evaluation 
  • Echocardiography
    • Images both the myocardium and the cardiac chambers can usually identify the presence of a mass
    • In addition, echocardiography may provide information about any obstruction to the circulation, as well as the likelihood that the tumor could be a source of emboli
    • TTE is sufficient, but TEE may be better. The superior diagnostic utility of TEE is due to the proximity of the esophagus to the heart, the lack of intervening lung and bone, and the ability to use high-frequency imaging transducers that afford superior spatial resolution.
  • Cardiac MRI and Computerized Tomography
    • MRI is preferred. In addition to furnishing detailed anatomic images, the T1- and T2-weighted sequences reflect the chemical microenvironment within a tumor, thereby offering clues as to the type of tumor that is present.
    • However, CT scanning is still useful when MRI is not immediately available or is contraindicated.
  • PET scan
    • Useful in identifying cardiac involvement in patients with metastatic tumors, atrial myxoma or lipomatous septal hypertrophy.
  • Transvenous biopsy
    • Limited data is available on the risks and benefits of transvenous biopsy of suspected cardiac tumors.
    • Because myxomas may embolize, transvenous biopsy is not generally warranted if the appearance is typical on noninvasive imaging.
    • Biopsy is considered reasonable for other cardiac tumors if potential benefits are deemed sufficient to outweigh potential risks.

 

Treatment and Prognosis

 

  • Once a presumptive diagnosis of myxoma has been made on imaging studies, prompt resection is required because of the risk of embolization or cardiovascular complications, including sudden death.
  • The results of surgical resection are generally very good, with most series reporting an operative mortality rate under 5 percent.
  • Postoperative recovery is generally rapid.
  • Atrial arrhythmias or atrioventricular conduction abnormalities were present postoperatively in about 25% of patients
  • Approximately 5% risk for recurrence, suggesting the need for careful follow-up

Adapted from: Cohen et al. Atrial Myxoma: A Case Presentation and Review.Cardiology Research. 3 (1), 2012, 41-44. CC BY-SA 4.0

 

Answer to CC #9

Case Challenge #9 presented a 52 year old female with fever, new-onset weakness, and dyspnea on exertion associated with weight loss and a rash. She is afebrile, has petechiae on her fingertips, left-sided weakness. Heart sounds reveal a CARDIAC “PLOP.” MRI reveals multifocal acute CVA in different vascular distributions.

What is the most likely diagnosis?

  • Coxiella endocarditis
  • Hereditary hemorrhagic telangiectasia
  • Whipple’s disease
  • Rheumatic fever
  • Atrial myxoma

The patient has evidence of embolic disease, presumably from a cardiac source, as evidenced by the multifocal acute CVA. The key finding here is in the heart sounds. The atrial myxoma produces a diastolic sound that is referred to as a “tumor plop.” This sound arises from obstruction to ventricular in-flow that occurs as the tumor comes to rest over the mitral annulus. For more information, click the image below to hear a short podcast about atrial myxoma and the tumor plop.

LAMyxomaDiagram

 

Thrombotic Thrombocytopenic Purpura (TTP)

General Information

TTP is a rare hematologic emergency in which various organs, mainly the brain and kidneys, are affected by ischemic damage due to platelet aggregation. Advances in our understanding of the molecular pathology led to the recognition of three different diseases: typical HUS caused by Shiga toxin-producing Escherichia coli (STEC-HUS); atypical HUS (aHUS), associated with genetic or acquired disorders of regulatory components of the complement system; and TTP that results from a deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor.  TTP may be congenital or acquired as a result of HIV, connective tissue disorder, cancers, drugs like quinine, mitomycin C, cyclosporine, oral contraceptives, and ticlopidine or it may be idiopathic. 


Clinical Manifestations (i.e. the PENTAD!)

It is characterized by thrombocytopenia, microangiopathic hemolytic anemia (MAHA), fever, neurological abnormalities, and renal dysfunction; however, this pentad is not necessary for diagnosis. Only thrombocytopenia and MAHA without another clinically apparent etiology (e.g., disseminated intravascular coagulation, malignant hypertension, severe preeclampsia, sepsis, systemic malignancy, etc.) are required to suspect the diagnosis of TTP and to initiate therapy. MAHA is defined as nonimmune hemolysis (i.e., negative direct antiglobulin test) with prominent red cell fragmentation (schistocytes) observed on the peripheral blood smear.


Pathogenesis

The pathogenesis may be autoimmune in nature since autoantibodies against ADAMTS13 (acronym for a Disintegrin and a Metalloproteinase with Thrombospondin-1 Motifs, 13th member of the family), which cleaves von Willebrand Factor (vWF), are typically present in most cases of idiopathic TTP. These antibodies cause the absence of ADAMTS 13 protease activity and the persistence of vWF. Subsequently the procoagulation tendency dominates and causes the systemic abnormalities. 

In STEC-HUS, the toxin triggers endothelial complement deposition through the upregulation of P-selectin and possibly interferes with the activity of complement regulatory molecules. 

In aHUS, mutations in the genes coding for complement components predispose to hyperactivation of the alternative pathway of complement. 


Management

The mainstay of treatment for patients with TTP is plasma exchange (PE) in conjunction with steroids. The mortality rate of TTP prior to the use of PE was approximately 90 percent and is currently 20 percent or less in patients treated with PE. PE reverses the platelet consumption responsible for the thrombus formation and symptoms in TTP.

Rituximab is a monoclonal antibody directed against CD20 which is specific to B lymphocytes. It depletes the production of antibodies from these lymphocytes and thus has been used for antibodies-mediated diseases including TTP. Observational studies have suggested good outcomes in some settings. Rituximab should be considered in the management of TTP along with PE and well-designed prospective studies are needed to evaluate its role in TTP.

Importantly, evidence is emerging that pharmacological targeting of complement with the anti-C5 monoclonal antibody eculizumab can effectively treat not only aHUS for which it is indicated, but also STEC-HUS and TTP in some circumstances.


N. Abdel Karim, S. Haider, C. Siegrist, et al., “Approach to Management of Thrombotic Thrombocytopenic Purpura at University of Cincinnati,” Advances in Hematology, vol. 2013, Article ID 195746, 4 pages, 2013. doi:10.1155/2013/195746

Noris, M., Mescia, F., Remuzzi, G.
STEC-HUS, atypical HUS and TTP are all diseases of complement activation
(2012) Nature Reviews Nephrology, 8 (11), pp. 622-633.

Metastatic Spinal Cord Compression – a primer

  • Metastatic spinal cord compression (MSCC) may be the presenting feature of cancer in up to 20% of patients.
  • A history of persistent worsening back pain in a patient with cancer warrants urgent investigation.
  • Immediate MRI of the whole spine is the imaging modality of choice.
  • Patients with a clinical suspicion of MSCC are routinely commenced on corticosteroids, typically oral dexamethasone 8 mg twice daily, although there is limited evidence to support this practice.
  • Although there was no difference in survival, the use of steroids was associated with a significant improvement in ambulatory status at 6 months.
  • Direct decompressive surgical resection followed by radiotherapy has been shown to be superior to radiotherapy alone.
  • Failure of immediate diagnosis and treatment is associated with significant morbidity and compromised quality of life.

MSCC indications

Postgrad Med J 2008;84:418-427 doi:10.1136/pgmj.2007.067033

Hyperviscosity Syndrome

Clinical Manifestations

Hyperviscosity syndrome, seen in approximately 15% of patients with Waldenstrom macroglobulinemia, is the most serious and potentially fatal complication of macroglobulinemia.

Hyperviscosity syndrome commonly manifests as skin or mucosal bleeding, visual abnormalities, headache, vertigo, dizziness, nystagmus, deafness, ataxia and in severe cases confusion, dementia, stroke or coma. Pulmonary edema and congestive heart failure have also been reported. However, uncommonly, hyperviscosity syndrome may manifest with exertional chest pain and dyspnea without other symptoms. Tyically, symptoms improve with initiation of chemotherapy and reduction in plasma viscosity..

Elevated plasma viscosity along with characteristic symptoms can be diagnostic of hyperviscosity syndrome. Although it is usually seen with the plasma viscosity > 4 cP, the level at which patients become symptomatic is quite variable (“symptomatic threshold”). The presence of anemia or hypoxia may contribute to symptom manifestations at a marginally elevated plasma viscosity.

Diagnosis

Laboratory evaluation of a suspected hyperviscosity syndrome should include serum protein electrophoresis and immunofixation, quantitative immunoglobulin levels and plasma viscosity measurements. Additionally, a complete blood count, kidney and liver function tests, lactate dehydrogenage and disease-specific evaluation are performed.

Treatment

The immediate treatment relies on the physical removal of the IgM protein from the blood stream by plasmapheresis, while long-term management is aimed at the control of underlying disease.

Rituximab, an IgG(1)-kappa monoclonal antibody that targets the CD20 antigen on the surface of malignant and normal B lymphocytes, has been utilized in treatment as a single agent or in combination with chemotherapy.

Bendamustine hydrochloride, a novel alkylating agent, has shown efficacy in treatment of indolent non-Hodgkin lymphoma and can be administered in combination with rituximab with good outcomes.

Adapted from: World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online. Creative Commons License.