Heme Onc by someone who knows nothing about it

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Heme Onc by someone who knows nothing about it

• JulieAnne Gibson McGregor

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Objectives as outlined by the retired Nate
Lambert

• Recognize ACS in SCD and indications for exchange
  transfusion
• Natural history of MDS
• Management of life-threatening hemoptysis due to
  lung cancer
• Indication for splenectomy in ITP
• Diagnosis and management of CLL
• Diagnosis and management of MGUS
• Recognize CML in chronic phase

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Sickle Cell Disease

• Hemoglobinopathy characterized by a single amino
  acid substitution in the beta globin chain
• Hemoglobin S results from the substitution of a
  valine for glutamic acid as the sixth amino acid
  of the beta globin chain
• Alpha2/beta S2 poorly soluble when deoxygenated
  causing a marked decrease in red cell
  deformability and distortion into sickle shape

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Pulmonary complications of SCD

• Acute and chronic pulmonary complications
  represent the most common cause of death in
  adulthood
• Chronic- recurrent microvascular obstruction
  resulting in PHTN, endothelial dysfunction and
  parenchymal fibrosis
• Acute- infection, fat emboli, infarction from
  in-situ thrombosis, pulm edema (iatrogenic)

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Recognize Acute Chest Syndrome in Sickle Cell
Disease

• Most common form of acute pulmonary disease in
  SCD, ½ of pts.
• Most frequently reported cause of death in adults
• Risk factor for early mortality

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Recognize Acute Chest Syndrome in Sickle Cell
Disease

• New pulmonary infiltrate involving one complete
  lung segment (not atelectasis)
• Chest Pain
• T 38.5
• Tachypnea, Wheezing or Cough

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Etiology of ACS (Precise etiology unclear)

• Pulmonary infarction (microvascular)
• Fat embolism
• Chlamydia pneumonia infection
• Mycoplasma pneumoniae infection
• Viral infection
• Mixed infections
• Other pathogens

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Clinical findings of ACS

• Fever
• Chest and or Extremity Pain
• Dyspnea
• Nonproductive cough
• Tenderness over the ribs or sternum
• Leukocytosis
• Pulmonary consolidation
• Thrombocytopenia or Thrombocytosis
• Falling hemoglobin concentration
• Elevated LD and Bili

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Diagnosis of ACS

• No currently laboratory or radiographic finding
  permits the differentiation of ACS from other
  acute pulmonary manifestations of SCD, including
  pneumonia and infarction from large vein thrombis
  (PE).

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Management of ACS

• Supportive care
• Community acquired pneumonia coverage
• Supplemental oxygen to maintain PaO2 of 70
• Judicious use of opioid analgesics
• Incentive spirometry

• Some data for bonchodilators
• Hydration attempting to avoid pulmonary edema
• RBC transfusion matched for C, E and Kell
  antigens
• Exchange transfusion

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Indications for Exchange Transfusion

• Progressive infiltrates and hypoxemia refractory
  to conventional therapy
• Reduction of the HbS level to below 30 and a Hct
  of 30 can lead to marked improvement in the
  majority of cases of ACS

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Natural History of Myelodysplastic Syndromes

• MDS- series of hematologic conditions
  characterized by chronic cytopenias (anemia,
  neutropenia, thrombocytopenia) accompanied by
  abnormal cellular maturation
• MDS leaves pts at risk for symptomatic anemia,
  infection, bleeding and progression to acute
  leukemia

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Natural History of Myelodysplastic Syndromes

• Average age 65 to 70
• Patients who evolve to AML from MDS are less
  reponsive to standard treatment than is de novo
  AML.
• Mainstays of therapy- RBC and platelet
  transfusions as needed and amtibiotic supportive
  care when required

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Classification of MDS

• Refractory anemia (RA)- less than 5 BM blasts
• Refractory anemia with ringed sideroblasts
  (RARS)- 15 ringed
  sideroblasts
• Refractory anemia with excess blasts (RAEB)- 5-19
  BM blasts
• Chronic myelomonocytic leukemia (CMML)- up to 20
  BM blasts peripheral blood monocyte count 1000
• RAEB in transformation- 12-30 BM blasts

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Natural History of Myelodysplastic Syndromes

• Most patients with MDS die of consequences of
  bone marrow failure rather than transformation to
  AML
• Low risk (blasts 100) median survival
  4.9 years
• High risk (blasts 5, MCV 0.5 years
• Intermediate risk (all others) median survival
  1.8 to 2.0 years

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Management of life-threatening hemoptysis due to
lung cancer

• Without looking this up I suppose the answer is
• Similar to management of life threatening
  hemoptysis in other situations
• Find out code status
• Attempt to intubate the lung that isnt bleeding
• Activated factor VII
• Transfusion and saline to maintain blood volume
• Prayer

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Management of life-threatening hemoptysis due to
lung cancer

• Definition of massive hemoptysis is expectoration
  of blood exceeding 100 to 600 mL in 24 hours.
• 80 mortality for people with massive hemoptysis
  for any reason
• Bronchogenic carcinoma is an infrequent cause of
  massive bleeding although it commonly causes
  nonmassive hemoptysis.
• Patients with massive hemoptysis typically had
  large, centrally located tumors, especially
  squamous cell carcinoma

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Management of life-threatening hemoptysis due to
lung cancer

• No consensus regarding the optimal management of
  people with massive hemoptysis
• Insure adequate airway protection, ventillation
  and cardiovascular function.
• Reverse coagulation disorders (I didnt think of
  that one, duh)
• Consult pulmonary (?bronch) and thoracic surgery
  (?pulmonectomy) and invasive radiology (?arterial
  embolization).
• Place the bleeding lung in dependent position to
  reduce spillage into healthy lung

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Indication for Splenectomy in ITP

• Idiopathic thrombocytopenic purpura also known as
  immune thrombocytopenic purpura and ITP
• Thrombocytopenia, with an otherwise normal CBC
  and WBC diff, including a normal peripheral blood
  smear
• No clinically apparent associated conditions or
  medications that may cause thrombocytopenia

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Indication for Splenectomy in ITP

• Pathogenesis of ITP is presumed to be related to
  the presence of platelet specific autoantibodies
• Goal of treatment is to provide a safe platelet
  count to prevent major bleeding rather than
  correcting the underlying disease.
• Major bleeding is rare in pts with 10,000

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Indication for Splenectomy in ITP

• Spontaneous remissions are unusual in adults- one
  quote 9
• Often adults treated with steroids however
  patients with mild and asymptomatic
  thrombocytopenia with plts 30,000- 50,000 often
  have a stable and benign course
• No good data on adults with ITP and spont
  remission, major or death from bleeding

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Indication for Splenectomy in ITP

• General Treatment Goals - treat moderate to
  severe thrombocytopenia who are bleeding or at
  risk
• - limit duration of treatment unless symptoms
  persist
• - mild, asymptomatic thrombocytopenia should
  not be treated.

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Indication for Splenectomy in ITP

• Treatment is steroids, IVIGor anti-Rh(D) in pts
  whose red cells are Rh(D) .
• Splenectomy is traditional second-line treatment
  in adults with ITP who fail to achieve a safe
  platelet count with initial prednisone therapy.
• Splenectomy no appropriate in mild or mod
  thrombocytopenia and minor bleeding

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Indication for Splenectomy in ITP

• Splenectomy should be deferred for 4-6 weeks
  after diagnosis
• Estimate for complete remission following
  splenectomy in 65
• Younger patients in general respond better to
  splenectomy
• Risk for splenectomy increases with age, obesity
  and comorbid conditions

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If you decide against splenectomy or it failed

• Continuous low dose steroids
• Ritux
• Cyclophosphamid and azathioprine
• Vincristine or vinblastine
• Danazol
• Aminocaproid acid
• Thrombopoiesis stimulating agent
• Other

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Diagnosis and Management of CLL

• CLL- one of the chronic lymphoproliferative
  disorders (lymphoid neoplasms) progressive
  accumulation of functionally incompetent
  lymphocytes which are monoclonal in origin
• Median age 61
• Age range 25 to 84
• Slight male predominance

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Diagnosis and Management of CLL

• Initial presenting findings- lymphadenopathy,
  splenomegaly, hepatomegaly, WBC 100,000, Hgb
  
• Symptoms range from totally asymptomatic to
  weight loss, fevers, night sweats, extreme
  fatigue
• ALC threshold 5000 for diagnosis

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Diagnosis and Management of CLL

• Peripheral blood smear- mature appearing small
  lymphocytes account for 50 or WBC
• May also see lymphocytes which appear flattened
  or smudged in the process of being spread on the
  glass slide when looking at smear
• Smudge cells reflect fragility of cells

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Smudge Cells
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Diagnosis and Management of CLL

• CLL lymphocytes are described as mature appearing
  cells but they are immature both functionally and
  developmentally
• B-CLL- low levels of surface membrane
  immunoglobulin, expression of B cell antigens
  (CD19, CD21, CD 23 ect), and expression of CD5 a
  T cell associated antigen.

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Diagnosis and Management of CLL

• 1 point for each of below, 4-5 points 97
  accurate
• Weakly positive surface immunoglobulin stain
• CD5
• CD23
• CD79b or CD22 weakly
• FMC7 negative

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Diagnosis and Management of CLL- minimum dx
criteria

• ALC in the peripheral blood 10,000 with a
  preponderant population of morphologically mature
  appearing small lymphocytes
• Normo to hypercellular bone marrow with
  lymphocytes accounting for 30 of all nucleated
  cells
• low levels of surface membrane immunoglobulin,
  expression of 1 or more B cell antigens, and
  expression of CD5

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Diagnosis and Management of CLL

• A series of 25 cases of T cell CLL has been
  reported but many of these cases have been
  reclassified and suggestion was made to discard
  this diagnosis entirely.
• Major complications of CLL arise from cytopenias
  and immune dysfunction, anemia, and
  thrombocytopenia
• Infections lead to 50 of deaths from CLL

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Diagnosis and Management of CLL

• Depressed immune function from hypogammaglobulinem
  ia can be improved with IVIG for patients with
  pattern of repeated infections, especially
  pneumonia and sepsis.
• Sinobronchial and other bacterial infections can
  be treated with antibiotics alone
• Acyclovir for herpes simplex and zoster

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Diagnosis and Management of CLL

• Impaired T cell function can lead to
  opportunistic infections
• In rare cases may need to use GCSF
• RBC tx and epo for anemia
• Thrombocytopenia- steroids, danazol and IVIG
• Survival is similar to aged matched controls

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Diagnosis and Management of MGUS

• Presence of a serum monoclonal protein
  (M-protein, whether IgA, IgG or IgM) at a
  concentration
• Fewer than 10 plasma cells in the bone marrow
• Absence of lytic bone lesions, anemia,
  hypercalcemia and renal insufficiency related to
  the plasma cell proliferate process

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Diagnosis and Management of MGUS

• Predilection for the development of multiple
  myeloma or a related malignancy at the rate of 1
  per year
• No evidence for a neoplastic plasma cell
  proliferative disorder or a B cell
  lymphoproliferative disorder
• Asymptomatic
• M protein detected with SPEP followed by
  immunoelectrophoresis or immunofixation for the
  identification of the M protein type.

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Diagnosis and Management of MGUS

• Major reason for concern in the pt with MGUS is
  the risk of progression to a symptomatic plasma
  cell proliferative disorder
• Pt with IgG or IgA MGUS may progress to multiple
  myeloma, primary amyloidosis or a related plasma
  cell disorder
• Pt with IgM MGUS may progress to a
  lymphoproliferative disorder (lymphoma, CLL,
  Waldenstroms)

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Diagnosis and Management of MGUS

• MGUS found in 1 to 2 of adults
• Higher in patients over age 70
• 2-3 fold higher prevalence in black patients
• Higher rates in men than women

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Diagnosis and Management of MGUS

• In order to differentiate MGUS from a related
  plasma cell malignancy, pts should have a CBC,
  creat, Ca, and complete radiographic bone survey
  of the skeleton.
• Abnormalities of the above should have additional
  tests to determine the etiology of the
  abnormalities and whether thany are indeed
  related to a plasma cell prolif. d/o.

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Diagnosis and Management of MGUS

• Bone marrow aspiration and biopsy is indicated in
  all patients with an M proteint 1.5 gm/dL, non
  IgG MGUS, abnormal serum free light chain ratio
  and all pts with abnormal CBC, creat, Ca or bone
  survey.
• BM bx can be deferred in elderly asymptomatic pts
  with a small IgG monoclonal protein who have f/u

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Diagnosis and Management of MGUS

• Light chains in the urine may be found in small
  amount in MGUS
• 10 or more of plasma cells in the BM is
  diagnostic of MM but pts may have smoldering MM
  and remain stable during long term
• Repeat SPEP 6 months after first abnormal one and
  if stable annually thereafter.

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Recognize CML in Chronic Phase

• CML is shor for chronic myelogenous leukemia or
  chronic myelocytic leukemia or chronic myeloid
  leukemia
• One of the myeloproliferative disorders along
  with PV, ET and agnogenic myeloid metaplasia now
  call chronic idiopathic myelofibrosis
• Characterized by the proliferation of a single
  myeloid cell type- excess neutrophills in CML

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Recognize CML in Chronic Phase

• Myeloproliferative disorders
• - clonal disorders of hematopoiesis that arise
  in a hematopoietic stem cell or early progenitor
  cell
• - characterized by dysregulated production of
  a particular lineage of mature myeloid cells with
  fairly normal differentiation
• - variable tendency to progress to acute leuk

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Recognize CML in Chronic Phase

• CML is associated with an abnormal chromosome 22
  known as the Philadelphia chromosome Bcr-Abl
• 15-20 of cases of leukemia in adults
• Median age at presentation is 50
• Annual incidence of 1 to 2 cases per 100,000
• Slight male predominence

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Recognize CML in Chronic Phase

• Uncontrolled production of maturing granulocytes,
  predominantly neutrophils but also eosinophils
  and basophils.
• 3 phases of CML- chronic phase, accelerated
  phase, and blast crisis.
• 85 of pts present in the chronic phase

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Recognize CML in Chronic Phase

• Chronic phase- large increase in the pool of
  committed myeloid progenitors leading to
  peripheral blood leukocytosis and often
  thrombocytosis
• Left shift
• Basophillia
• Splenomegaly, occasional hepatomegaly or
  adenopathy (myelofibrosis and extramedullary
  hematopoiesis)

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Recognize CML in Chronic Phase

• Often asymptomatic
• Symptoms include fatigue, malaise, weight loss,
  excessive sweating, abdominal fullness, early
  satiety, sternal tenderness, gout, and bleeding
  episodes due to platelet dysfunction.

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Other phases of CML, just for fun

• Accelerated phase- neutrophil differentiation
  becomes progressively impaired and leukocyte
  counts are more difficult to control with
  myelosuppressive meds
• Blast crisis- condition resembling acute leukemia
  in which myeloid or lymphoid blasts fail to
  differentiate