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Myeloid Leukemia Complications - Introduction to General Medicine - Lecture Slides, Slides of Medicine

Myeloid Leukemia Complications, Induction Chemotx, Transfusion of Platelets, Leukapheresis, Mature Myeloid Cells, Production of Various Cytokines, Leukostasis in Aml, Dehydrogenase Serum Levels are some points in Introduction to General Medicine lecture. This lecture is one of 61 lectures you can find here for this course.

Typology: Slides

2011/2012

Uploaded on 12/13/2012

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Case #1
52 yo M no significant PMHx presents with general
malaise for several days, headache and shortness of
breath. Exam reveals palor and scattered petechiae.
Found to have 95,000 WBC with HCT of 22 and
platelet count of 22,000. Chem panel unremarkable.
Treatment of this condition would involve:
A) Induction chemotx with anthracycline/cytarabine
B) Leukapheresis
C) Transfusion of platelets, PRBCs followed by leukapheresis
D) Running throughout the hospital yelling as loudly as possible
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Case

  • 52 yo M no significant PMHx presents with general malaise for several days, headache and shortness of breath. Exam reveals palor and scattered petechiae. Found to have 95,000 WBC with HCT of 22 and platelet count of 22,000. Chem panel unremarkable. Treatment of this condition would involve: A) Induction chemotx with anthracycline/cytarabine B) Leukapheresis C) Transfusion of platelets, PRBCs followed by leukapheresis D) Running throughout the hospital yelling as loudly as possible

Leukostasis

  • Leukostasis – predominantly in those with WBC

counts > 100,000 (10% of patients); can also be

seen in patients with WBC > 50,

  • Most common in those with M4 or M5 leukemia
  • Function of the blast cells being less deformable than mature myeloid cells. As a result, intravascular plugs develop.
  • High metabolic activity of blast cells and local production of various cytokines contribute to underlying hypoxia

Leukostasis

• Common symptoms

  • Pulmonary: dyspnea, chest pain
  • CNS: headaches, altered mentation, CN

palsies, ocular symptoms

  • Priapism
  • Myocardial Infarction

Leukostasis

  • Treatment
    • Chemotherapy with induction agents (e.g cytarabine, anthracycline) or with high dose hydroxyurea
    • Consider low dose cranial irradiation to prevent cell proliferation in the CNS (can see intracranial hemorrhage in patients with leukostasis)
    • Avoid PRBC transfusion if possible as additional blood elements contribute to the hyperviscosity
    • In patients that are unable to undergo immediate chemotx (e.g renal insufficiency, metabolic derangements, etc), leukapheresis is a 2 nd^ option

Leukapheresis

  • Bug G et al (2007) - Retrospective study from Germany of 53 newly diagnosed cases of AML and hyperleukocytosis. Cohort A – Chemotx without leukoreduction (28 patients). Cohort B – Chemotx followed by leukapheresis (25 patients). - By day 21 -> 13 of 53 patients had died with a lower risk of early death in Cohort B compared to Cohort A (16% vs. 32% respectively; p = 0.015). - Dyspnea (p = 0.005), elevated creatinine (p = 0.028), and higher lactate dehydrogenase serum levels (p = 0.021) were independent risk factors for early death. - At a median follow-up of 24.2 months, the overall survival was similar in both cohorts (Cohort A, 7.5; Cohort B, 6.5 months). (eg, Leukapheresis had no impact on long term survival)

Leukapheresis

• Giles et al (2001) - 146 patients with

newly-diagnosed AML (APL excluded) and

an initial WBC count > 50 x 10(9)/L of

whom 71 underwent leukapheresis.

  • Pheresis reduced 2-week mortality rate (p =
  • No evidence that pheresis lengthened longer-

term or overall survival; actually data to

suggest the opposite (p = .06)

Tumor Lysis Syndrome

• Characterized by metabolic derangements

caused by massive release of cellular

components following lysis of malignant

cells

• Commonly seen in malignancies with high

rates of cell proliferation (esp. ALL,

Burkitt’s lymphoma); also can be seen with

AML

Tumor Lysis Syndrome

  • Tumor lysis syndrome - hyperphosphatemia,

hyperkalemia, hyperuricemia, hypocalcemia and

uremia

  • Retrospective study of 788 patients (433 adults) found incidence of hyperuricemia and TLS to be 14.7%/3.4% in patients with AML compared to 21.4%/5.2% in patients with ALL and 19.6%/6.1% in patients with NHL
  • Electrolyte abnormalities can occur without the

entire spectrum of TLS or even before tx is

initiated

  • Hyperuricemia
  • Lactic acidosis

Tumor Lysis Syndrome

  • Prevention and management
    • IV hydration : promotes excretion of uric acid and phosphate; improves renal blood flow/GFR
    • Allopurinol → competitive inhibitor for xanthine oxidase. Therefore, ↓ conversion of purine metabolites to uric acid - However, must consider buildup of xanthine crystals → acute obstructive uropathy (HYDRATE!!!)
    • Recominant urate oxidase (rasburicase)
      • Promotes conversion of uric acid to allantoin (highly soluble; urinary excretion)
      • Indicated in patients at high risk of TLS (Burkitt’s Lymphoma, B-ALL, ALL (WBC >100,000), AML (WBC >50,000)
      • Also indicated in patients that develop hyperuricemia despite allopurinol
    • Dialysis can be used in severe cases
    • Urine alkalization is NOT recommended – does not increase solubility of xanthine/hypoxanthine with an increased propensity to develop xanthine-obstructive uropathies (esp with allopurinol use)

Greer JP, Kinney MC. Acute nonlymphocytic leukemia. In: Lee GR, Bithell TC, Foerster J, et al, eds. Clinical Hematology. 9th ed. Philadelphia, Pa: Lea & Febiger;1993:1920-1945. Wintrobe◌ํs

AML M3 (Promyelocytic)

Brunning, RD, McKenna, RW. Tumors of the bone marrow. Atlas of tumor pathology (electronic fascicle), Third series, fascicle 9, 1994,Washington, DC. Armed Forces Institute of Pathology.

Coagulation cascade

DIC

  • Common symptoms/findings
    • in addition to weakness (anemia), infections/fever (malfunctioning WBCs)
    • petechiae, ecchymoses, hematuria, bleeding from venipuncture sites
    • migratory thrombophlebitis (Trousseau’s syndrome)
    • nonbacterial thrombotic (marantic) endocarditis
    • DVT/PE
  • Lab findings
    • Prolonged PT/INR, PTT
    • microangiopathic anemia (schistocytes)
    • thrombocytopenia
    • elevated fibrin split products
    • elevated D-dimer
    • low fibrinogen