White Blood Cell Disorders

Leukemia

• Def:
  • Malignant cells (blasts) fail to mature & crowd out normal cells which leads to decreased production of normal cells
  • Neoplastic disease of the bone marrow characterized by UNREGULATED proliferation of a cell line
• Acute Leukemia:
  • rapid onset, aggressive disease cells are poorly differentiated with immature BLASTS forms
    
  • HM: BLASTS in BM which spill into the peripheral blood
• Chronic Leukemia:
  • insidious onset, usually less aggressive cells are more mature forms
• 4 Types:
  • Acute Myelocytic Leukemia ( AML)
    
  • Chronic Myelocytic Leukemia ( CML)
    
  • Acute Lymphocytic Leukemia ( ALL)
    
  • Chronic Lymphocytic Leukemia ( CLL)
• WHO classification for leukemia:
  • morphology
    
  • immunophenotyping
    
  • genetic markers
• FAB classification for leukemia:
  • classification M0-M7
    
  • Morphology & basic staining

Acute Myelocytic Leukemia ( AML)

• Etiology:
  • MC acute leukemia in adults
• Causes:
  • de novo = MC
    
  • previous underlying myelodysplastic syndrome
    
  • congenital disorders (downs/bloom)
    
  • previous chemo/radiation
    
  • environmental exposures
• Presentation:
  • associated with bone marrow dysfunction
    
  • shortness of breath
    
  • fatigue
    
  • weakness
    
  • fever (recurrent infections)
    
  • thrombocytopenia
    
  • bone pain
• Leukocytosis:
  • accumulation of blasts in the circulation leads to impaired tissue perfusion — more common in AML
  • MEDICAL EMERGENCY
  • Signs:
    • dyspnea
      
    • headache
      
    • altered mental status
  • Treatment:
    • leukapheresis and/or chemotherapy
• Peripheral Blood Smear:
  • blasts with auer rods (especially in APL)
• Complications:
  • Disseminated intravascular coagulation (DIC) with APL – M3
• Work up:
  • with neuro sxs:
    • CT/MRI
      
    • Lumbar Puncture
  • Febrile:
    • start empirical antibiotics
      
    • do blood cultures, urine cultures, and chest x-ray
  • Confirmatory Test:
    • bone marrow aspirate and bone marrowy biopsy — with blasts being >20%
    • Bone Marrow Biopsy 3 tests assist to determine prognosis:
      • Immunophenotyping by Flow cytometry
        
        • a process used to identify cells, based on the types of antigens on the surface of the cell
      • Cytogenetics
        
        • blood or bone marrow done to look for certain changes in the chromosomes
      • Molecular Studies
        • Testing for specific mutations at the DNA level through polymerase chain reaction testing( PCR)
• Prior to Treatment:
  • ECHO-> assess baseline EF prior to chemotherapy
    
    • Why: bc anthrocyclines are given during treatment – which can lead to cardiac toxicity
  • +/- Lumbar Puncture -> ONLY IF neurological findings at time of presentation
    
  • Central line Placement
    
  • PICC, Hickmann, Port
    
  • Fertility discussion and sperm banking
• Treatment:
  • Supportive:
    • IVF’s
      
    • Allopurinol
      
    • Phoslo
      
    • Tumor Lysis Syndrome management
  • TWO PHASES
    
    • 1. Induction Chemo — single regimen
      
      • Goal: rapid remission
      • Cytarabine + Anthracycline (standard ” 7+3″ )
        
      • 3-4 week hospital course
    • 2. Consolidation Chemo
      • Goal: maintain remission
      • HIDAC-> high dose cytarabine
• Tumor Lysis Syndrome:
  • Def:
    • The rapid release of intracellular ions and metabolic byproducts into systemic circulation due to lysis of tumor cells
  • Presentation
    • PUCK
    • hyperphosphatemia
    • hyperuricemia
      
    • hypocalcemia
    • hyperkalemia
      
  •  Risk for:
    • acute kidney injury(AKI)
      
    • cardiac arrhythmias
      
    • seizures
      
    • death
  • Ppx Treatment:
    • Allopurinol 300mg po daily
      
    • Phoslo 1334mg po TID
      
    • Aggressive IVF’s and strict I/O monitoring
      
    • Replace Calcium as needed-> Calcium gluconate

Chronic Myelocytic Leukemia ( CML)

• Etiology:
  • Average age: 55 y/o
  • uncontrolled clonal proliferation of mature and maturing WBCs ( granulocytes)
    
  • caused by a single, specific genetic mutation known as the Philadelphia chromosome ( T 9;22), forming the abnormal gene BCR/ABL
  •  
• Risk Factor:
  • ionizing radiation
• 3 Phases: CAB
  • chronic
    
    • mature cells proliferate along with mutated clone; normal bone marrow function intact
  • accelerated
    
    • cytogenetic abnormalities occur at a faster rate; acquired new mutations pt. become symptomatic
  • blast
    • immature cells rapidly proliferation “Blast Crisis” — mimics Acute leukemia
      
    • if the blasts reach >20% — then it is AML
• Presentation:
  • most are asymptomatic — and caught on routine blood screening
    
  • if they are farther progressed:
    
    • fever
      
    • weight loss
      
    • fatigue- most common
      
    • night sweats
      
    • splenomegaly- most common
• Work up:
  • CBC
    • Marked leukocytosis- WBC 50-100,000 with a left shift toward granulocytes = HM
  • Bone Marrow Biopsy
    • granulocytic hyperplasia
      
    • Philadelphia chromosome present
  • Cytogenetics
    • + BCR/ABL gene-> translocation (9;22) AKA Philadelphia chromosome = HM
• Treatment:
  • targeted therapy to Philadelphia chromosome t( 9;22) — would use a tyrosine kinase inhibitor (Imatinib)
    
  • allogenic stem cell transplant only proven cure

Acute Lymphocytic Leukemia ( ALL)

• Etiology:
  • children — peak onset = 2-5 years
    
  • adults have the worst prognosis
  • Lymphatic cells affected
• At-Risk:
  • –Downs Syndrome( trisomy 21)
    
  • -Blooms Syndrome
    
  • -Previous malignancy/previous chemotherapy
• 2 Main Classes:
  • 1. B-Cell Acute Lymphoblastic Leukemia = MC
    
  • 2. T-Cell Acute Lymphoblastic Leukemia — poorer prognosis
• Presentation:
  • associated with bone marrow dysfunction
    
  • Neutropenia
    
  • Anemia
    
  • Thrombocytopenia
    
  • Bone pain
    
  • *Headache- indicates CNS involvement
  • Extramedullary sites Sxs:
    • *CNS- Meningeal infiltration
      
    • Gonads-> testicular enlargement
      
    • *Spleen-> enlargement
      
    • *Lymphadenopathy
      
    • Mediastinal Mass( thymus)
• Peripheral Blood Smear:
  • (TdT) Terminal deoxynucleotidyl transferase ( +) in immature lymphoblasts
• High-Risk Pt:
  • Increasing age >35yr
    
  • T-CELL lymphoblastic leukemia
    
  • Poor( high risk) cytogenetics
    
  • No remission after 1st induction cycle
• Work up:
  • Definitive test:
    • bone marrow aspirate with bone marrow biopsy
      
    • will have blasts >20%
• Prior to Treatment:
  • ECHO
    
  • Lumbar puncture (LP)
    
    • Why: Bc High risk of CNS involvement esp. with relapse disease require prophylactic treatment of CNS
  • Placement of a central venous catheter
• Treatment:
  • Supportive:
    • 1. neutropenic diet- no fresh fruit/raw vegetables/meat well done/no raw seafood
      
    • 2. anti-emetics
      
    • 3. transfusion support (RBC/platelets)
  • 3 PHASES + CNS PROPHYLAXIS
    
    • Induction
      • need all of the following meds: VAPA
        
        • vincristine
          
        • anthracycline
        • prednisone
          
        • asparaginase
          
    • Consolidation
      
    • Maintenance
      
      • 6-mercaptopurine oral daily and methotrexate weekly along with intrathecal chemotherapy
    • CNS Prophylaxis
      • patients will receive intrathecal (IT) chemotherapy with EVERY cycle (ommya reservoir)
        
      • Includes the following chemo meds:
        
        • Methotrexate or Cytarabine
          
        • Hydrocortisone 30 mg – to prevent spinal headache and nausea/vomiting
  • Consider Stem Cell Transplantation if:
    • high risk disease patients transplant maybe recommended once patient has achieved their first remission;
    • or if patient has relapse

Chronic Lymphocytic Leukemia ( CLL)

• Etiology:
  • MC form of leukemia in western countries
  • Clonal proliferation of incompetent B-cells
    
  • Clonal B -cells get stuck in maturation sequence between pre-B cells and mature B-cells and over proliferate
• Presentation:
  • most are asymptomatic — found on CBC by accident — will show isolated lymphocytosis
    
  • painless lymphadenopathy (wax/wane)
    
  • warm autoimmune hemolytic anemia
    
  • fatigue
• Work Up:
  • Blood Smear
    • lymphocytosis
      
    • smudge cells
  • Confirmatory test
    • peripheral blood flow cytometry
• Staging System – Rai System (Stages 0-4)
  • stage 0 CLL – absolute lymphocyte count is extremely high (def over 5,000)
  • stage 1 CLL – lymphadenopathy present
  • stage 2 CLL – liver and spleen are swollen
  • stage 3 CLL – anemia present
  • stage 4 CLL – thrombocytopenia
• Treatment:
  • low risk: observation
    
    • NO B symptoms
      
    • NO progressive adenopathy/hepatosplenomegaly
      
    • NO recurrent infections
      
    • NO symptomatic anemia/thrombocytopenia
  • high risk: fludarabine
    
  • cure: stem cell transplant

Neutropenic fever

• Def:
  • MEDICAL EMERGENCY
    
  • fever greater than 38 for an hour
• Treatment:
  • panculture start broad-spectrum IV antibiotic