TUMOR LYSIS SYNDROME

Tumor lysis syndrome (TLS)-metabolic abnormalities that result from the death of  tumor cells and release of their contents into the circulation

The classic triad of TLS includes:

  • HYPERURICEMIA
  • HYPERPHOSPHATEMIA 
  • HYPERKALEMIA

ETIOLOGY

  • Burkitt's lymphoma
  • Lymphoblastic lymphoma
  • ALL,T-lineage ALL with hyperleukocytosis and 
  • Extensive extramedullary disease
  • Hodgkin disease
  • Large-cell lymphoma
  • Neuroblastoma
  • Medulloblastoma
  • Breast carcinoma
  • Small-cell lung carcinoma

 

 

PATHOGENESIS

SYMPTOMS (AS NOTED BY PARENTS)

  • Abdominal pain or fullness
  • Back pain
  • Vomiting
  • Diarrhea
  • Signs and symptoms of dehydration
  • Anorexia/vomiting/cramps
  • Spasms/Tetany/Seizure
  • Alterations in consciousness

SIGNS (AS NOTED BY THE PHYSICIAN)

  • Blood pressure
  • Heart rate and rhythm
  • Abdominal masses
  • Pleural effusions or ascites
  • Signs of SVCS or SMS
  • Signs of cerebral anoxia

INVESTIGATIONS

  • CBC
  • Serum sodium/ potassium
  • Chloride/bicarbonate
  • Calcium/phosphorus/uric acid/BUN/Cr levels
  • Urinalysis
  • Serum albumin
  • EKG
  • USG/CT

TYPES OF TLS

Lab TLS Clinical LS
Uric Acid>476µmol/L

Renal insufficiency

Creatinine>1.5ULN

Potassium>6mmol/L Cardiac arrhythmia not due to drug
Phosphorous>2.1mmol/L Seizures not due to drug
Calcium <1.75mmol/L  

TREATMENT

Hydration  ¼ DNS 40mEq/L NaBicarb 2-4 times maintaince rate
Alkanization Maintain pH 7-7.5
Diuresis

Lasix 1mg/kg

Mannitol 0.5mg

Uric Acid Reduction

Allopurinol 10mg/kg/d

Urate Oxidase 0.2mg/kg/d

SIDE EFFECTS

  • Skin rash
  • Steven Johnson Syndrome
  • To watch when given with 6MP as
  • Metabolized by Xanthine Oxidase
  • Dose to be reduced in renal failure
    Metabolic Abnormalities Monitor electrolytes Ca, Mg, Po4, Uric Acid
    Hyperkalemia

    Kayexalate 1g/kg with 50% sorbitol

    Calcium Gluconate 100-200mg/kg

    Insulin 0.1u/kg with 2ml/kg 25% Dx

    Hyperphosphatemia Aluminium hydroxide 15ml q6-8 h
    Hypocalcemia Calcium Gluconate if symptomatic
    Supportive treatment

    Plt tranfusion

    FFP/Vit K

    Avoid Packed red cell transfuion

    Dialysis

    Volume overload

    Hyperkalemia

    Hyperphosphatemia

    Hyperuricemia

    Symptomatic hypocalcemia

ADDITIONAL THERAPIES

Intravenous low-dose prednisone continuous infusion treatment can prevent the progression to tumor lysis syndrome and it may be used for the patients presenting with white blood cell counts between 100 and 400 x 10(9)/l in centers where leukoapheresis is not readily available  Acta Haematol. 2009;121(1):56-62.

 IV allopurinol is as efficacious and safe as oral allopurinol and will be of significant benefit to patients at risk of TLS unable to take oral medication

J Clin Oncol 18:1758-1763. 2000

 SUPERIOR VENA CAVA SYNDROME AND SUPERIOR MEDIASTINAL SYNDROME

The signs and symptoms resulting from compression, obstruction, or thrombosis of the superior vena cava. The term SMS is used when tracheal compression also occurs.In children with mediastinal masses,

tracheal compression and respiratory embarrassment usually coexist with SVCS.

The location of the blocked area and how fast the blockage occurs affect the symptoms and severity. If the blockage is above where the superior and inferior vena cava veins join, other veins can become larger over

time and take over the increased blood flow. The symptoms may be milder. If the blockage occurs below where the superior vena cava and inferior vena cava meet,the blood must be returned to the heart by the veins in the upper abdomen and the inferior vena cava, which require higher pressure. Symptoms may be more severe.

CORD COMPRESSION

A mass compromising the integrity of the spinal cord, conus medullaris, or cauda equina requires urgent attention to minimize long-term neurologic dysfunction. Epidural compression may occur with a known malignancy

or may be the presenting symptom of an undiagnosed malignancy.Acute compression of the spinal cord occurs in 3% to 5% of children with cancer, often at diagnosis. Local or radicular back pain occurs in 80% of children with cord compression.

CAUSES

  • Sarcomas
  • Neuroblastoma
  • Germ cell tumors
  • Lymphoma
  • Dropped metastases from primary CNS
  • Tumors
  • Wilms' tumor

SYMPTOMS

  • Children with cancer and back pain should be considered to have spinal cord compression until proven otherwise
  • Pain can start weeks to months before diagnosis
  • Long-standing cord compression can present as progressive weakness, sensory abnormalities and paresis.
  • Once neurologic abnormalities are apparent, paraplegia and quadriplegia can occur rapidly and may be irreversible
  • Compression at the level of the cauda equine may present with urinary and fecal incontinence.

PATHOGENESIS

EXAMINATION (BY THE PHYSICIAN)

  • Detailed neurological examination
  • Power
  • Tone
  • Reflexes
  • Determination of a sensory level is essential
  • A rectal examination assesses sphincter tone
  • Localized tenderness to vertebral percussion

Any child who is not ambulatory at the time of clinical presentation, independent of the duration of dysfunction before evaluation, should undergo imaging immediately.

INVESTIGATIONS

  • Spine radiographs
  • Bone scans
  • Lumbar myelography
  • T1- and T2-weighted MRI scans, performed
  • With and without gadolinium
  • CSF examination
    Sign Spinal Cord Conus Meduaris Cauda Equina
    Weakness Symm/Profound Symm/Variable Asymm
    Tendon reflexes      
    Babinsky Extensor Extensor Planter
    Sensory Symm/Sens level Symm Asymm
    Spincter Abnormality Late Early Maybe Spared
    Progression Rapid Variable Variable

    INVESTIGATIONS

  • Rapidly progressive spinal cord dysfunction or an anatomic level of dysfunction- dexamethasone bolus 1.0 to 2.0 mg/kg
  • MRI: For the child with cancer and back pain in whom cord compression is possible but there is no loss of function or rapid neurologic progression of symptoms-dexamethasone 0.25 to 0.5 mg/kg or PO q6 hourly. 
  • Local radiation therapy
  • Surgery- laminectomy and posterior decompression
    •  Tumor identification
    • Progressions of symptoms
    • Despite RT
  • Chemotherapy -spinal cord compression due to lymphoma, leukemia and neuroblastoma
  • Multidisciplinary approach
  • If the tumor is radioresponsive, radiation therapy is often the treatment of choice. Supervoltage techniques are used, and daily doses between 180 and 400 cGy are given with dexamethasone.