Govardhanan Nagaiah, Quoc Truong, and Manish Monga
SPINAL CORD COMPRESSION
■Spinal cord compression (SCC) is an oncologic emergency, as delay in recognition and therapy can cause irreversible loss of neurologic function.
■SCC is diagnosed in more than 30% of all patients with disseminated cancer, and roughly 5% to 10% of all patients experience cord dysfunction.
■SCC most often involves the thoracic spine (60%), followed by the lumbosacral spine (30%) and cervical spine (10%).
Etiology
■The three most common underlying cancer diagnoses associated with SCC are lung cancer (24.9%), prostate cancer (16.2%), and multiple myeloma (11.1%). The highest cancer-specific incidence rates are seen in patients with multiple myeloma (15%), Hodgkin and non-Hodgkin lymphomas (13.9%), and prostate cancer (5.5%).
■Hematogenous seeding of tumor to vertebral bodies is the most common cause of spinal metastases, followed by direct extension and cerebrospinal fluid spread.
■SCC, infrequently, is the first sign of malignancy.
Clinical Manifestations
■Pain is usually the first symptom of SCC, often worse with recumbency. Over time, pain may develop a radicular quality.
■Muscle weakness.
■Sensory loss.
■Bladder and bowel dysfunction.
■Ataxia.
■Thorough physical examination should be performed including percussion of the spinal column, evaluation for motor and sensory deficits including pinprick testing, straight-leg raising, and rectal examination.
Diagnostic Imaging
■Magnetic resonance imaging (MRI) of the entire thecal sac is the preferred modality for initial evaluation of a patient with suspected SCC. Advantages of MRI include ability to define adjacent soft tissues and bone, avoids the need for lumbar or cervical puncture as required with myelography, and can safely be performed in patients with brain metastases, thrombocytopenia, or coagulopathy. MRI without contrast may be preferred in patients with renal failure with a creatinine clearance of less than 60 mL per minute.
■Computerized tomography (CT) myelography is less often used since the widespread utilization of MRI. CT myelogram and MRI have roughly equivalent sensitivity and specificity. CT myelography may be preferred in patients with mechanical valves, pacemakers, paramagnetic implants, and shrapnel; patients with significant pain since MRI requires the patient to lie still; patients requiring CSF analysis to rule out leptomeningeal metastases.
■Other imaging modalities include CT, conventional spinal radiographs, and bone scan; however, none are reliable enough to replace either MRI or myelography.
Differential Diagnosis
■Musculoskeletal disease
■Spinal epidural abscess
■Metastatic disease with vertebral metastases without cord compression and leptomeningeal metastases
■Radiation myelopathy from prior radiation to the spine
Treatment of Spinal Cord Compression
■The goals of treatment for SCC include pain control, preservation, or improvement of neurologic function and avoidance of complications from tumor growth.
■The most important prognostic factor for regaining ambulation after treatment of SCC is pretreatment neurologic status.
■Begin treatment with a “loading” dose of dexamethasone, 10 mg intravenously (IV), followed by 4 mg IV infusion 6 hours later and every 6 hours thereafter. In a trial comparing dexamethasone bolus of 10 mg or 100 mg IV, both followed by 16 mg daily orally had no differences in pain control or neurologic outcome. Cochrane meta-analysis concluded that higher initial steroid doses were not associated with better outcomes, but increased the incidence of serious adverse events related to glucocorticoid side effects.
■Surgical and radiation oncology consultation(s) are immediately required after diagnosis, and further therapy is decided on the basis of clinical signs and symptoms, availability of histologic diagnosis, spinal stability, and previous therapies.
■In a study with symptomatic patients with SCC caused by metastatic tumors other than lymphoma, initial debulking surgery followed by radiation resulted in 4 times longer duration of maintained ambulation after treatment, and 3 times higher chance of regaining ambulation for nonambulatory patients, than that with radiation alone. In addition, patients who receive combined-modality therapy achieve superior pain control and bladder continence. Patients treated with radiation therapy alone require more steroids and narcotics and are less likely to maintain continence.
■Patients with spinal instability even in the absence of clinical signs and symptoms should undergo surgery unless otherwise contraindicated.
■Radiotherapy (RT) may be used to treat radiosensitive tumors (breast, prostate, lymphoma, multiple myeloma, and neuroblastoma) in asymptomatic individuals and in those who are symptomatic but are poor surgical candidates. Standard radiation dosages range from 2,500 to 4,000 cGy delivered in 10 to 20 fractions. In patients with relatively short life expectancy, a short course of external beam RT (one fraction of 8 Gy) produces similar palliation. Stereotactic body radiotherapy (SBRT) with a single 24 Gy fraction has also been found to give excellent tumor control, even in patients with relatively radioresistant tumors such as melanoma and renal cell cancer.
■Chemotherapy may be considered first-line therapy for patients with chemosensitive malignancies (i.e., Hodgkin lymphoma, non-Hodgkin lymphoma, neuroblastoma, germ cell neoplasms, and breast and prostate cancer) and in individuals who are not candidates for radiation or surgery. Chemotherapy may be an attractive option since it can also treat tumor deposits elsewhere in the body.
SUPERIOR VENA CAVA SYNDROME
■Superior vena cava (SVC) syndrome can occur in any condition that obstructs blood flow through the SVC. This commonly occurs as a manifestation of either primary or metastatic malignancy (extrinsic), thrombosis associated with malignancy or central venous access devices (intrinsic), or combination of both.
■SVC syndrome can result in interstitial edema of the head and neck, which may narrow the laryngeal lumen causing airway compromise, and cause cerebral edema leading to cerebral ischemia, herniation, and death.
Etiology
■SVC syndrome is caused by an intrathoracic malignancy in 60% to 85% of cases and SVC obstruction if often a presenting symptom of a previously undiagnosed tumor.
■Small cell lung cancer (SCLC) and non–small cell lung cancer (NSCLC). SVC syndrome occurs in 10% of SCLC cases at presentation; however, NSCLC is a more frequent cause because of higher incidence.
■Non-Hodgkin lymphoma, especially diffuse large cell lymphoma, primary mediastinal large B-cell lymphoma, or lymphoblastic lymphoma in the anterior mediastinum. Hodgkin lymphoma is rarely a cause of SVC syndrome.
■Other malignant tumors include thymoma, primary mediastinal germ cell neoplasms, mesothelioma, and solid tumors with mediastinal lymph node metastases (e.g., breast cancer).
■Nonmalignant disorders include thrombosis (commonly related to indwelling intravascular devices), fibrosing mediastinitis (commonly associated with fungal infections), and postradiation fibrosis.
Clinical Manifestations
■Clinical symptoms may occur acutely or gradually.
■Dyspnea is the most common symptom.
■Other symptoms include facial swelling or head fullness, arm swelling, cough, chest pain, or dysphagia.
■Physical examination findings frequently include facial edema and venous distension of the neck and chest wall. Facial plethora, arm edema, and cyanosis are less frequent.
Diagnostic Imaging
■Contrast-enhanced CT is the most useful imaging study as it can define the extent of venous blockage and identify the underlying cause of venous obstruction.
■Chest radiograph is often abnormal and common findings include mediastinal widening and pleural effusion.
■Venography is considered the gold standard for identifying SVC obstruction; however, it does not identify the cause of obstruction unless thrombosis is the sole etiology.
■Magnetic resonance venography is another modality useful for patients with contrast dye allergy.
■Radiocontrast or other injections into veins of the affected extremity are not recommended because of the risk of extravasation.
Treatment
■Treatment of SVC syndrome depends upon the underlying etiology, extent of disease, pace of symptoms progression, and overall prognosis which is linked to the type of malignancy.
■Current guidelines suggest obtaining accurate histologic diagnosis prior to starting therapy, and consider upfront use of endovascular stents in symptomatic patients to provide more rapid relief than can be achieved with RT. RT may obscure the histologic diagnosis. Most malignancies causing SVC syndrome can be identified with minimally invasive techniques including sputum cytology, pleural fluid cytology, bone marrow biopsies, and biopsy of lymph nodes. Bronchoscopy, mediastinoscopy, video-assisted thoracoscopy, and thoracotomy may be required in certain cases.
■Exceptions to above guidelines are patients with respiratory compromise (e.g., stridor due to central airway obstruction or severe laryngeal edema) or those with coma from cerebral edema. These patients require immediate stent placement and RT.
■Supportive care measures include elevation of the head of the bed, supplemental oxygen, and bed rest.
■Glucocorticoids are effective in reversing symptoms due to SVC syndrome caused by steroid-responsive malignancies such as lymphoma or thymoma. For patients undergoing RT for laryngeal edema, steroids are commonly given to reduce swelling.
■Use of loop diurects may provide transient, symptomatic relief of edema.
■Chemotherapy is the treatment of choice for patients with SCLC, NHL, or germ cell cancer (and possibly breast cancer) presenting with symptomatic SVC syndrome.
■Therapy of choice for NSCLC presenting with SVC syndrome includes endovascular stent placement and radiation therapy.
■Anticoagulant or thrombolytic therapy may be indicated for caval thrombosis and catheter-associated thrombosis.
■Surgery is rarely performed in malignant causes of SVC syndrome and most often reserved for nonmalignant causes. One possible exception is malignant thymoma and thymic carcinoma.
HYPERCALCEMIA
Etiology
Hypercalcemia occurs in about 20% to 30% of all cancers and over 30% of all patients with hypercalcemia have an underlying malignancy (Table 36.1).
Clinical Signs and Symptoms
■Symptoms of hypercalcemia depend on the rapidity of onset of hypercalcemia. Patients with chronic hypercalcemia may tolerate levels well in excess of 14 mg/dL without any apparent symptoms.
■Signs and symptoms include
•Dehydration, weakness, fatigue, and pruritus.
•CNS changes (i.e., hyporeflexia, mental status changes, seizure, coma, and proximal myopathy) and GI or genitourinary tract (GI: weight loss, nausea/vomiting, constipation, ileus, polyuria, polydipsia, azotemia, dyspepsia, and pancreatitis).
•Cardiac symptoms: Bradycardia, short-QT interval, wide T wave, prolonged PR interval, arrhythmias, and cardiac arrest.
Diagnosis
■A diagnosis of hypercalcemia is primarily made from serum levels of calcium (Table 36.2). Testing of ionized calcium may be indicated in some settings.
■The calcium concentration [Ca] usually changes by 0.8 mg/dL for every 1.0 g/dL change in plasma albumin concentration.
■Formula for corrected serum calcium concentration:
•(mg/dL) = serum Ca (measured) + 0.8 × [4- serum albumin concentration (g/dL)]
■In hypercalcemia of malignancy, serum intact parathormone (iPTH) level is low or undetectable.
General Principles of Treatment
■Unfortunately, hypercalcemia most often occurs in advanced stages of disease and in patients who have progressed through available standard chemotherapy. In patients with solid tumor primary cancers, survival is often <6 months after hypercalcemia is diagnosed.
■Any symptomatic patient with hypercalcemia, regardless of absolute serum calcium level, should be treated for correction of the hypercalcemia.
■Symptomatic patients with severely elevated calcium levels often require profound fluid volume replacement, which makes outpatient therapy impractical and unsafe.
■Mild asymptomatic hypercalcemia with serum calcium concentration in the range of 11 to 12 mg/dL should be treated, when there is associated hypercalciuria, because of the risk of nephrolithiasis and nephrocalcinosis.
Practical Management
■Immediate administration of isotonic saline (1 to 2 L over 1 hour followed by 300 to 400 mL per hour, unless the patient has heart failure or renal failure) to increase renal blood flow and calcium excretion.
■Once rehydration is complete and urinary output is optimized, the need for bisphosphonate administration should be assumed.
■IV zoledronic acid (4 mg IV, infused over at least 15 minutes) is commonly used in malignancy-induced hypercalcemia. Usually a single dose is adequate, when used to treat hypercalcemia.
■Bisphosphonate administration is well tolerated by patients except for occasional IV site irritation and fever during infusion. Its onset of action is within 24 to 48 hours of administration; the maximal effect may not be achieved until 72 hours after treatment.
■Dose should only be repeated after at least 7 days.
■The ASCO guidelines for bisphosphonate use in myeloma recommend that for zoledronic acid,
•Creatinine clearance >60 mL per minute; no dosing changes are required.
•Creatinine clearance >30 mL per minute and <60 mL per minute; dose should be reduced (follow package insert).
•Creatinine clearance <30 mL per minute contraindicated.
■Denosumab inhibits osteoclast development, activation, and survival by preventing the receptor activator of nuclear factor-kappa B ligand and has been used to treat bisphosphonate refractory hypercalcemia. In meta-analysis of over 5,000 patients there was an increased incidence of hypocalcemia in the denosumab group; grade 3 or 4 laboratory abnormalities for hypocalcemia were 88 (3.1%) for the denosumab group and 38 (1.3%) for the zoledronic acid group. In addition, denosumab is safe to be used in patients with renal failure and could be effective in bisphosphonate refractory patients.
■Denosumab should be the preferred agent in patients with creatinine clearance <30 mL per minute.
■Depending on clinical urgency, dental evaluation must be obtained before bisphosphonates are initiated to prevent osteonecrosis of the jaw.
■Osteonecrosis of the jaw is a potentially devastating complication of bisphosphonate and RANKL inhibitor use, and is associated with poor dentition. Among bisphosphonates use, jaw osteonecrosis rates are higher among myeloma patients. Patients with multiple myeloma had a rate 4.5 times that of patients with breast cancer in one study.
■Corticosteroids can be considered in select patients and is often effective. These tumors include lymphoma, leukemia, myeloma (prednisone, 40 to –100 mg per day), and breast cancers (prednisone, 15 to 30 mg per day) during hormonal therapy.
■Calcitonin has a rapid onset of action (within 4 hours) and is often useful in severe and symptomatic hypercalcemia until the more slowly acting agents become effective (e.g., zoledronic acid, pamidronate, and gallium nitrate).
■Salmon calcitonin is initially given at 4 units per kg (body weight) SC or IM every 12 hours. If response is not satisfactory after 1 to 2 days, the dosage may be increased to 8 units per kg SC or IM every 12 hours. If response is still not adequate after a 1- to 2-day trial at the higher dose, the dosing interval should be decreased to 8 units per kg SC or IM every 6 hours. Although many patients initially will respond to calcitonin, tachyphylaxis often develops rapidly, which renders patients refractory to its hypocalcemic effect.
■Hemodialysis should be considered, in addition to the other treatments listed for hypercalcemia, in patients who have serum calcium level in the range of 18 to 20 mg/dL and/or in those who have neurologic symptoms but are hemodynamically stable.
■Galium nitrate and mithramycin have been found to be useful in the treatment of malignancy associated hypercalcemia.
■Treatment of hypercalcemia of malignancy is summarized in Table 36.3.
TUMOR LYSIS SYNDROME
Tumor lysis syndrome (TLS) occurs when cellular disruption results in life-threatening lactic acidosis, with concomitant hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia.
Etiology
■Tumor lysis can occur before the start of treatment (primary TLS) or more commonly after the administration of highly effective therapy (secondary TLS). The risk of developing TLS depends on multiple factors such as disease burden and preexisting nephropathy. In one study, for AML patients, tumor lysis was the major cause of death in 2% of cases.
Clinical Setting, Signs, and Symptoms
■TLS typically occurs in patients with acute leukemias (AML and ALL) with high white cell count, though it can also occur in patients with lymphomas (particularly Burkitt lymphoma) and solid tumors that are sensitive to therapy.
■TLS can be classified as laboratory TLS and clinical TLS. Laboratory TLS is defined as two or more abnormal values of uric acid, potassium, phosphorus, or calcium at presentation or a 25% change from baseline.
■Clinical TLS is defined as laboratory TLS accompanied with seizures, cardiac arrythmias, renal dysfunction, or sudden death.
■These criteria must be met 3 days before and up to 7 days after the initiation of therapy.
■Clinical index of suspicion should be high, as onset of TLS could be insidious. Cardiac arrhythmias may result from the severe hyperkalemia or hypocalcemia that accompanies the TLS. Hypocalcemia can result in tetany, whereas hyperphosphatemia and hyperuricemia can result in acute renal failure (ARF).
Management
Main Principles
■Identification of high-risk patients with initiation of preventive therapy.
■Early recognition of metabolic and renal complications with prompt supportive care, including hemodialysis.
Prevention and Treatment (Table 36.4)
■Preventive measures include the identification of individuals at risk; 24 to 48 hours of vigorous pretreatment volume expansion (3,000 mL/m2/day), use of pretherapeutic allopurinol (300 to 600 mg, PO q day), and vigilant metabolic monitoring (every 3- to 4-hour laboratory tests) after institution of therapy. These actions are the hallmarks of TLS prevention and management. Elevated levels of lactate dehydrogenase (LDH), uric acid, or creatinine at presentation identify a particularly high-risk patient.
■Rasburicase is a recombinant urate oxidase that catalyzes enzymatic oxidation of poorly soluble uric acid into an inactive and more soluble metabolite (allantoin). It can be given as a single dose between 3 mg and 7.5 mg. The manufacturer suggested dose is 0.2 mg/kg as an IV infusion over 30 minutes. Usually a single dose is adequate, though as per the manufacturer up to five doses can be administered.
■Rasburicase enzymatically degrades uric acid in blood samples left at room temperature. Blood should be collected in prechilled tubes containing heparin, transported in an ice bath, and assayed within 4 hours.
■Rasburicase should not be administered to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
HYPERPHOSPHATEMIA
■In mild hyperphosphatemia, dietary phosphate is restricted to 0.6 to 0.9 g per day, and an oral phosphate binder such as calcium carbonate is added. Severe hyperphosphatemia with symptomatic hypocalcemia can be life-threatening.
■The hyperphosphatemia usually resolves within 6 to 12 hours if renal function is intact.
■Phosphate excretion can be increased by saline infusion, although this can further reduce the serum calcium concentration by dilution.
■Phosphate excretion can also be increased by administration of acetazolamide (15 mg/kg every 3 to 4 hours).
■Hemodialysis is often indicated in patients with symptomatic hypocalcemia, particularly if renal function is impaired.
HYPOCALCEMIA
■The most appropriate treatment of hypocalcemia, in the absence of hypomagnesemia, is IV calcium, at a dose of 100 to 200 mg of elemental calcium (1 to 2 g of calcium gluconate) in 10 to 20 minutes.
■Such infusions do not raise the serum calcium concentration for more than 2 to 3 hours and, therefore, should be followed by a slow infusion of 10% calcium gluconate (90 mg of elemental calcium per 10 mL ampule) at the rate of 0.5 to 1.5 mg/kg IV per hour.
■Calcium chloride, 10% (272 mg of elemental calcium per 10 mL ampule), can also be used, with 5 to 10 mL given initially IV slowly over 10 minutes or diluted in 100 mL of 5% dextrose in water and infused over 20 minutes. This dosage should be repeated as often as every 20 minutes if the patient is symptomatic. Serum calcium levels should be monitored every 4 to 6 hours and hypomagnesemia be corrected as needed.
■Primary management of the hyperphosphatemia is critical to minimize metastatic deposition of insoluble calcium phosphate. Hemodialysis is almost always required by this time.
HYPERKALEMIA
■Psuedohyperkalemia can occur in the setting of extreme hyperleukocytosis, most commonly with chronic lymphocytic leukemia. This has been attributed to use of vacuum tubes and pneumatic tube transport, which may directly lyse the fragile malignant WBCs, releasing potassium. Aspiration of blood gently into a syringe without shaking and gently transporting the sample to the laboratory might correct the artifact.
■If the patient is asymptomatic, with a plasma potassium concentration of 6.5 mEq/L and with an ECG that does not manifest signs of hyperkalemia, then withhold potassium and initiate the administration of cation exchange resins.
■If the patient is symptomatic, with peripheral neuromuscular weakness, electrocardiographic signs of hyperkalemia, or plasma potassium concentration above 7 mEq/L, consider calcium gluconate, 10% solution, 10 mL IV given over 2 to 5 minutes (dose can be repeated after 5 minutes if electrocardiographic changes persist), followed by glucose with insulin, sodium bicarbonate, or a nebulized β-agonist. Prepare for hemodialysis.
■Measures to reduce serum potassium level:
•Regular insulin, 10 units plus 50% glucose, 50 mL IV as a bolus (onset 15 to 60 minutes; duration 4 to 6 hours), followed by glucose infusion to prevent hypoglycemia. Insulin along with glucose lowers the potassium level by driving it into the cell.
•Adrenergic β2-agonist, such as nebulized albuterol, 10 to 20 mg in 4 mL normal saline, inhaled over 10 minutes (onset 15 to 30 minutes; duration 2 to 4 hours), is effective in reducing serum potassium concentration. Adrenergic β2-agonists induce hypokalemia by stimulating the transport of potassium into skeletal muscle.
•Sodium bicarbonate, at the dose of 45 mEq (1 ampule of a 7.5% sodium bicarbonate solution), is infused slowly over 5 minutes (onset 30 to 60 minutes; duration several hours); this dose can be repeated in 30 minutes if necessary. This also temporarily drives the potassium inside the cell.
•Kayexalate, orally or rectally, 15 to 50 g in 50 to 100 mL of 20% sorbitol solution, is repeated every 3 to 4 hours, as needed, for up to 5 times per day (onset, 1 to 3 hours, duration of several hours).
•Minimize administration of drugs that can cause or potentiate hyperkalemia (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs], β-blockers, angiotensin-converting enzyme [ACE] inhibitors, and potassium-sparing diuretics).
HYPERURICEMIA AND RENAL FAILURE
■Hyperuricemic ARF following chemotherapy may be avoided by (a) prechemotherapeutic identification of patients at risk for developing TLS and (b) administration of allopurinol at doses of 600 to 900 mg every day, starting several days before chemotherapy, with tapering doses to maintain uric acid levels of <7 mg/dL.
■The therapy for hyperuricemic ARF before chemotherapy consists of administering allopurinol (if it has not already been given) and attempting to wash out the obstructing uric acid crystals by a loop diuretic and by fluids. Sodium bicarbonate should not be given at this time because it is difficult to raise the urine pH in this setting. Hemodialysis to remove the excess circulating uric acid should be used in patients in whom a diuresis cannot be induced.
■Rasburicase can be used at 3 to 7.5 mg as a single dose for the rapid correction of hyperuricemia. It can also be used prophylactically, prior to the initiation of definitive therapy to underlying malignancy, for high-risk tumors, that is, ALL and AML.
■Hyperuricemic ARF following chemotherapy is usually refractory to conservative intervention (hydration, diuretics, etc.), and patients require hemodialysis for supportive therapy and renal recovery.
REVIEW QUESTIONS
1.A 62-year-old male recently diagnosed with IgA kappa multiple myeloma presents with new onset pain in his lower back, muscle weakness, and sensory loss along his lower extremities. His symptoms are consistent with SCC. All of the following statements are accurate about SCC except for
A.SCC most often involves the lumbosacral spine.
B.The three most common underlying cancer diagnoses associated with SCC are lung cancer, breast cancer, and multiple myeloma.
C.Pain is usually the first symptom of SCC, often worse with recumbency.
D.MRI of the entire thecal sac is the preferred modality for initial evaluation of a patient with suspected SCC.
E.The most important prognostic factor for regaining ambulation after treatment of SCC is pretreatment neurologic status.
2.A 29-year-old man presents with new onset dyspnea and dysphagia. On physical examination, he has left-sided facial edema and venous distension of the neck and chest wall. He does not have stridor or mental status changes. CT with contrast of the neck and chest reveals bilateral cervical lymphadenopathy, a 10 cm anterior mediastinal mass compressing the SVC. What is the next best step?
A.Immediate radiation oncology consult for RT to the affected area.
B.Start the patient on glucocorticoids and chemotherapy.
C.Consider thrombolytic therapy and subsequent anticoagulation.
D.Endovascular stenting followed by excisional biopsy of the cervical lymph node.
3.An 83-year-old man presents to the emergency room with 1-week history of generalized weakness and progressive change in mental status. He was found confused at his apartment, by his son. He has a history of diabetes and renal failure, which is well controlled. Labs in the emergency room show serum calcium of 14 mg/dL. His albumin is 3 mg/dL. Serum creatinine is 3 mg/dL. Chest x-ray shows a left upper lobe mass lesion.
Which of the following statements is/are correct?
A.He should receive an immediate dose of zolendronic acid 4 mg, given over 15 minutes.
B.He should be adequately hydrated prior to giving zolendronic acid.
C.Denosumab might be a better alternative, to correct his hypercalcemia.
D.His calcium levels should be closely monitored, if he is treated with denosumab to assess for hypocalcemia.
E.Osteonecrosis of jaw seldom occurs with denosumab.
F.A and B.
G.B and D.
H.B, C, and D.
4.A 34-year-old man is being treated with chemotherapy for acute myeloid leukemia. You are called to evaluate the patient, late at night, as he has become somnolent and is not waking up. At presentation, 24 hours ago his white blood cell count (WBC) was 160,000/L with 80% myeloblasts; the hemoglobin was 7.5 g/dL, and platelet count was 10,000/L. His electrolytes and renal function are normal. His uric acid is 11.0 mg/dL, and LDH is 1,000 international units/L (normal, 100 to 250 international units/L). His phosphate levels are 2 mmol/L.
Which of the following statements is/are true?
A.A diagnosis of TLS has to be considered.
B.Rasburicase is a synthetic urate oxidase agonist that is indicated for the treatment of hyperuricemia in patients with TLS.
C.A single dose of rasburicase between 3 and 7.5 mg has been shown to be as effective as weight-based dosing.
D.Blood samples have to be collected in prechilled tubes and transported on ice to avoid spuriously low values of uric acid in patients being treated with rasburicase.
E.For patients suspected to have or at high risk for TLS, hydration with 4 to 5 L of IV fluids, 48 hours before induction chemotherapy, and maintaining a urine output of at least 80 to 100 mL/m2 per hour is indicated.
F.All the above.
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