Laboratory Risk Factors Supportive Care in Pediatric Oncology irantextbook.ir 93df

3.3 General Management

Guidelines Prevention is the key component of TLS manage- ment in high-risk patients and hyperhydration i.e., 3 Lm 2 day is the most important prophy- lactic intervention although randomized evidence supporting its benefi t is lacking due to the risk of withholding such therapy in high-risk patients Table 3.3 Coiffi er et al. 2008 ; Tosi et al. 2008 . Intravenous fl uids should ideally be started 24 h prior to the initiation of cytotoxic therapy. Fluid status must be monitored vigilantly taking into account the patient’s daily fl uid balance, urine output, laboratory evidence of renal function and physical exam evidence of fl uid overload i.e., change in weight, edema, dyspnea, rales or gal- lop rhythm. Dilute urine output, defi ned as 100 mlm 2 h 4 mlkgh for infants with a urine specifi c gravity 1.010, should be estab- lished prior to the initiation of chemotherapy and should be maintained at such levels during the acute phase of therapy Coiffi er et al. 2008 ; Tosi et al. 2008 . Loop diuretics and mannitol can be utilized to maintain good urine output but should be avoided in patients with evidence of hypovole- mia Coiffi er et al. 2008 ; Tosi et al. 2008 . Frequent laboratory monitoring is necessary to assess for evidence of LTLS and risk of CTLS. Uric acid, phosphate, potassium, calcium and creatinine levels should be checked prior to the initiation of cytoreductive therapy. The frequency of monitor- ing thereafter must be tailored to each individual patient and may be required as often as every 4–6 h in patients exhibiting signifi cant LTLS worrisome for the development of CTLS or as infrequently as every 24 h in lower- risk patients Coiffi er et al. 2008 ; Tosi et al. 2008 . Guidelines recommend fol- lowing LDH levels as a marker of decreasing tumor burden and TLS risk although it is unclear if this is really necessary to appropriately assess the patient Coiffi er et al. 2008 ; Tosi et al. 2008 . In addition, patients who develop hyperkalemia and hyper- phosphatemia or who have poor urine output despite vigorous hydration should undergo renal ultrasound to rule out renal parenchymal involve- ment or obstructive uropathy. Electrocardiographic ECG monitoring may be warranted if the patient has either hyperkalemia i.e., potassium ≥6 mEqL or hypocalcemia Table 3.2 Risk factor stratifi cation for clinically signifi cant tumor lysis syndrome at disease presentation in pediatric patients a High risk for CTLS Stage IIIIV Burkitt lymphoma with LDH ≥2× ULN andor bulky retroperitoneal disease ALL with WBC ≥200 × 10 9 L and uric acid ≥11.0 mgdL b Hyperphosphatemia Hypocalcemia Hyperkalemia Oliguria Renal involvement in leukemia or lymphoma Low risk for CTLS Non-lymphomatous solid tumors Hodgkin lymphoma Chronic myelogenous leukemia Acute myelogenous leukemia Stage III NHL ALL in children 10 years of age with WBC 20 × 10 9 L and no mediastinal mass or splenomegaly Intermediate risk for CTLS All others not classifi ed as low or high risk CTLS clinical tumor lysis syndrome, LDH lactate dehydrogenase, ULN upper limit of normal, ALL acute lymphoblastic leukemia, WBC white blood cell, LTLS laboratory tumor lysis syndrome, NHL non-Hodgkin lymphoma a See text for detail, level of evidence 1B for all categorizations per Guyatt et al. [2006]; see Preface b WBC 25 × 10 9 L or LDH ≥2× ULN without LTLS is not a risk factor for TLS in ALL patients A. Marsh et al. Table 3.3 Pharmacologic interventions for the treatment of tumor lysis syndrome a Condition Level of evidence b General management Intravenous fl uids D5W 12NS infused at 3 Lm 2 day without potassium or calcium 1C Sodium bicarbonate 20–40 mEqL if the patient has HU or risk for HU; can decrease to 14NS if on 40 mEqL or more of sodium bicarbonate 2C Urinary alkalinization not required if utilizing rasburicase 1B Urinary alkalinization should not be initiated with concomitant hyperphosphatemia 1A Laboratory monitoring Monitor potassium, phosphorus, calcium, uric acid, BUNcreatinine every 4–6 h in patients at high risk for tumor lysis 1C Can wean labs to every 12–24 h as tumor burden decreases over 3–7 days 1C Hyperuricemia Allopurinol c 1B In all patients not receiving rasburicase; unclear evidence in low-risk patients 10 mgkgday PO divided Q8h to a maximum of 800 mgday Rasburicase d 1B Rasburicase prophylaxis should be limited to patients with evidence- based risk factors see Table 3.2 ; specifi cally stage IIIIV BL patients with elevated LDH ≥2× ULN andor bulky retroperitoneal disease, hyperleukocytic ALL WBC ≥ 200 × 10 9 L with severe hyperuricemia uric acid ≥11.0 mgdL or hyperuricemia not improving with hyperhydration, urinary alkalinization and allopurinol alone 0.03–0.05 mgkg IV × 1; subsequent doses not usually required but can be given if uric acid again 8 mgdL in high-risk patients Hyperphosphatemia Aluminum hydroxide 1C Avoid in patients with renal insuffi ciency Children: 50–150 mgkgday PO divided Q4–6 h Adolescents: 300–600 mg PO TID Sevelamer 1C Administer with each meal Children: dosing not well established Adolescent dosing based on phosphorus level mgdL: 5.5 and 7.5: 800 mg PO TID ≥7.5 and 9: 1200 mg PO TID ≥9: 1600 mg PO TID Calcium carbonate use with caution as can increase calcium-phosphate product and risk for calcium phosphate precipitation 1C Children: 30–40 mgkgdose with each meal Adolescents: 1–2 g with each meal Hyperkalemia Calcium gluconate, 100–200 mgkg IV slow infusion with ECG monitoring 1C Sodium polystyrene sulfonate, 1 gkg in 50 sorbitol PO Q6h max dose 15 g 1C Regular insulin + D25W, 0.1 unitkg insulin max 10 units + 2 mlkg 0.5 gkg D25W IV over 30 min 1C Albuterol 1C Inhaled via nebulizer 25 kg: 2.5 mg Inhaled via nebulizer 25–50 kg: 5 mg Inhaled via nebulizer 50 kg: 10 mg 3 Tumor Lysis Syndrome