Alkalinization Urinary alkalinization has been a long-standing
3.4.1.2 Allopurinol Allopurinol inhibits xanthine oxidase, an enzyme
which converts hypoxanthine and xanthine to uric acid. Krakoff and Meyer 1965 and DeConti and Calabresi 1966 fi rst showed that allopuri- nol effectively reduced serum uric acid levels without leading to signifi cant accumulation of xanthine and hypoxanthine due to differential solubility products. Allopurinol has been noted to be quite safe and is extremely inexpensive. Xanthine nephropathy secondary to TLS and leading to AKI with concomitant allopurinol has been rarely reported in the literature Band et al. 1970 ; Hande et al. 1981 ; Andreoli et al. 1986 ; Potter and Silvidi 1987 ; LaRosa et al. 2007 . Andreoli et al. 1986 reported that although xan- thine exceeded its solubility limit in 16 of 19 children with ALL receiving allopurinol, only 8 were noted to have precipitated xanthine in urine sediment and only half of those children devel- oped AKI. They therefore theorized that addi- tional factors are involved in the development of AKI during TLS. Xanthine nephropathy should be considered in the patient with AKI but appro- priate TLS prophylaxis; in such cases allopurinol should be reduced or discontinued, xanthine levels should be drawn and patients should be tested for a defect in the hypoxanthine- guanine phosphoribosyl trans ferase HGPRT enzyme LaRosa et al. 2007 . Drawbacks to allopurinol include a relatively slow onset of action i.e., 24–72 h, the neces- sity of dose reduction in the setting of renal insuffi ciency and its inability to degrade preex- isting uric acid Howard et al. 2011 . Intravenous allopurinol has been shown to be equally effec- tive and safe as compared to oral allopurinol but comes at a much higher cost 2,000-fold Smalley et al. 2000 ; Feusner and Farber 2001 ; Patel et al. 2012 . Prior to the advent of rasburi- case, intravenous allopurinol was a potential option in patients unable to tolerate oral intake but is no longer available in Europe Feusner and Farber 2001 ; Will and Tholouli 2011 . Utilizing a single low dose of rasburicase, Patel et al. 2012 were able to extrapolate a signifi - cant cost savings over intravenous allopurinol. Consensus guidelines recommend allopurinol in low- and intermediate- risk patients i.e., those patients not recommended to receive rasburi- case Coiffi er et al. 2008 ; Pession et al. 2011 . Consensus guidelines recommend that patients who receive rasburicase should only have allo- purinol initiated after rasburicase discontinua- tion in order to inhibit additional uric acid formation until the tumor burden is signifi cantly decreased i.e., usually 3–7 total days Coiffi er et al. 2008 ; Tosi et al. 2008 . Given the slow onset of action for allopurinol it may be more prudent to initiate allopurinol prior to this rec- ommended time point. Similar to urine alkalini- zation, it is unclear if the addition of allopurinol is benefi cial in patients with a low tumor burden and low risk of developing HU Table 3.3 Pession et al. 2011 .3.4.1.3 Rasburicase Rasburicase, recombinant urate oxidase, converts
uric acid into allantoin, a fi ve to ten times more soluble compound, in an extremely effective manner. Due to this fact, many studies have shown that rasburicase is effi cacious in correct- ing HU in pediatric and adult patients Pui et al. 2001 ; Patte et al. 2002 ; Bosly et al. 2003 ; Coiffi er et al. 2003 ; Jeha et al. 2005 ; Pession et al. 2005 ; Shin et al. 2006 ; Kikuchi et al. 2009 . Follow-up studies comparing effi cacy of rasburicase and allopurinol naturally show that rasburicase is much more effective in rapidly and dramatically reducing the uric acid level although such studies fail to incorporate a clinically relevant endpoint Goldman et al. 2001 ; Cortes et al. 2010 . Many of these studies were supported by the pharma- ceutical maker of rasburicase, including grant support, providing the drug, logistic support, edi- torial support, and data management, and some study authors had a fi nancial stake in the pharma- ceutical company Goldman et al. 2001 ; Pui et al. 2001 ; Patte et al. 2002 ; Bosly et al. 2003 ; Coiffi er et al. 2003 ; Jeha et al. 2005 ; Shin et al. 2006 ; Kikuchi et al. 2009 ; Cortes et al. 2010 . Early studies also utilized higher doses of rasburicase i.e., 0.15–0.2 mgkgday and for a longer dura- tion up to 7 days based on the recommendation of the manufacturer and what was approved by the United States Food and Drug Administration [FDA], rather than what is more rational based on the mechanism of the drug and underlying dis- ease process Pui et al. 2001 ; Patte et al. 2002 ; Bosly et al. 2003 ; Coiffi er et al. 2003 ; Jeha et al. 2005 ; Pession et al. 2005 ; Shin et al. 2006 ; Kikuchi et al. 2009 . Rasburicase doses as low as 0.017 mgkg as a single dose have subsequently been found effec- tive; many studies have shown that abbreviated rasburicase schedules are suffi cient Hummel et al. 2003 ; Lee et al. 2003 ; Liu et al. 2005 ; Ho et al. 2006 ; Hutcherson et al. 2006 ; McDonnell et al. 2006 ; Trifi lio et al. 2006 ; Reeves and Bestul 2008 ; Campara et al. 2009 ; Giraldez and Puto 2010 ; Vadhan-Raj et al. 2012 . Hummel et al. 2007 were able to utilize a low-dosing schedule resulting in an average decrease in uric acid lev- els by 83 while utilizing a median total dose of rasburicase of 0.049 mgkg, resulting in a cost reduction of 96.8 based on manufacturer dos- ing recommendations. Adult patients with initial average hyperuricemia of 13.1 mgdL were able to achieve uric acid 8.0 mgdL with an average single rasburicase dose of 0.032 mgkg Hummel et al. 2007 . Knoebel et al. 2011 similarly showed that most adult patients could be effec- tively treated with a single 0.05 mgkg dose. Yet, recent consensus guidelines still recommend a range of 1–7 days of rasburicase at a dose of 0.1–0.2 mgkgdose Coiffi er et al. 2008 ; Tosi et al. 2008 ; Pession et al. 2011 . Although gener- ally safe, rasburicase must be avoided in patients with glucose-6-phosphate dehydrogenase G6PD defi ciency and methemoglobinemia, and hemolytic anemia has been reported in childhood ALL Bauters et al. 2011 . Even though HU is a factor in LTLS, data are less clear that rasburicase is more effective in the prevention of CTLS than allopurinol. In their analysis of BFM data, Wössmann et al. 2003 compared LTLS and anuria risk in pediatric ALL and stage IIIIV BL patients with LDH ≥500 UL treated with either allopurinol or rasburicase; they found that although ALL patients treated with rasburicase had a trend toward decreased LTLS, it was not clinically signifi cant although there was a signifi cant decrease in the incidence of anuria. LTLS or anuria risk in children with BL was not signifi cantly different between rasbu- ricase and allopurinol Wössmann et al. 2003 . Despite decreasing uric acid levels, Ahn et al. 2011 noted no statistical difference in LTLS, CTLS or need for renal dialysis with rasburicase compared with allopurinol. A Cochrane review of rasburicase for the prevention and treatment of TLS in children with cancer similarly showed signifi cant reduction in uric acid levels, but the relevant analyzed studies failed to show that this equated to a signifi cant reduction in clinically signifi cant endpoints, specifi cally renal failure and mortality Cheuk et al. 2010 . Rasburicase remains an extremely expensive drug 535 per 1.5 mg vial compared to allopu- rinol and therefore it is vital to appropriately select patients that would benefi t from rasburi- case through the prevention of CTLS GoldmanParts
» Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Introduction Supportive Care in Pediatric Oncology irantextbook.ir 93df
» History and Physical Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Defi ning the Risk for Serious
» Initial Laboratory Evaluation Diagnostic Evaluation
» Chest Radiography CXR A supine CXR may identify pleural effusions,
» Computed Tomography CT Radiographic Imaging
» Magnetic Resonance Imaging MRI
» Positron Emission Tomography PET
» Aspergillus Galactomannan GMN Biomarkers for Invasive
» 1,3-β- Biomarkers for Invasive
» Polymerase Chain Reaction PCR
» Viral Studies Diagnostic Evaluation
» Invasive Procedures: Diagnostic Evaluation
» Adult FN Guidelines Empiric Management
» Monotherapy Versus Combination Therapy
» Which Monotherapy to Choose A Cochrane review of antipseudomonal beta-
» Alterations in Initial Empiric FN Antibiotic Management
» Outpatient Management of FN Although there remains a lack of one uniform
» Choice of Empiric Antifungal Therapy
» Duration of Antimicrobial Empiric Management
» Endovascular Sources Empiric Management
» Adjunctive Treatment Empiric Management
» Emergence of Resistant Empiric Management
» Red Blood Cell Administration
» Granulocyte Transfusion Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Hemolytic Transfusion Risks of Blood Product
» Infection and Sepsis Risks of Blood Product
» Allergic Reactions Risks of Blood Product
» Febrile Nonhemolytic Risks of Blood Product
» Transfusion-Related Acute Risks of Blood Product
» Transfusion-Associated Risks of Blood Product
» Iron Overload Risks of Blood Product
» Laboratory Risk Factors Supportive Care in Pediatric Oncology irantextbook.ir 93df
» General Management Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Alkalinization Urinary alkalinization has been a long-standing
» Allopurinol Allopurinol inhibits xanthine oxidase, an enzyme
» Rasburicase Rasburicase, recombinant urate oxidase, converts
» Renal Interventions Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Pathophysiology Superior Vena Cava
» History and Physical Exam SVCSSMS should be suspected in a patient
» Imaging Studies The diagnosis of SVCSSMS is often made on
» Other Studies Tissue is required to make a defi nitive diagnosis
» Treatment Superior Vena Cava
» History and Physical Exam Small pericardial effusions are frequently asymp-
» Imaging and Other Studies The presence of a pericardial effusion can be
» History and Physical Exam Many patients with small pleural effusions are
» Imaging Studies When a pleural effusion is suspected, a chest
» History and Physical Exam Patients with pheochromocytoma typically have
» Laboratory Studies The diagnosis of pheochromocytoma is best made
» Imaging Studies Clinical Presentation
» Pulmonary Leukostasis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Presentation Spinal Cord Compression
» Differential Diagnosis Spinal Cord Compression
» Imaging MRI of the spine can help narrow the differential
» Surgery Surgery in spinal cord compression can be uti-
» Radiation Therapy The advantages of external beam radiation ther-
» Outcomes Spinal Cord Compression
» Presentation Altered Mental Status
» Initial Management Altered Mental Status
» Metabolic The metabolic causes of AMS or seizure in pedi-
» Chemotherapy-Associated Neurotoxicity Differential Diagnosis
» Posterior Reversible Encephalopathy Syndrome
» Outcomes Altered Mental Status
» Initial Management Increased Intracranial
» Soft Tissue A large meta-analysis of published data suggests
» Cerebrospinal Fluid Hydrocephalus is an excess of CSF within the
» Hemorrhage and Thrombosis Differential Diagnosis
» Idiopathic Intracranial Hypertension Differential Diagnosis
» Presentation of Stroke Cerebrovascular Disease
» Differential Diagnosis Cerebrovascular Disease
» Etiology of Stroke in Pediatric
» Ischemic Stroke After an ischemic stroke is diagnosed, the patient
» Hemorrhagic Stroke Hematomas can expand over several hours from
» Acute Lymphoblastic Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Acute Myelogenous Leukemia Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Acute Promyelocytic Leukemia Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Chronic Myelogenous Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Management of Tumor Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Leukapheresis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Hyperhydration Other Treatment Modalities
» Hydroxyurea Other Treatment Modalities
» Cranial Irradiation Other Treatment Modalities
» Pseudohyperkalemia Hyperleukocytosis has been noted to cause pseudo-
» Pseudohypoxemia Due to the rapid consumption of oxygen by leu-
» Pseudohypoglycemia Consumption of glucose by excess leukocytes
» Pseudothrombocytosis Leukemic blast lysis can lead to cell fragmenta-
» Transfusion Practice with Other Supportive Care
» Anesthetic Procedures Other Supportive Care
» Neutropenic Enterocolitis Gastrointestinal Infection
» Perirectal Abscess Gastrointestinal Infection
» Gastrointestinal Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Pancreatitis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Bowel Obstruction Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Abdominal Compartment Supportive Care in Pediatric Oncology irantextbook.ir 93df
» ALL Risk Factors Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Other Malignancies Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Central Venous Catheters Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Diagnosis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Nociceptive Pain Types of Pain
» Neuropathic Pain Types of Pain
» World Health Organization Pharmacologic Treatment
» Intermittent Opioid Use Pharmacologic Treatment
» Long-Acting Opioids Pharmacologic Treatment
» Breakthrough Dosing Pharmacologic Treatment
» Opioid Rotation Pharmacologic Treatment
» Patient-Controlled Analgesia Pharmacologic Treatment
» Constipation Side Effects of Opioids
» Nausea and Vomiting Nausea and vomiting are rare opioid side effects
» Pruritus Pruritus is a common side effect of opioid use
» Sedation Side Effects of Opioids
» Confusion and Agitation Renal and hepatic function should be checked
» Respiratory Depression When dosed appropriately, opioids rarely result
» Myoclonus Patients receiving very high doses of opioids for
» Urinary Retention Urinary retention can be caused by any opioid but
» Calcium Channel Blockers Neuropathic Pain
» Serotonin and Norepinephrine Neuropathic Pain
» Tricyclic Antidepressants Neuropathic Pain
» Interventional Techniques Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Vincristine-Related Peripheral Oncology-Specifi c Pain
» Osteonecrosis Oncology-Specifi c Pain
» Post-lumbar Puncture Oncology-Specifi c Pain
» Mucositis Pain Oncology-Specifi c Pain
» Pathophysiology of Emesis Chemotherapy-Induced
» Principles of Emesis Control in the Cancer Patient
» Emetogenicity of Chemotherapy Chemotherapy-Induced
» Dopamine Receptor Antagonists Classes of Antiemetics
» Corticosteroids Classes of Antiemetics
» Cannabinoids The plant Cannabis contains more than 60 differ-
» Other Antiemetic Agents Antihistamines
» Alternative Therapies Ginger Classes of Antiemetics
» Management of CINV Management of CINV Table
» Special Considerations Anticipatory Nausea and Vomiting
» Radiation-Induced Nausea Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Initiation The initiation stage occurs immediately following
» Primary Damage Response Pathophysiology of Oral Mucositis
» Signal Amplifi cation Pathophysiology of Oral Mucositis
» Ulceration Ulceration is the phase with the most clinical sig-
» Healing Pathophysiology of Oral Mucositis
» Clinical Course of Oral Mucositis
» Assessment Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Palifermin Prevention and Treatment
» Low-Level Laser Therapy Prevention and Treatment
» Glutamine Prevention and Treatment
» Cryotherapy Prevention and Treatment
» Oral Care Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Oral Infections Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Nutrition Assessment Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Dietary Counseling Nutrition Intervention
» Appetite Stimulants Nutrition Intervention
» Enteral Tube Feeding Nutrition Intervention
» Parenteral Nutrition Nutrition Intervention
» Nutrition and Survivorship Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Management of Neutropenia Hematologic Toxicity
» Management of Thrombocytopenia Hematologic Toxicity
» Management of Anemia Hematologic Toxicity
» Somnolence Syndrome Central Nervous System
» Lhermitte’s Sign Central Nervous System
» Skin Complications Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Oral Mucositis Head and Neck
» Ear Complications Head and Neck
» Laryngeal Complications Head and Neck
» Dysphagia and Esophagitis Gastrointestinal
» Nausea, Vomiting and Anorexia
» Pneumonitis Major Organ Infl ammation
» Pericarditis Major Organ Infl ammation
» Hepatitis Major Organ Infl ammation
» Nephropathy Major Organ Infl ammation
» Cystitis Major Organ Infl ammation
» Risk Stratifi cation Prevention of Bacterial
» Adult Data Antimicrobial Approaches
» Pediatric Data Data regarding the utility of bacterial prophylaxis
» Risks of Prophylaxis Prevention of Bacterial
» Guidelines and Current Usage of Antibacterial Prophylaxis
» Protocols for Line Placement and Care
» Antibiotic and Ethanol Locks
» Chlorhexidine Cleansing Chlorhexidine gluconate CHG is a bactericidal
» Future Directions Prevention of Bacterial
» Risk Stratifi cation Prevention of Fungal
» Approaches to Antifungal Prophylaxis
» Guideline Recommendations for Antifungal Prophylaxis
» Limitations of Current Options for Antifungal Prophylaxis
» Risks of Prophylaxis Prevention of Fungal
» Biomarkers Prevention of Fungal
» Future Directions Prevention of Fungal
» Risk Stratifi cation Prevention of Pneumocystis
» Approaches to PCP Prophylaxis
» Summary of the Recommendations
» Future Directions Prevention of Pneumocystis
» Postexposure Chemoprophylaxis Prevention of Viral Infections
» Suppressive Therapy Prevention of Viral Infections
» Future Directions Prevention of Viral Infections
» Hand Hygiene Infection Control Practices
» Mandatory Vaccination Infection Control Practices
» Hospital Isolation Practices Infection Control Practices
» Visitor Screening Policies Infection Control Practices
» Work Restriction Infection Control Practices
» Cytomegalovirus CMV Status of Transfused Blood
» Treatment of Myelosuppression with
» Prevention of Febrile Neutropenia, Delay
» Treatment of Febrile Neutropenia
» Treatment of Myelosuppression Clinical Usage of Myeloid Growth Factors
» Comparison of Granulocyte Colony-Stimulating Factor
» Optimal Dosing Adult guidelines recommend dosing of 5 mcgkg
» Route of Administration Optimal Administration of Colony-Stimulating Factors
» Optimal Timing Optimal Administration of Colony-Stimulating Factors
» Erythropoietin Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Interleukin-11 Platelet Growth Factors
» Thrombopoietin Receptor Agonists Platelet Growth Factors
» Immune Status Prior Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Immune Status During Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Immune Recovery After Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Immunization Practice Prior Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Diphtheria, Tetanus, and Acellular Pertussis
» Pneumococcal Conjugate Vaccine Recommendations
» Hemophilus Infl uenzae Type b
» Inactivated Infl uenza Vaccine Although in a Cochrane review Goossen et al.
» 2009 H1N1 Pandemic Vaccine Seven studies have reported on effi cacy of the
» Live Attenuated Infl uenza Vaccine
» Meningococcal Conjugate Vaccine Recommendations
» Varicella Zoster Virus Recommendations
» Recommendations Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Treatment of Hypogammaglobulinemia Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Vaccination of Household Contacts
» Peripherally Inserted Central Catheter
» External Tunneled Central Venous Catheter
» Implanted Port Types of Central Venous
» Catheter Insertion Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Exit Site Infection Infection
» Prevention of Infection Infection
» Drug Precipitate or Lipid Residue Occlusion Thrombotic Occlusion
» Evaluation of Catheter- Related Thrombosis
» Treatment of Catheter- Related Thrombosis
» Special Considerations During Anticoagulation Therapy
» Contraindications of Anticoagulant Therapy
» Skin Antisepsis Catheter Maintenance
» Central Venous Catheter Dressings
» Hub Care Catheter Maintenance
» Central Venous Catheter Flushing and Locking
» Chlorhexidine Bathing Chlorhexidine has been shown to be effective in
» Antiseptic Needleless Connectors and Antiseptic
Show more