Optimal Timing Optimal Administration of Colony-Stimulating Factors
15.3 Erythropoietin
Erythropoietin EPO is a sialoglycoprotein pro- duced primarily in the cortical region of the kid- neys. EPO stimulates the proliferation and terminal differentiation of erythroid precursors in the bone marrow and is specifi cally stimulated by hypoxic conditions Krantz 1991 ; Jelkmann 1992 . In addition to effects on proliferation and differentiation, EPO has been shown to modulate apoptosis and increase erythrocyte survival time Masuda et al. 1999 . Additional studies have shown that EPO stimulates the proliferation and migration of endothelial cells in vitro and stimu- lates the expression of other angiogenic growth factors including vascular endothelial growth factor VEGF and placental growth factor Batra et al. 2003 . Recombinant human erythropoietin rhEPO was fi rst approved in 1989 for the treat- ment of anemia associated with chronic kidney disease and subsequently approved for the treat- ment of chemotherapy-induced anemia in patients with nonmyeloid malignancies. A second EPO-stimulating agent ESA, darbepoetin alfa, which has a 2–3-fold half-life compared with rhEPO, is also approved by the FDA for adult patients Zamboni and Stewart 2002 . Darbepoetin has undergone a phase I trial in pediatric patients with chemotherapy-induced anemia but is not approved in this population Blumer et al. 2007 . Multiple adult randomized controlled trials have shown that ESAs increase hemoglobin, reduce red blood cell transfusion requirements and improve quality of life in patients with che- motherapy- or radiation therapy-associated ane- mia Bokemeyer 2004 ; Bohlius et al. 2006 . Very limited data exist for pediatric oncology patients and has most recently been summarized by Shankar 2008 Porter et al. 1996 ; Csáki et al. 1998 ; Büyükpamukçu et al 2002 ; Wagner et al. 2004 ; Yilmaz et al. 2004 ; Razzouk et al. 2006 ; Abdelrazik and Fouda 2007 ; Çorapcioglu et al. 2008 ; Durmaz et al. 2011 . These studies are gen- erally with small cohorts of patients with a mix- ture of different pediatric malignancies and utilize variable doses, dose schedules, and routes of administration for rhEPO. The studies all show increased hemoglobin and decreased transfusion requirement as compared to controls. Quality of life data are limited, with only a subset of patients in the largest study showing signifi cant improve- ment Razzouk et al. 2006 . Data of effect on overall survival between the two groups are not ascertainable due to the small cohorts studied and was only reported in two studies Wagner et al. 2004 ; Durmaz et al. 2011 . Two adult trials of rhEPO in breast and head and neck cancer reported in 2003 were concerning for increased mortality rates and increased dis- ease recurrence in the rhEPO treatment arm as compared to controls Henke et al. 2003 ; Leyland-Jones 2003 . Since that time, multiple meta-analyses have shown that survival may be worsened by utilization of ESAs, possibly sec- ondary to an increased risk of thromboembolic events which may be related to a high hemoglo- bin goal with rhEPO therapy Bohlius et al. 2006 ; Bennett et al. 2008 ; Bohlius et al. 2009 , 2010 ; Glasby et al. 2010 . No pediatric study has reported any case of venous thromboembolism secondary to rhEPO. Concern has also been raised due to the promotion of angiogenic growth factors and expression of antiapoptotic genes by EPO and potential effect on tumor cell growth Batra et al. 2003 ; Yasuda et al. 2003 . Batra et al. 2003 additionally reported the presence of EPO receptors and expression of EPO on pediatric tumor cells including neuroblastoma, Ewing sar- coma, Wilms tumor, rhabdomyosarcoma, hepato- blastoma, medulloblastoma, ependymoma and astrocytoma. Sartelet et al. 2007 similarly reported increased EPO-R expression on neuro- blastoma cell lines, although in vitro they were unable to show increased tumor cell proliferation with exogenous EPO. No study has shown an in vivo effect of ESAs on tumor proliferation and in a recent review Aapro et al. 2012 conclude that current clinical and preclinical data have not shown that ESAs have an effect on disease progression. Updated 2010 ASHASCO guidelines as well as the 2010 ESMO guidelines on the use of ESAs in adult oncology patients recommend a careful weighing of the risks and potential benefi ts of ESA therapy in patients with hemoglobin 10 g dL and nonmyeloid malignancies Rizzo et al. 2010 ; Schrijvers et al. 2010 . Concerns remain in regard to the stimulation of the leukemic clone and therefore ESAs are not recommended in leu- kemia, especially acute myelogenous leukemia Takeshita et al. 2000 . The combined guidelines recommend that ESAs should be used only in patients currently undergoing chemotherapy and should be used cautiously in patients undergoing therapy with curative intent and in those with risk for thromboembolism Rizzo et al. 2010 ; Schrijvers et al. 2010 . Additionally, patients should be monitored and treated for other etiolo- gies of anemia such as iron defi ciency and also monitored to ensure that hemoglobin does not increase over 12 gdL Glaspy and Cavill 1999 ; Rizzo et al. 2010 ; Schrijvers et al. 2010 . With the paucity of reported data, similar such guidelines are unavailable in the pediatric literature. For pediatric patients, the French National Cancer Institute concluded that: 1 systematic adminis- tration of ESAs is not recommended in pediatric cancer patients with anemia, 2 ESAs can be con- sidered on a case-by-case basis in those patients with a contraindication to red blood cell transfu- sion, and 3 intravenous ESA use is the preferred method of administration Marec-Berard et al. 2009 . From the adult oncology literature it is unclear if there is potency difference between subcutaneous and intravenous rhEPO administra- tion although studies in adult hemodialysis patients have shown that subcutaneous injection is approximately 30 more effective Kaufman et al. 1998 ; Galliford et al. 2005 ; Vercaigne et al. 2005 . In his editorial response to the French guidelines, Feusner 2009 concurs that evidence is lacking to support ESA use in pediatric oncol- ogy patients as their benefi t in quality of life and cost-effectiveness in this patient population as well as their potential risks in regard to tumor pro- gression, overall survival and thromboembolism are unclear.15.4 Platelet Growth Factors
Platelet transfusion remains the only method for treatment of clinically signifi cant thrombocytope- nia in pediatric oncology patients. Multiple growth factors have in vitro stimulatory effects on platelet production, but only IL-11, stem cell fac- tor and thrombopoietin TPO have shown in vivo benefi t Broudy et al. 1995 ; Kuter et al. 1999 ; Kaushansky 2005 ; Bhatia et al. 2007 ; Zeuner et al. 2007 . Only IL-11 is approved for chemotherapy-induced thrombocytopenia and only in adult patients. TPO-receptor antagonists have been approved for the treatment of adult immune thrombocytopenic purpura ITP but asParts
» 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
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