Treatment of Myelosuppression with
15.2.1.2 Prevention of Febrile Neutropenia, Delay
in Chemotherapy Delivery, or Dose Reduction Adult guidelines recommend consideration for CSFs in patients in which delay in chemotherapy delivery or dose reduction is known to be poten- tially harmful in treatment outcome Smith et al. 2006 ; ESMO 2007 ; Aapro et al. 2011 . Early phase I and II studies in adult patients have shown that reduction in chemotherapy delay can be achieved with G-CSF and GM-CSF Antman et al. 1988 ; Bronchud et al. 1989 . Pediatric data are unclear although the recently published improved survival in localized Ewing sarcoma patients who received compressed every 2-week therapy with G-CSF support as compared to the standard every 3-week arm implies there are situ- ations in which G-CSF may be benefi cial Womer et al. 2012 . Further data are required to make more generalized pediatric recommendations. As a corollary, G-CSF has been analyzed as a method to increase dose intensity since chemotherapeutic effect is directly related to the dose delivered Bonadonna and Valagussa 1981 ; Kwak et al. 1990 . Multiple pediatric studies have evaluated increased dose intensity with G-CSF support, and although these studies have shown the safety of this method, benefi t on outcome has not been delineated Woods et al. 1993 ; Kushner et al. 1994 ; White et al. 1994 ; Jones et al. 1995 ; Kushner et al. 1995 ; Michon et al. 1998 ; Fernandez et al. 2000 ; Kushner et al. 2000 ; Michel et al. 2000 ; Saarinen-Pihkala et al. 2000 ; Alonzo et al. 2002 . In the meta-analysis by Sasse et al. 2005 in pediatric ALL patients, CSF usage had no effect on chemotherapy delays.15.2.1.3 Treatment of Febrile Neutropenia
As described, adult consensus guidelines recom- mend utilization of CSFs in patients with high- risk neutropenia which is variably defi ned as neutropenia for 7–10 days, profound neutrope- nia with ANC 0.1 × 10 9 L, as well as clinical situations including pneumonia, hypotension, sepsis syndrome with multiorgan failure, uncon- trolled primary disease and invasive fungal infec- tion Smith et al. 2006 ; ESMO 2007 ; Aapro et al. 2011 . In a meta-analysis of randomized con- trolled trials, Clark et al. 2005 found that the use of CSFs in established febrile neutropenia reduced hospital stay and neutrophil recovery with potential marginal effect on infection- related mortality; no subgroup analysis on patients defi ned as high-risk could be performed. Limited data exist in pediatric patients: three ran- domized prospective trials have shown shortened median hospital stays, days of antibiotic use, cost of treatment and a reduction in duration of the febrile neutropenic episode Riikonen et al. 1994 ; Mitchell et al. 1997 ; Ozkaynak et al. 2005 . Pediatric consensus guidelines suggest similar parameters for utilization of CSFs in febrile neu- tropenia as adult guidelines, recommending usage in patients with pneumonia, hypotension, multiorgan dysfunction and fungal infection as well as, potentially, prolonged neutropenia i.e., 28 days, bacterial sepsis and age 12 months Schaison et al. 1998 ; Lehrnbecher and Welte 2002 . Although no pediatric study has demon- strated that CSF usage impacts infection- related mortality, reduction in hospital stay and therefore cost are reasonable parameters to support CSF utilization, especially in the high-risk patient.15.2.1.4 Treatment of Myelosuppression
with Radiation Therapy Adult guidelines recommend avoidance of CSFs during concomitant radiation therapy to the mediastinum due to a noted increased risk of mortality Smith et al. 2006 ; ESMO 2007 . The ASCO guidelines also warn against the use of CSFs when chemotherapy and radiation therapy are being administered jointly Smith et al. 2006 . No pediatric data are available to make recom- mendations for these clinical scenarios. The 2002 pediatric guidelines by Lehrnbecher and Welte recommend against G-CSF usage with concomi- tant chemotherapy and radiation therapy while no mention is made of utilization with radiation therapy alone.15.2.2 Optimal Administration of Colony-Stimulating Factors
The optimal CSF formulation in pediatric oncol- ogy patients as well as the best dosing schedule, route of administration and timing of administra- tion must all be considered when administering CSFs.15.2.2.1 Comparison of Granulocyte Colony-Stimulating Factor
and Granulocyte-Macrophage Colony-Stimulating Factor GM-CSF is not FDA approved for treating chemotherapy- induced myelosuppression or febrile neutropenia. A meta-analysis of G-CSF and GM-CSF trials for this purpose in adult oncology patients reported a signifi cantly increased rate of fever in patients receiving GM-CSF, a lack of head to head trials between GM-CSF and G-CSF, and GM-CSF being inef- fective in reducing febrile neutropenia compared with placebo Dubois et al. 2004 . EORTC adult guidelines recommend fi lgrastim, pegfi lgrastim or lenograstim not FDA approved with equipo- tency; ESMO recommends either fi lgrastim or pegfi lgrastim; and ASCO gives consideration for fi lgrastim, pegfi lgrastim and GM-CSF while cau- tioning that there is no long-term data with peg- fi lgrastim and no signifi cant comparative studies between G-CSF and GM-CSF Smith et al. 2006 ; ESMO 2007 ; Aapro et al. 2011 . Pediatric data are lacking. Lydaki et al. 1995 randomized a small cohort of pediatric oncology patients to G-CSF or GM-CSF and found a signifi cant delay in neutrophil recovery in those treated with GM-CSF although this had no bearing on antibi- otic usage or mean hospital stay.15.2.2.2 Optimal Dosing Adult guidelines recommend dosing of 5 mcgkg
of fi lgrastim, 100 mcgkg of pegfi lgrastim max 6 mg and 250 mcgm 2 of sargramostim Smith et al. 2006 ; ESMO 2007 ; Aapro et al. 2011 . Few pediatric studies are available. Cairo et al. 2001 compared 5 and 10 mcgkg of G-CSF starting 24 h after intensive chemotherapy for 123 pediatric patients with relapsed or refractory solid tumors and found no signifi cant difference in time to ANC ≥1.0 × 10 9 L, incidence of infection, febrile days, incidence of hospitalization or overall sur- vival. A small pediatric study comparing 100 mcgm 2 vs. 250 mcgm 2 of GM-CSF showed that duration of neutropenia was signifi cantly shortened in the 250 mcgm 2 arm with a trend toward decreased duration of febrile neutropenia and no noted difference in side effects Kubota et al. 1995 .15.2.2.3 Route of Administration
Although package inserts for CSFs consider intravenous and subcutaneous administration to be equipotent, adult data have found that 2–4 times dosing is required to achieve equivalent effect when either G-CSF or GM-CSF is given intravenous as compared to subcutaneous Eguchi et al. 1990 ; Kaneko et al. 1991 ; Stute et al. 1995 ; Honkoop et al. 1996 . Adult guide- lines all suggest subcutaneous administration for CSFs Smith et al. 2006 ; ESMO 2007 ; Aapro et al. 2011 . No pediatric data are available and no mention of route of administration is made in pediatric guidelines Schaison et al. 1998 ; Lehrnbecher and Welte 2002 . In the pediatric clinical setting, intravenous G-CSF is often used when the patient is admitted while subcutaneous dosing is given when at home with no dose adjustment.15.2.2.4 Optimal Timing
Pediatric guidelines suggest initiation of CSFs 1–5 days after completion of chemotherapy whileParts
» 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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