G csf guideline


Published on

  • Be the first to comment

  • Be the first to like this

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

G csf guideline

  1. 1. What’s New in JCO2006 Update of ASCO Practice Guideline Recommendationsfor the Use of White Blood Cell Growth Factors:Guideline SummaryContext 4. Use of CSF to Increase Chemotherapy DoseASCO convened an Update Committee composed of the Intensity and Dose Densityoriginal Expert Panel and select ad hoc members to present Data on using CSF to increase dose-intensity or -densitythe 2006 evidence-based clinical practice guideline update chemotherapy regimens are limited. Evidence has shown that(J Clin Oncol 24:3187-3205, 2006) for the use of the use of CSF allows for a moderate increase in dose-densehematopoietic colony-stimulating factors (CSF). (but not dose-intense) regimens in certain settings (e.g., node- positive breast cancer; and possibly non-Hodgkin’sUpdated 2006 Recommendations lymphoma pending confirmation of results of individualSee Table 1 for a summary of the updated 2006 trials). This treatment approach should only be used withinrecommendations and specific considerations. Table A1 lists the constructs of a clinical trial or if supported bythe incidence of toxicities associated with selected appropriate evidence.chemotherapy regimens.1. Primary Prophylactic CSF Administration 5. Use of CSF As Adjuncts to Progenitor-(first and subsequent-cycle use) Cell TransplantationClinical trial data support the use of CSF when the risk of Major complications of high-dose chemotherapy supportedfebrile neutropenia (FN) is in the range of 20% or higher. by autologous bone marrow transplantation or peripheral-This recommendation represents a departure from the 2000 blood progenitor cell (PBPC) transplantation include diseaseupdate, which recommended the use of CSF when the risk of recurrence, infection, delayed or incomplete engraftment, andFN was 40% or higher. Most commonly used regimens have organ damage from the ablative regimen. The use of CSF toan FN risk of less than 20%. Oncologists should consider the mobilize PBPC and to shorten the period of neutropenia afteroptimal chemotherapy regimen, individual patient risk factors cytoreduction and PBPC transplantation is well established.and treatment intention when deciding whether to useprophylactic CSF. The use of regimens that do not require 6. Use of CSF in Patients With Acute Leukemia andCSF because of equal efficacy and lower risk of FN remainsstandard medical practice. Myelodysplastic Syndromes Considerations and available evidence vary for acute myeloid2. Secondary Prophylactic CSF Administration leukemia (AML), myelodysplastic syndrome (MDS), acuteSecondary prophylaxis with CSF is recommended for a select lymphocytic leukemia (ALL), and acute leukemia in relapse.group of patients. Oncologists should be mindful of previous Several studies have shown that CSF administration canneutropenic complications, prior CSF administration, and produce modest decreases in the duration of neutropeniaappropriateness of dose reduction. No definitive conclusions when begun shortly after completion of the initial inductioncan be drawn regarding the benefits of secondary prophylaxis chemotherapy for patients with AML. Studies on CSFon survival, quality of life, or cost. priming of leukemia cells in patients with AML produced results showing no effect on complete response rates or overall3. Therapeutic Use of CSF survival. Additional studies on AML patients (those inTherapeutic intervention with CSF can help reduce the remission) showed a seemingly profound shortened durationincidence of infectious episodes and infection-related of neutropenia after consolidation chemotherapy. Thesemorbidity and mortality. However, therapeutic CSF use studies produced no effect on complete response duration orshould be reserved for patients with fever and neutropenia overall patient survival. Though CSF use can increase theand those at high risk for infection-associated complications absolute neutrophil count in neutropenic patients with MDS,or poor clinical outcomes. This intervention should not be data supporting the routine, long-term, continuous use ofroutinely used in afebrile patients or FN patients receiving CSF for this population are lacking. Using CSF for patientsantibiotic therapy. Clinical prediction models have been with ALL (after initial chemotherapy induction ordeveloped to help prospectively identify patients with cancer postremission course) may shorten the duration ofwho are at higher risk of complications as a result of fever and neutropenia by 1 week. However, CSF use in patients withneutropenia; a risk model for mortality in hospitalized relapsed or refractory acute leukemia may provide only a fewpatients has also been reported recently (Table 2). days of shortened neutropenia. 196 JOURNAL OF ONCOLOGY PRACTICE • V O L . 2, I S S U E 4 Copyright © 2006 by American Society of Clinical Oncology. All rights reserved.
  2. 2. Table 1. Summary of 2006 Recommendations for the Use of CSF Setting/Indication Recommendation Primary prophylaxis Primary prophylaxis is recommended for the prevention of FN in patients who have a high risk of FN based on age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. For “dose-dense” regimens, CSF is required and recommended. Clinical trial data support the use of CSF when the risk of FN is in the range of 20% or higher. Primary prophylaxis: Special Certain clinical factors predispose to increased complications from prolonged neutropenia, including: patient age circumstances 65 years; poor performance status; previous episodes of FN; extensive prior treatment including large radiation ports; administration of combined chemoradiotherapy; bone marrow involvement by tumor-producing cytopenias; poor nutritional status; the presence of open wounds or active infections; more advanced cancer, as well as other serious comorbidities. In such situations, primary prophylaxis with CSF is often appropriate, even with regimens with FN rates of 20%. Secondary prophylaxis Secondary prophylaxis with CSF is recommended for patients who experienced a neutropenic complication from a prior cycle of chemotherapy (for which primary prophylaxis was not received), in which a reduced dose may compromise disease-free or overall survival or treatment outcome. In many clinical situations, dose reduction or delay may be a reasonable alternative. Therapeutic use: Afebrile CSF should not be routinely used for patients with neutropenia who are afebrile. neutropenia Therapeutic use: Febrile CSF should not be routinely used as adjunctive treatment with antibiotic therapy for patients with fever and neutropenia neutropenia. However, CSF should be considered in patients with fever and neutropenia who are at high-risk for infection-associated complications, or who have prognostic factors that are predictive of poor clinical outcomes. High-risk features include expected prolonged ( 10 days) and profound ( 0.1 109/L) neutropenia, age 65 years, uncontrolled primary disease, pneumonia, hypotension and multi-organ dysfunction (sepsis syndrome), invasive fungal infection, or being hospitalized at the time of the development of fever. Dose intensity/density of Dose-dense regimens should only be used within an appropriately designed clinical trial or if supported by chemotherapy convincing efficacy data. Adjuncts to progenitor-cell Administration of CSF to mobilize PBPC often in conjunction with chemotherapy, and their administration after transplantation autologous, but not allogeneic, PBPC transplantation is the current standard of care. AML: Initial or repeat CSF use following initial induction therapy is reasonable, though there has been no favorable impact on remission induction chemotherapy rate, remission duration, or survival. Patients 55 years of age may be most likely to benefit from CSF use. AML: CSF for priming Use of CSF for priming effects is not recommended. effects AML: Consolidation CSF use can be recommended after the completion of consolidation chemotherapy because of the potential to chemotherapy decrease the incidence of infection and eliminate the likelihood of hospitalization in some patients receiving intensive postremission chemotherapy. There seems to be more profound shortening of the duration of neutropenia after consolidation chemotherapy for patients with AML in remission than for patients receiving initial induction therapy. As yet there is no information about the effect of longer-acting pegylated CSFs in patients with myeloid leukemias, and they should not be used in such patients outside of clinical trials. MDS Intermittent administration of CSF may be considered in a subset of patients with severe neutropenia and recurrent infection. ALL CSF administration is recommended after the completion of the initial first few days of chemotherapy of the initial induction or first postremission course, thus shortening the duration of neutropenia of 1,000/mm3 by approximately 1 week. Acute leukemia in relapse CSF should be used judiciously, or not at all, in patients with refractory or relapsed myeloid leukemia since the expected benefit is only a few days of shortened neutropenia. Radiotherapy CSF should be avoided in patients receiving concomitant chemotherapy and radiation therapy, particularly chemotherapy involving the mediastinum. In the absence of chemotherapy, therapeutic use of CSF may be considered in patients receiving radiation therapy alone if prolonged delays secondary to neutropenia are expected. Older patients Prophylactic CSF for patients aged 65 years with lymphoma treated with curative chemotherapy (CHOP or more aggressive regimens) should be given to reduce the incidence of FN and infections. Pediatric patients As in adults, the use of G-CSF is reasonable for the primary prophylaxis of pediatric patients with a likelihood of FN. Similarly, the use of G-CSF for secondary prophylaxis or for therapy should be limited to high-risk patients. However, the potential risk for secondary myeloid leukemia or myelodysplastic syndrome associated with G-CSF represents a concern in children with ALL whose prognosis is otherwise excellent. For these reasons, the specific use of G-CSF in children with ALL should be considered carefully. Continued on next pageCopyright © 2006 by American Society of Clinical Oncology. J U L Y 2006 • www.jopasco.org 197All rights reserved.
  3. 3. Table 1. Summary of 2006 Recommendations for the Use of CSF (continued) Setting/Indication Recommendation Comparative clinical activity No guideline recommendation can be made regarding the equivalency of the two colony-stimulating agents. of G-CSF and GM-CSF Further trials are recommended to study the comparative clinical activity, toxicity, and cost-effectiveness of G- CSF and GM-CSF. Treatment for radiation Current recommendations for the management of patients exposed to lethal doses of total-body radiotherapy, injury but not doses high enough to lead to certain death due to injury to other organs, includes the prompt administration of CSF or pegylated G-CSF.Abbreviations: CSF, colony-stimulating factors; FN, febrile neutropenia; PBPC, peripheral-blood progenitor cell; AML, acute myeloid leukemia;MDS, myelodysplastic syndrome; ALL, acute lymphocytic leukemia; CHOP, cyclophosphamide, doxorubicin, vincristine, prednisone; G-CSF,filgrastim; GM-CSF, sargramostim; pegylated G-CSF, pegfilgrastim.7. Use of CSF in Patients Receiving Radiotherapy 9. Use of CSF in the Pediatric PopulationWith or Without Concurrent Chemotherapy The use of CSF in pediatric patients will almost always beThough concurrent chemotherapy with radiation therapy is guided by clinical protocols. Several multicenter randomizedimportant in certain treatment settings, oncologists should clinical trials have evaluated prophylactic CSF in children,avoid CSF administration for these patients. However, in the particularly those with acute leukemia. Based on this research,absence of chemotherapy, and if prolonged delays secondary oncologists should consider cautiously the use of CSF into neutropenia are expected, patients receiving radiation children with ALL. When determining whether CSFtherapy alone may benefit from the therapeutic use of CSF. administration would prophylactically or therapeutically benefit a pediatric patient, the oncologist should consider the patient’s likelihood of developing FN and incidence of other8. Use of CSF in Older Patients: New Topic risk factors.Aging is one of the conditions for which prophylactic use ofgrowth factors may be indicated irrespective of the thresholdrisk of neutropenia. However, aside from data available in 10. CSF Initiation, Duration, Dosing,patients with lymphoma, there is insufficient evidence to and Administrationsupport the use of prophylactic CSF in patients, based solely Filgrastim (G-CSF), pegfilgrastim (pegylated G-CSF), andon age. Oncologists should consider additional patient risk sargramostim (GM-CSF) are the growth factors currently infactors when deciding whether to administer CSF to use. The administration protocol for each agent varieselderly patients. according to setting (Table 3).Table 2. Clinical Prediction and Risk Models Clinical Prediction Model for Prospectively Risk Model for Mortality in Hospitalized Patients: Independent Risk Factors Identifying Cancer Patients at Higher Risk of for Inpatient Mortality in Hospitalized Patients With FN Complications due to Fever and Neutropenia: Reported Risk Factors for Serious Medical Complications in Patients With Established FN Development of FN as inpatient Comorbidities: CHF, PE, lung, renal, liver, and cerebrovascular disease Hypotension Infectious complications: hypotension, pneumonia, bacteremia, fungal infection Sepsis Cancer type (leukemia, lung cancer) Cardiovascular disease Age 65 years Pulmonary disease Leukemia or lymphoma diagnosis Age 65 years Prior fungal infection Visceral organ involvement Organ dysfunction Uncontrolled malignancy Severity and duration of neutropeniaAbbreviations: FN, febrile neutropenia; CHF, congestive heart failure; PE, pulmonary embolism. 198 JOURNAL OF ONCOLOGY PRACTICE • V O L . 2, I S S U E 4 Copyright © 2006 by American Society of Clinical Oncology. All rights reserved.
  4. 4. Table 3. Recommendations for CSF Initiation, Duration, Dosing, and Administration Growth Factor Setting Initiation Duration Dose G-CSF (filgrastim) Myelotoxic chemotherapy 24-72 hours after Continue until ANC at least Adults: 5 g/kg/d administration of 2-3 109/L subcutaneous chemotherapy High-dose therapy and 24-120 hours after Continue until ANC at least Adults: 5 g/kg/d autologous stem-cell administration of high- 2-3 109/L subcutaneous rescue dose therapy PBPC mobilization Start at least 4 days before Continue until last Adults: 10 g/kh/d first leukapheresis leukapheresis subcutaneous Pegylated G-CSF Myelotoxic chemotherapy 24 hours after completion Once in each 6 mg† (pegfilgrastim)* of chemotherapy chemotherapy cycle GM-CSF (sargramostim)‡ Bone marrow Day of bone marrow Continue until ANC 1.5 Adults: 250 g/m2/d for all transplantation or AML infusion and not less than 109/L for 3 consecutive clinical settings other than 24 hours from the last days§ PBPC mobilization chemotherapy and 12 hours from most recent radiotherapyNOTE. The long-term effects of long acting growth factors are unknown, and the Update Committee expressed concern about potentialleukocytosis, late neutropenia after discontinuation of pegylated G-CSF, and the need for long-term safety data.Abbreviations: G-CSF, filgrastim; ANC, absolute neutrophil count; PBPC, peripheral-blood progenitor cell; pegylated G-CSF, pegfilgrastim; GM-CSF, sargramostim.* Pegfilgrastim is not currently indicated for stem-cell mobilization. The safety and efficacy of pegylated G-CSF has not yet been established in thesetting of dose-dense chemotherapy.† The 6-mg formulation should not be used in infants, children, or small adolescents weighing 45 kg.‡ Because GM-CSF has been licensed specifically for use after autologous or allogeneic BMT and for AML, the manufacturer’s instructions foradministration are limited to those clinical settings.§ The drug should be discontinued early or the dose be reduced by 50% if the ANC increases to 20 109/L.11. Special Comments on Comparative Clinical based on improvements in survival, quality of life, toxicityActivity of G-CSF and GM-CSF reduction, and cost-effectiveness. The Committee agreedNo guideline recommendation can be made regarding the unanimously that reduction in FN was an important clinicalequivalency of the two colony-stimulating agents. As in 2000, outcome that justified use of CSF, regardless of impact onfurther trials are recommended to study the comparative other factors, when the risk of FN was about 20% and noclinical activity, toxicity, and cost-effectiveness of G-CSF other equally effective regimen that did not require CSFand GM-CSF. was available.12. Special Comments on Growth Factors As aTreatment for Radiation Injury: New Topic MethodologyCurrent recommendations for the management of patients The 2006 Update Committee performed a completeexposed to lethal doses of total-body radiotherapy, but not literature review and analysis of data published from 1999doses high enough to lead to certain death due to injury to through September 2005. Whenever possible, the Committeeother organs, includes the prompt administration of CSF or focused on randomized controlled trials and systematicpegylated G-CSF. reviews and meta-analyses of published trials.13. Impact of CSF on Quality of Life and HealthCare CostsGrowth factors should be used when indicated for clinical Additional Resourcesreasons, not economic ones. When available, alternative The 2006 Update is available in the July 1, 2006, printregimens offering equivalent efficacy but not requiring CSF edition of JCO and also at www.jco.org (J Clin Oncolsupport should be utilized. Further research into CSF cost 24:3187-3205, 2006). In addition to the full text of theimplications and impact on quality of life is warranted. guideline recommendations, available online at http:// www.asco.org/guidelines/wbcgf, further resources fromDiscussion ASCO include a patient guide and PowerPoint slide set.The 2006 Update Committee was guided by the 1996 ASCO A CSF flow sheet and orders form is available online atoutcomes criteria that justify the use of a drug or technology www.jopasco.org.Copyright © 2006 by American Society of Clinical Oncology. J U L Y 2006 • www.jopasco.org 199All rights reserved.
  5. 5. The ASCO 2006 Update of Recommendations for the Use of Jeffrey Crawford, Scott J. Cross, George Demetri,White Blood Cell Growth Factors was developed and written by Christopher E. Desch, Philip A. Pizzo, Charles A. Schiffer,Thomas J. Smith (Chair), James Khatcheressian, Gary H. Lee Schwartzberg, Mark R. Somerfield, George Somlo,Lyman, Howard Ozer, James O. Armitage, Lodovico James C. Wade, James L. Wade, Rodger J. Winn,Balducci, Charles L. Bennett, Scott B. Cantor, Antoinette J. Wozniak, and Antonio C. Wolff. It is important to realize that many management questions have not been comprehensively addressed in randomized trials and guidelines cannot always account for individual variation among patients. A guideline is not intended to supplant physician judgment with respect to particular patients or special clinical situations and cannot be considered inclusive of all proper methods of care or exclusive of other treatments reasonably directed at obtaining the same results. Accordingly, ASCO considers adherence to this guideline to be voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient’s individual circumstances. In addition, the guideline describes administration of therapies in clinical practice; it cannot be assumed to apply to interventions performed in the context of clinical trials, given that clinical studies are designed to test innovative and novel therapies in a disease and setting for which better therapy is needed. Because guideline development involves a review and synthesis of the latest literature, a practice guideline also serves to identify important questions for further research and those settings in which investigational therapy should be considered. Assess and Improve Care in Your Medical Oncology Practice The goal of ASCO’s Quality Oncology Practice Initiative (QOPI) is to promote excellence in cancer care by helping medical oncologists create a culture of self-examination and improvement. QOPI practices benefit from knowledge of practice strengths and weaknesses and access to tools and strategies to improve care. By participating in QOPI, physicians receive practice-specific data, aggregate data from their peers for comparison, and access to resources for implementing best practices. All practice-specific data are released only to that practice, and are kept strictly confidential. Join the oncologist-led initiative for assessing and improving care in medical oncology practice. Visit www.asco.org/QOPI. AMERICAN SOCIETY OF CLINICAL ONCOLOGY 200 JOURNAL OF ONCOLOGY PRACTICE • V O L . 2, I S S U E 4 Copyright © 2006 by American Society of Clinical Oncology. All rights reserved.
  6. 6. Table A1. Incidence of Hematologic and Infectious Toxicities Associated With Selected Chemotherapy Regimens No. of Grade 4 Grade 4 Grade ≥ 2 Grade ≥ 3 Cancer Stage and Prior Patien Leukopenia Neutropenia Febrile Fever Infection Infectious Histology Therapy Regimen ts (%)* (%) Neutropenia (%) (%)‡ (%)§ Death (%) Adult AML Newly diagnosed Ara-C/DNR 163 93 — — 37 (no 64 12 infection) AIDS-related Advanced/1st and 2nd Lipo Dox [+G(M)-CSF] 133 36 (3+4) 6 — 1 — 0 Kaposis sarcoma line VP–16 (oral) 36 — 19.4 — 8 — — Paclitaxel 56 — 35 — — — — AIDS-related† Intermediate- and high- CHOP (Modified) 40 — 25 (3+4) 2.5 — — 10 NHL grade, untreated CHOP + G-CSF 25 — 13 (3+4) 0 — — — Bladder Advanced, no prior GC 203 — 29.9 2 0 2.5 1 systemic therapy MVAC 202 — 65.2 14 3.1 15.1 2.5 Prior adjuvant allowed CBDCA/Pac ± G-CSF 33 — 21 21 — 1 patient sepsis 0 Breast Adjuvant CA (60 mg/m2) 1060 — 62 10 (hospitalized) — 17 0 CA→T (all dose levels) 1590 — 16 3 — 11 0 CEF 351 49.9 89.7 8.5 — — 0 TAC 109 — — 23.8 — — — Adjuvant (dose dense) A→T→C 484 1 24 3 — 3 0 A→T→C + G-CSF 493 — 3 2 — 4 0 AC→T 501 11 43 6 — 5 0 495 6 9 2 — 3 0 AC→T + G-CSF Metastatic (1st line) 165 — 77.8 12.3 — 4.3 1 death A (75) 161 — 78.6 5.7 — 2.5 1 death Doc (100) 215 — 88 (3+4) 10 — 2 0.5 AC 214 — 97 (3+4) 33 — 8 0 AT 54 — 100 (3+4) 34 — 2 0 TAC Metastatic (2nd line) 255 — 11 16 — — <1 Cap Doc 256 — 12 21 — — 0 Doc Colorectal Adjuvant 5-FU/LV/L 449 2 — — — — <1 5-FU/LV 116 15 (high LV) — — — — 1.7 22 (low LV) Advanced IFL 189 — 24 7.1 — 1.8 <1 FL 226 — 42.5 14.6 — 0 1.4 I 226 — 12.1 5.8 — 2.2 <1 FOLFOX4 152 — 17 6 — — 0 FOLFIRI 145 20.4 (3+4) 28.8 (3+4) 9.3 — 1.9 <1 Advanced (one prior CPT-11 (350 mg/m2 Q3 213 36 (3+4) 48 (3+4) 14 — <1 3 deaths chemo allowed) wk) Gastric Advanced ECF (infusion) 289 13 32 — 1 6 <1 Germ cell Advanced BEP 141 — 34 (all heme 60 — — — 2 VIP 145 — toxicities) — — — 2.8 Relapsed VeIP 135 — — 71 — — 2.1 (all deaths) Head/neck Recurrent; metastatic FU/CBDCA 86 2.3 1.2 — — — 1.2 CBDCA/Pac 41 4.9 9.8 — — — 2.4 Cis/Doc 36 — 71 6 — 11 0 Induction Cis/Doc/FU 43 — 95 (3+4) 19 — 2 0 Lung Extensive SCLC Cis/VP-16 159 14 38 — — 8 ≤ 6 (all toxic No prior treatment CAV 156 28 52 — — 16 deaths) CBDCA/VP-16 74 5 — — — — ≤ 4 (all toxic Cis/CPT-11 77 4 25.3 — 1.3 5.3 deaths) 0 Recurrent Topo 107 31.7 70.2 28 — 4.7 2.6 CAV 104 43.6 71.7 26 — 4.8 3.7 Advanced NSCLC Cis/VNR 206 — 59 10 — — 2.9 No Prior Treatment Cis/Pac (24 hr) 288 — 57 16 — 10 Cis/Gem 288 — 39 4 — 7 1 Cis/Doc 289 — 48 11 — 9 2 CBDCA/Pac 290 — 43 4 — 6 1 CBDCA/Doc 406 49.5 (3+4) 74.4 (3+4) 3.7 — 11 2 1 Recurrent (2nd line) Doc (75 mg/m2) 276 40.2 (3+4) — 12.7 — 3.3 — Pemetrexed 265 5.3 (3+4) — 1.9 — 0 — — Lymphoma Relapsed HD; prior MOPP 123 — 22 — 3 (no infection) 13 1 RT only ABVD 115 — 3 — 5 (no infection) 2 0 Intermediate- and high- CHOP 216 25 22 — — 5 (≥ grade 4) 1 grade CHOP-R 33 1.2 58 18 6 6 0 NHL; no prior treatment VAPEC-B 39 — 72 44 — 5 patient 2 deaths Relapse NHL ESHAP 122 — 500/_L median 30 — — 4.1 DHAP 90 — 53 48 — 31 11 Multiple myeloma Untreated VAD ± Inf 169 — — — — — 1.2 Recurrent/refractory VAD ± Inf 52 65.4 — — — 32.7 7.7 Ovary Resected, minimal Cis/Pac (24 hours) 400 12 78 Few instances — — — residual CBDCA/Pac 392 6 72 — — — — Salvage Topo 139 30.1 82.4 18 — — 0 Sarcoma Advanced, untreated AD 186 32 38 — — — 0 MAID 188 86 79 — — — 3.5 A 263 13 — — 5.3 (all study 11 (all study arms) — AI 258 32 — — arms) — — CYVADIC 142 15 — — — — Special populations NHL, untreated CHOP 197 — — — 5 (3+4) 20 16 patients (elderly) CHOP-R 202 — — — 2 12 (both arms) Breast, adjuvant CMF 76 4 (grade 3) — — — — 0 9 9 * Grade 4 leukopenia: WBC count < 1.0 × 10 /L; grade 4 neutropenia: ANC < 0.5 × 10 /L. † Most patients received antiretroviral therapy and data do not include opportunistic infections. ‡ Common toxicity criteria fever ≥ grade 2; ≥ 38.1°C (≥ 100.5°F). § Infection ≥ grade 3: systemic infection requiring hospitalization.Copyright © 2006 by American Society of Clinical Oncology. J U L Y 2006 • www.jopasco.org 201All rights reserved.