Neutropenia and Febrile Neutropenia in Cancer Patients

I Neutropenia and Febrile Neutropenia in Cancer Patients DR. LE IVA Neutropenia vs. Febrile Neutropenia – Drugs + Bugs Neutropenia i Absolute neutrophil count (ANC) of <500 neutrophils/mcL Eton Febrile Neutropenia (FN) dWo Absolute neutrophil count (ANC) of <500 y neutrophils/mcL OR an anticipated decline to ≤500 within the next 48 hours, accompanied by a SINGLE oral temperature of ≥38.3°C OR a temperature ≥38.0°C for a duration of over 1 hour Etiology of Cancer Related Neutropenia • Some Chemotherapy agents are myelotoxic – especially in combination • XRT is myelotoxic and can cause deep and compounded neutropenia • DNA damaging agents may cause prolonged bone marrow suppression • Cancer (solid or liquid tumors) – may infiltrate bone marrow and cause decreased production or increased destruction of immune cells pointof Nadir salowest WBC Onset and Duration of Neutropenia • Agent Dependent • Neutrophil counts often start to drop ~week after each round of chemotherapy begins • Bendamustine and carboplatin often occur later (~14-21 days) • Neutrophil levels reach nadir ~7 - 14 days after treatment • Most likely to develop an infection during nadir • Monocytes rise before neutrophils and WBCs increase • Elevated monocytes = patient is going to recover from the neutropenia within a few days • Takes time for bone marrow to restart normal production of neutrophils and have them migrate out to the periphery - may take 3 - 4 weeks to reach a normal level again • Cycle days determined based on average nadir – dose dense regimens REQUIRE growth support to prevent nadir from occurring and allow a person to stay on “schedule” for maximal cancer cell cure (mostly for curative stages) Clinical Presentation of Neutropenia and FN Neutropenia • Fatigue • ANC <500 • Thrush, oral/esophageal/vaginal candidiasis Febrile Neutropenia • • • • • • Fatigue ANC <500 Febrile: >100.5 ᴼ Chills SIRS (in this case the patient may NOT be febrile due to sepsis but infection is present) Other symptoms depend on the bug(s) causing infection(s) – respiratory, sore throat, diarrhea, discharge, pain on urination, redness/swelling around port, etc o Myeloid Growth Factors – Granulocyte Stimulating Factors (G-CSFs) prophylectis • Granulocyte colony stimulating factors (G-CSF) – Filgrastim and Pegfilgrastim and biosimilars • Indication: • Decrease the incidence of infection in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever 8 Granulocyte-macrophage colony stimulating factors (GM-CSF)to treatnutropenia • Sargramostim (Leukine) • Mechanism of Action: • GM-CSF - group of growth factors termed colony stimulating factors which support survival, clonal expansion, and differentiation of hematopoietic progenitor cells. Guy • GM-CSF induces partially committed progenitor cells to divide and differentiate in the granulocyte-macrophage pathways which include neutrophils, monocytes/macrophages and myeloid-derived dendritic cells. • Indication: • Used for a variety of indications – mostly to do with bone marrow transplants and acute radiation induced hemopoietic toxicity. • For our purposes, used sometimes when patients are severely neutropenic with a high risk of infection related complication and who did not receive prophylactic G-CSFs. sake Drugs Used For Prophylaxis of FN Filgrastim (Neupogen®) Tbo-Filgrastim (Granix®) Filgrastim-aafi (Nivestym®) Filgrastim-sndz (Zarxio®) Pegfilgrastim (Neulasta®, Onpro®) Pegfilgrastim-bmez (Ziextenzo®) Pegfilgrastim-cbqv (Udenyca®) Pegfilgrastim-jmdb (Fulphila®) Mechanism for Bone Pain Histamine Blockers Histamine meditor Filgrastim (Neupogen®) and Sisters Effector Cells • Neutrophils MOA: Stimulates the maturation and differentiation of neutrophil precursors Usual Dosage • 5 mcg/kg/day SQ or IV (usually round to either 300 or 480 mcg) ADRs • Bone Pain (~25%) • Acute Respiratory Distress Syndrome (ARDS) • *rarely can 3 cause splenic rupture Clinical Pearls • Begin no LESS than 24 hours AFTER chemotherapy • Can start up to 72 hours after chemo • Dosed daily (~5-7 days) • Start taking Claritin or Zyrtec day before for 2-3 days after beginning G-CSF O Dose it onceafter an arenaIt 2 Pegfilgrastim (Neulasta®, Onpro®) and Sisters Effector Cells Effector Cells • Neutrophils Usual Dosage Usual Dosage • 6 mg SQ once/on body injector available as well ADRs ADRs • Bone Pain (~25%) • Acute Respiratory Distress Syndrome (ARDS) • MOA: Stimulates the maturation and differentiation of neutrophil precursors Clinical Pearls Clinical Pearls **rarely can cause splenic rupture Ht • • • • • Begin no LESS than 24 hours AFTER chemotherapy** Can start up to 72 hours after chemo Dosed no less than EVERY 14 DAYS. Pegylated so kinetics can be hard to predict, some patients are not responsive. Start taking Claritin or Zyrtec day before for 2-3 days after beginning G-CSF Gmt Onpro® - Once activated, deploys 27 hours later https://www.neulasta.com/onpro/ Patient Education For Prevention of Febrile Neutropenia Nolneed Examples of Disease Settings and High-Risk Chemotherapy Regimens (>20% Incidence of FNP)  Breast Cancer memorise  Dose Dense-AC (doxorubicin, cyclophosphamide) followed by DDPaclitaxel  TAC (docetaxel, doxorubicin, cyclophosphamide)  TC (docetaxel, cyclophosphamide)  TCH (docetaxel, carboplatin, trastuzumab)  Colorectal Cancer  FOLFOXIRI (5FU, Leucovorin, oxaliplatin, irinotecan)  Non-Hodgkin Lymphoma  Dose adjusted EPOCH/R-EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin w/wout Rituximab)  ICE (Ifosfamide, carboplatin, etoposide)  HyperCVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)  Ovarian Cancer  Topotecan  Docetaxel  Small Cell Lung Cancer  Topotecan Evaluation of 2nd and Subsequent Cycles Sargramostim (Leukine®) Drug Used to Treat Neutropenia MOA: Stimulates maturation of Neutrophil, eosinophil, macrophages Dosing: 250 mcg/m2/day ADRs: First dose effect - (hypotension, flushing) Low grade fever, Bone pain, Injection site skin reaction Management of Neutropenia Management of Febrile Neutropenia • Infectious etiology is only identified in 40% to 50% of neutropenic fevers, with 10% - 30% having bacteremia • Common source of bacteremia enteric bacteria • Catheter-related bloodstream infections also important cause of infection in patients with febrile neutropenia • E.Coli, Klebsiella, Enterobacter, Pseudomonas, Coag negative Staph, and Group B Strep • At least two sets of blood cultures obtained • 1 peripheral venipuncture • 1 from central venous catheter, if present Fyd Assessing Risk – Determining Severity Outpatient vs. Inpatient Wrap Up Common problem • 10% of patients receiving treatment are hospitalized with FNP/infections; many more experience Neutropenia Etiology of Neutropenia and FN in cancer patients • Decreased production of WBCs • Increased destruction WBCs Defining Neutropenia and FN • ANC <500 – Neutropenia • Absolute neutrophil count (ANC) of <500 neutrophils/mcL OR an anticipated decline to ≤500 within the next 48 hours, accompanied by a SINGLE oral temperature of ≥38.3°C OR a temperature ≥38.0°C for a duration of over 1 hour – Febrile Neutropenia Evaluation of neutropenia and FN risk in cancer patients • CBC w/diff and Temperature, Regimen, disease (Heme/Solid Tumor), and KPS Prevention and Treatment Considerations and Risks • Appropriate initiation of G-CSF drugs • Limited use of Leukine; focus on treating infection source and prevention for future cycles • Treating FN based on risk assessment – Can we treat outpatient or inpatient?