hematology and oncology
Neutropenia
Treatment of Neutropenia
Treatment of associated conditions (eg, infections, stomatitis) Sometimes antibiotic prophylaxis Myeloid growth factors Discontinuation of suspected etiologic agent (eg, drug) Sometimes corticosteroids Suspected infections are always treated immediately. If fever or hypotension is present, serious infection is assumed, and empiric, high-dose, broad-spectrum antibiotics are given IV. Regimen selection is based on the most likely infecting organisms, the antimicrobial susceptibility of pathogens at that particular institution, and the regimen’s potential toxicity. Because of the risk of creating resistant organisms,vancomycinis used only if gram-positive organisms resistant to other drugs are suspected. Indwelling vascular catheters can usually remain in place even if bacteremia is suspected or documented, but removal is considered if infections involveS. aureus,Bacillus,Corynebacterium, orCandidaor another fungus or if blood cultures are persistently positive despite appropriate antibiotics. Infections caused by coagulase-negative staphylococci generally resolve with antimicrobial therapy alone. Indwelling Foley catheters can also predispose to infections in neutropenic patients, and change or removal of the catheter should be considered for persistent urinary infections. If cultures are positive, antibiotic therapy is adjusted to the results of sensitivity tests. If a patient defervesces within 72 hours, antibiotics are continued for at least 7 days and until the patient has no symptoms or signs of infection. When neutropenia is transient (such as that following myelosuppressive chemotherapy), antibiotic therapy is usually continued until the neutrophil count is>500/mcL (> 0.5 × 109/L); however, if cultures remain negative, stopping antimicrobials can be considered in selected patients with persistent neutropenia, especially those in whom symptoms and signs of inflammation have resolved. Fever that persists>72 hours despite antibiotic therapy suggests A nonbacterial cause Infection with a resistant species Superinfection with a 2nd bacterial species Inadequate serum or tissue levels of the antibiotics Localized infection, such as an abscess Neutropenic patients with persistent fever are reassessed every 2 to 4 days with physical examination, cultures, and a chest x-ray. If the patient is well except for the presence of fever, the initial antibiotic regimen can be continued, and drug-induced fever should be considered. If the patient is deteriorating, alteration of the antimicrobial regimen is considered ( Treatment references ). Overview of Fungal Infections are the most likely cause of persistent fevers and deterioration. Antifungal therapy is added empirically if unexplained fever persists after 3 to 4 days of broad-spectrum antibiotic therapy. Selection of the specific antifungal drug (eg, If fever persists after 3 weeks of empiric therapy (including 2 weeks of antifungal therapy) and the neutropenia has resolved, then stopping all antimicrobials can be considered and the cause of fever reevaluated. /L). Also, antifungal therapy can be given for afebrile patients with neutropenia who are at higher risk of fungal infection (eg, after Hematopoietic Stem Cell Transplantation or intensive chemotherapy for 75), growth factors are indicated ( Treatment references ). In general, most clinical benefit occurs when the growth factor is administered beginning about 24 hours after completion of chemotherapy. Patients with neutropenia caused by an idiosyncratic drug reaction may also benefit from G-CSF, particularly if a delayed recovery is anticipated. The usual dose for G-CSF ( Glucocorticoids, anabolic steroids, and vitamins do not stimulate neutrophil production and are generally not helpful to patients with neutropenia. If acute neutropenia is suspected to be caused by a drug or a toxin, all potential etiologic agents are stopped. If neutropenia develops during treatment with an antibiotic known to induce low counts (eg,chloramphenicol), then switching to an alternative antibiotic is recommended. Saline orhydrogen peroxidegargles every few hours, liquid oral rinses (containing viscouslidocaine,diphenhydramine, and liquid antacid), anesthetic lozenges (benzocaine15 mg every 3 or 4 hours), orchlorhexidinemouth rinses (1% solution) twice a day or 3 times a day may relieve the discomfort of stomatitis with oropharyngeal ulcerations. Oral or esophageal candidiasis is treated withnystatin(400,000 to 600,000 units oral rinse 4 times a day; swallowed if esophagitis is present),clotrimazoletroche (10 mg slowly dissolved in the mouth 5 times a day), or systemic antifungal drugs (eg,fluconazole). A semisolid or liquid diet may be necessary during acute stomatitis or esophagitis, and topical analgesics (eg,viscouslidocaine) may be needed to minimize discomfort. Neutrophil production and deployment in Neutropenia caused by intrinsic defects in myeloid cells or their precursors , Long-term G-CSF has also been used in other patients with mild chronic neutropenia (including those with myelodysplasia, HIV infection, autoimmune disorders). Clinical benefits of treatment with G-CSF are less clear, especially for patients who do not have severe neutropenia. For patients with autoimmune disorders such as some patients who have the LGL syndrome or who have had an organ transplant,cyclosporinecan also be beneficial. In the past, splenectomy was used to increase the neutrophil count in patients with splenomegaly and splenic sequestration of neutrophils (eg, Felty syndrome); however, because growth factors and other newer therapies are often effective, splenectomy should be avoided. Splenectomy can be considered for patients with persistent painful splenomegaly or with severe neutropenia (ie,<500/mcL [< 0.5 × 109/L]) and serious problems with infections in whom other treatments have failed. Patients should be vaccinated against infections caused byStreptococcus pneumoniae,Neisseria meningitidis, andHaemophilus influenzaebefore splenectomy because splenectomy predisposes patients to infection by encapsulated organisms. 1.Pizzo PA: Management of patients with fever and neutropenia through the arc of time: A narrative review.Ann Intern Med170(6):389-397, 2019. doi: 10.7326/M18-3192 2.Becker PS, Griffiths EA, Alwan LM, et al: NCCN guidelines insights: Hematopoietic growth factors, version 1.2020.J Natl Compr Canc Netw18(1):12-22, 2020. doi: 10.6004/jnccn.2020.0002 3.Dale DC, Bolyard AA, Shannon JA, et al: Outcomes for patients with severe chronic neutropenia treated with granulocyte colony-stimulating factor.Blood Adv6(13):3861-3869, 2022. doi: 10.1182/bloodadvances.2021005684 