hematology and oncology
Management of Adverse Effects of Cancer Therapy
Cytopenias
Decreased blood concentrations of red blood cells (RBCs), white blood cells (WBC), especially granulocytes, and platelets result from diverse systemic cancer therapies, especially conventional chemotherapy drugs, and radiation therapy. Decreased levels of RBCs are common in patients with cancer. Decreases in RBCs result from a direct effect of the cancer (especially in blood and bone marrow cancers such as leukemias, lymphomas, and multiple myeloma) and from effects of cancer therapy, especially conventional cancer (chemotherapy) drugs. Often anemia requires no therapy. Some patients, especially those with comorbidities such as arteriosclerotic cardiovascular disease, may benefit from RBC transfusions. Others may benefit from receiving recombinant erythropoietin, which can substitute for RBC transfusions. Some data suggest erythropoietin use can have adverse effects on cancer prognosis and is prothrombotic. Guidelines on RBC transfusion and erythropoietin use are available, but recommendations are controversial ( Cytopenia references ). Decreased platelet concentration is common in patients with cancer. Decreases in platelets result from a direct effect of the cancer (especially blood and bone marrow cancers such as leukemias, lymphomas, and multiple myeloma) and from effects of cancer therapy, especially conventional chemotherapy drugs. The risk of bleeding is inversely proportional to the platelet count (see table). Platelet concentrations<10,000/microL (10 × 109/L) are dangerous and require platelet transfusions. Molecularly cloned hormones, such aseltrombopagandavatrombopag, which stimulate megakaryocytes to produce platelets, have been used. Leukocyte depletion of transfused blood products may prevent alloimmunization to platelets and should be used in patients expected to need platelet transfusions during multiple courses of chemotherapy or for candidates for hematopoietic cell transplants. Leukocyte depletion also lowers the probability of acquiring a Cytomegalovirus (CMV) Infection . /L) in people with African ancestry (see also Neutropenia ). Decreases in granulocytes result from a direct effect of the cancer (especially blood and bone marrow cancers such as leukemias, lymphomas, and multiple myeloma) and from effects of cancer therapy, especially conventional chemotherapy drugs. The risk of infection is inversely proportional to the granulocyte count. A granulocyte concentration Afebrile patientswith neutropenia require close outpatient follow-up for detection of fever and should be instructed to avoid contact with sick people or areas frequented by large numbers of people (eg, shopping malls, airports). Although most patients do not require antibiotics, patients with severe immunosuppression are sometimes giventrimethoprim/sulfamethoxazole (one double-strength tablet/day) as prophylaxis forPneumocystis jirovecii. In transplant patients or others receiving high-dose chemotherapy, antiviral prophylaxis (acyclovir800 mg orally twice a day or 400 mg IV every 12 hours) should be considered if serologic tests are positive for herpes simplex virus. Fever>38.5°C on two or more occasions in a patient with neutropenia is a medical emergency. An extensive evaluation for potential infection sources should be made and blood cultures done. Typically, systemic broad-spectrum antibiotics are given before culture results are known and therapy modified as needed. Patients with persistent fever unresponsive to antibiotics are often started on systemic antifungal and sometimes antiviral drugs. Evaluation should include immediate chest x-ray and cultures of blood, sputum, urine, stool, and any suspect skin lesions. Examination includes possible abscess sites (eg, skin, ears, sinuses, perirectal area), skin and mucosa for presence of herpetic lesions, retina for vascular lesions suggestive of infectious emboli, and catheter sites. Rectal examination and use of a rectal thermometer should be avoided. Other evaluation should be guided by clinical findings. Febrile neutropenic patients should receive broad-spectrum antibiotics chosen on the basis of the most likely organism. Typical regimens includecefepimeorceftazidime2 g IV every 8 hours immediately after samples for culture are obtained. If diffuse pulmonary infiltrates are present, sputum should be tested forP. jirovecii, and if positive, appropriate therapy should be started. If fever resolves within 72 hours after starting empiric antibiotics, they are continued until the neutrophil count is>500/microL (0.5 × 109/L). If fever continues, antifungal drugs should be added. Reassessment for infection, often including CT of the chest and abdomen, is also done. . Guidelines for appropriate use of these drugs are available ( Cytopenia references ). In selected patients with neutropenia related to chemotherapy, especially after high-dose chemotherapy, granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) may be started to shorten the duration of neutropenia. G-CSF 5 mcg/kg subcutaneously once/day up to 14 days and longer-acting forms (eg, Many centers use outpatient treatment with G-CSF in selected low-risk patients with fever and neutropenia. Candidates must not have hypotension, altered mental status, respiratory distress, uncontrolled pain, or serious comorbid illnesses, such as diabetes, heart disease, or hypercalcemia. The regimen in such cases requires daily follow-up and often involves visiting nurse services and home antibiotic infusion. Some regimens involve oral antibiotics, such asciprofloxacin750 mg twice a day plusamoxicillin/clavulanate 875 mg twice a day or 500 mg 3 times a day. If no defined institutional program for follow-up and treatment of neutropenic fever is available in an outpatient setting, then hospitalization is required. 1.Bohlius J, Bohlke K, Castelli R, et al: Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH Clinical Practice Guideline Update.J Clin Oncol37(15):1336–1351, 2019. doi: 10.1200/JCO.18.02142 2.Crawford J, Becker PS, Armitage JO, et al: Myeloid Growth Factors, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology.J Natl Compr Canc Netw15, 12; 10.6004/jnccn.2017.0175 3.Smith TJ, Bohlke K, Lyman GH, et al: Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update.J Clin Oncol33(28):3199–3212, 2015. doi: 10.1200/JCO.2015.62.3488 