Infections are common in patients with hematologic malignancies and can lead to significant morbidity and mortality. Risk for infection is directly linked to the neutropenia induced by intensive chemotherapeutic regimens. Additional risk factors include the use of indwelling devices, Ommaya reservoirs, urinary catheters, and disruption of mucosal barriers because of radiation- or chemotherapy-induced mucositis.
A review article published in Infectious Disease Clinics of North America discussed management strategies for infection as well as suggested prophylactic agents for various therapeutic regimens.
Coauthor Fiona He, MD, assistant professor of medicine in the division of hematology, oncology and transplantation at the University of Minnesota in Minneapolis, noted that she generally follows disease-specific guidelines for prophylaxis from the National Comprehensive Cancer Network (NCCN) and the Infectious Diseases Society of America (IDSA) because many new agents do not yet have established prophylactic protocols.
“The exceptions are those [agents] that have demonstrated higher than average risk for particular infections, such as idelalisib [which is associated with high risk for] pneumocystis pneumonia,” she said. “As a clinician who frequently uses novel drugs and immunotherapies that have only been on the market for a few years or less, [I believe] it is also very important to be aware of case reports of unexpected infections, which may be the first signal of infectious risk.”
Dr He also emphasized the importance of reporting unexpected infectious adverse events to the US Food and Drug Administration and the drug’s manufacturer, “as we try to effectively use new therapies that have not been tested on thousands of patients in trials due to the rarity of the disease or the push to get drugs on market for deadly cancers with few options.”
Infectious Risk of Individual Malignancies
The patient groups at highest risk of developing an infection are those with acute leukemias who are undergoing induction or consolidation therapy. Patients with acute myeloid leukemia (AML) frequently present with baseline neutropenia associated with hematopoietic stem cell dysfunction and marrow infiltration by leukemic blasts. The median time for neutrophil recovery to greater than 500 cells/mm3 after standard induction therapy with anthracycline and antimetabolites is 26 days in AML, and the risk of developing neutropenic fever during treatment is approximately 85% to 95%.
Fit patients with acute lymphoblastic leukemia (ALL) typically receive intensive multiagent chemotherapy for induction and intensification; the regimen includes high-dose steroids, anthracycline, vincristine, and peg-asparaginase followed by consolidation. Risk for infection is highest during induction therapy as neutropenia tends to occur less frequently during consolidation. One study in pediatric patients with ALL found that mortality related to infection accounted for 30% of deaths, with 68% of patient mortality secondary to bacteremia and 20% due to fungal infection.