Milone, G., Leotta, S., Cupri, A., Fauci, A. L., Spina, P., Parisi, M., . . . Tripepi, G. (2014). Palifermin reduces infection rate and hyperfibrinogenemia in patients treated with high-dose chemotherapy based on beam or BU-thiothepa. Bone Marrow Transplantation, 49, 1193–1197. 

To assess the effect of palifermin on mucositis and infection risk according to conditioning regimen used, and to evaluate the effect of palifermin on fibrinogen levels

This is a retrospective study of patients who underwent high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-SCT) because of hematologic malignancies. The authors evaluated the differences between a cohort of patients who received prophylaxis with palifermin and a matched control group of patients who did not receive this agent, and assessed the effect of palifermin on infection risk according to the conditioning regimen used, comparing BEAM, BU-CY, THIO-CY, and HD-PAM conditioning regimens.

• N = 120 (40 with palifermen, 80 in control)  
• MEDIAN AGE = 47 years in palifermin group and 50 years in control group
• MALES: 65% in palifermin group, 55% in control; FEMALES: 35% in palifermin group, 45% in control group
• KEY DISEASE CHARACTERISTICS: Diagnosis of MM in 57.5% of both groups; lymphoma diagnosis in 22.5% of palifermin group and 31.2% of control group; other diagnoses in 20% of palifermin group and 11.3% in control group
• OTHER KEY SAMPLE CHARACTERISTICS: Pretreatment with less than two lines of therapy prior to SCT in 19% of palifermin group and 29% of control group; HD-PAM in 65% of palifermin group and 57.5% in control group; BEAM/BUS in 35% of palifermin group and 42.5% of control group

• SITE: Single site    
• SETTING TYPE: Inpatient  
• LOCATION: Italian transplantation center

• PHASE OF CARE: Active antitumor treatment

Total of 120 patients who underwent SCT from 2000–2009 who either received palifermin prophylaxis or did not receive palifermin (control group)

Weekly blood cultures, serum galactomannan assay, and skin and oral culture swabs were used in afebrile patients. Standard febrile workup was used including blood and urine cultures, chest radiography (CXR), and a CT of the thorax within 72 hours of the onset of fever. Any infection arising during the first 30 days was evaluated. Fever of unknown origin (FUO), pneumonia, febrile gram-positive bacteremia, and CVC-related infections were all evaluated. Mucositis was assessed for all patients using daily inspection and grading according to daily mucositis scoring using Eastern Cooperative Oncology Group (ECOG) Common Terminology Criteria for Adverse Events (CTCAE) criteria. Gastrointestinal (GI) toxicity was deemed as severe if there were five or more stools per day.

Palifermin reduced rates of severe mucositis when evaluation was conducted taking into account conditioning type. There was a significant reduction in the severe mucositis rate in the BEAM/BUS group, whereas there was no significant reduction in the HD-PAM group. Palifermin had no effect on GI toxicity. FUO was significantly reduced in palifermin treated group. A reduction in severe infections (p = 0.06) existed in the BEAM/BUS group. A highly significant reduction in gram-positive infections existed in the BEAM/BUS group but not in HD-PAM group. Rate of patients with fevers was decreased in the palifermin group, but not significantly. A reduction in serum fibrinogen peak levels during the aplastic phase was observed with palifermin in the BEAM/BUS group but not in HD-PAM group.

Palifermin reduced FUO and severe infections unrelated to gram-positive bacteria with a more evident effect after conditioning based on BEAM/BUS. Severe mucositis was also reduced in the BEAM/BUS group but not in the HD-PAM group. The reduction in fibrinogen level substantiates the beneficial effect and may suggest a reduction in risk of mortality.

• Risk of bias (no blinding)
• Retrospective study

Nurses should monitor fever, mucositis, and onset of infection; educate patients on infection prevention and use of medications; and advocate for use of palifermin in high-risk populations, including the elderly, those receiving BEAM/BUS therapy, or heavily pretreated patients.