Antibacterial Prophylaxis Reduces the Incidence of Neutropenic Fever and the Rate of Infections in Patients with Multiple Myeloma Who Undergo An Autologous Stem Cell Transplantation.

Abstract 3334

Poster Board III-222

High dose melphalan (HDM) with autologous stem cell transplantation (ASCT) is the standard of care for eligible patients with multiple myeloma (MM) aged up to 65 years. This procedure is accompanied by a high incidence of neutropenic fever and infections that represent a leading cause of morbidity in these patients. The aim of this study was to evaluate the impact of prophylactic antibiotic administration after ASCT on the rate of infections and neutropenic fever. As of June 2009, 126 MM patients who underwent ASCT in our institution were randomized to receive or not prophylactic antibiotics post-ASCT. The prophylactic antibiotic regimen included IV vancomycin at a dose of 1000 mg once daily and ciprofloxacin at a dose of 500 mg, PO, twice daily. The administration of prophylactic antibiotics was started on day 0 of ASCT and continued until resolution of neutropenia or until the occurrence of a febrile event. In addition, all patients, irrespective of randomization, received fluconazole 200 mg, PO, once daily, and valacyclovir 500 mg, PO, once daily. G-CSF was given to all patients until resolution of neutropenia. When temperature exceeded 38°C for more than 1 hour, peripheral blood and urine samples were collected for microbiologic cultures, a chest X-ray was performed and empirical antibiotic treatment with IV wide spectrum antibiotics including amikacin, ceftazidime and therapeutic dose of vancomycin was started. This empirical therapy was later modified individually, according to cultures and sensitivity data. If patient remained febrile for 3-5 days after this initial treatment, a second-line regimen consisting of a carbapenem with a glycopeptide in the majority of cases was administered, until fever resolution. In the case of a proven or suspected fungal or viral infection, appropriate antifungal or antiviral therapy was administered. Sixty-nine (54%) patients were randomized to receive antibiotic prophylaxis. These patients had a significantly lower incidence of neutropenic fever post-ASCT compared to those who received only supportive care (58% versus 92%; p<0.0001). Prophylactic antibiotics were also associated with a lower probability of isolating a pathogen from blood or urine cultures (14.6% versus 34.6%, p=0.029; and 12.5% versus 30.8%, p=0.038, respectively). The administration of prophylactic antibiotics did not have a significant influence on patients' response to first line antibiotics after the development of neutropenic fever (72.5% versus 84.6%, p=0.155). Patients on prophylactic antibiotics developed neutropenic fever later after ASCT (mean days post-ASCT for febrile episode appearance: 6.3 versus 5.6; p=0.022). The prophylactic administration of antibiotics had no impact on patients' hospitalization period post-ASCT (p=0.746). To evaluate the influence of the number of stem cells re-infused on hematopoietic recovery on the development of a febrile neutropenic episode, we used a cut-off value of 10×10⁶ CD34+ cells/kg. Patients who received more than 10×10⁶ CD34+ cells/kg had a more rapid hematopoietic recovery (mean post-ASCT day with neutrophil count >0.5×10⁹/L: 9.6 versus 10.7, p<0.0001; and mean post-ASCT day with platelet count >25×10⁹/L: 9.7 versus 11.8, p<0.0001) and needed fewer days of hospitalization (mean hospitalization days: 19.3 versus 20.5, p=0.011) compared to all others. The interval with grade 4 neutropenia during hematopoietic recovery was reversely associated with the number of re-infused stem cells. However, patients who received more than 10×10⁶ CD34/kg appeared to have a similar incidence of fever or neutropenic fever as compared to patients with fewer CD34 cells/kg (p=0.756 and 0.506, respectively). Furthermore, neither the administration of prophylactic antibiotics nor the appearance of neutropenic fever correlated with patients' survival (p=0.654 and 0.193, respectively). The results of this prospective randomized trial demonstrate that patients with MM who received prophylactic antibiotics after ASCT had a lower incidence of neutropenic fever and infections. This advantage did not translate into a shorter hospitalization period or a better outcome. Patients who received more than 10×10⁶ CD34+/kg achieved a more rapid hematopoietic recovery and a shorter hospitalization period.