Infectious Complications In Patients with AL (Immunoglobulin Light Chain) Amyloidosis Undergoing Treatment with High-Dose Melphalan and Autologous Stem-Cell Transplantation (HDM/SCT)

Abstract 2041

High dose melphalan and autologous stem cell transplantation (HDM/SCT) can lead to hematologic and organ responses and improved survival in selected patients with AL amyloidosis. Intrinsic and extrinsic risk factors for infections in these patients include functional hyposplenism, hypogammaglobulinemia, melphalan-induced neutropenia, mucositis, and nosocomial exposures. We performed a retrospective review of 493 patients with AL amyloidosis who underwent treatment with HDM/SCT at Boston Medical Center from August 1994 to August 2009. Patients received outpatient treatment from October 1996 onwards. The objectives of this study were to determine the rate of infections, identify infections leading to treatment-related mortality (TRM, defined as death within 100 days), and compare the impact of patient and treatment characteristics on rates of infection. Microbiologically documented infections after HDM/SCT were identified in 119 patients (24%, n=119/493). The median number of days to post- SCT infection was 8 days (range, 0–47). The mean number of days of body temperature more than 100.5⁰ F (38° C) was 3 (95% CI 1.7–4.31). There were 48 deaths (10%) within 100 days of HDM/SCT. Among patients with documented infection, 25 had TRM (21%, n=25/119). Two hundred and forty five patients had febrile neutropenia. One hundred and forty seven of these had negative cultures. Therefore, the rate of culture negative febrile neutropenia was 60% (n=147/245). Identified pathogens included gram positive bacteria (51%), anaerobic bacteria (15%), gram negative bacteria (13%), fungi (8%) and viruses (6%). The majority of these organisms were identified in blood (50%), followed by respiratory secretions (20%) and stool (15%). Of the positive cultures, gram positive infections included staphylococci (29%), streptococci (10%), and enterococci (10%). C. difficile was the most commonly identified anaerobe, accounting for 11% of the total number of positive cultures. Gram negative bacterial infections included enterobacteriacae (8%) and pseudomonas (3%). Fungal infections included candida species (7%), aspergillus (4%) and pneumocystis (1%). Viral infections included herpes (3%), paramyxoviridae (3%) and cytomegalovirus (0.4%). In the unadjusted bivariate analyses, serum creatinine > 2 mg/dL was significantly associated with increased risk of post-HDM/SCT infections (38% versus 21%, p= 0.0007) with an odds ratio (OR) of 2.27 (95% CI 1.40–3.68). In addition, TRM was found to have a significant association with post-HDM/SCT infections (52% versus 21%, p = < 0.0001) with an OR of 3.82 (95% CI 2.01–7.26). The relative risk of TRM in a patient with documented infection was 3.42 (95% CI 2.02–5.79). In multivariate analyses, serum creatinine > 2 mg/dL remained significantly associated with post-SCT infection with an OR of 2.29 (95% CI 1.41–3.73). No significant association was found for age, gender, cardiac involvement, prior steroid therapy, dose of melphalan, time to neutrophil engraftment, number of organs involved in amyloidosis, or dose of infused CD34+ cells, both in unadjusted and adjusted analyses. In conclusion, serum creatinine >2 mg/dL is a risk factor for infections in patients with AL amyloidosis undergoing HDM/SCT. The relative risk of TRM in a patient with a documented infection was 3.34. A broad spectrum of infections, similar to those reported in other SCT patients, is seen in this population.