Increased Bone Marrow Iron Stores, Severe Mucositis and Large Area under the Curve (AUC) of Profound Neutropenia Predict Severe Infection in 382 Myeloma Patients Undergoing Melphalan - Autologous Stem Cell Transplantation (MEL-ASCT).

Abstract

Background: MEL-ASCT is standard therapy for multiple myeloma (MM) but is associated with severe infections, at times life-threatening. Objective: To determine the risk factors for severe infection (bacteremia, septic shock, colitis, pneumonia) following MEL - ASCT for MM. Materials and Methods: 382 consecutive MM patients (pts) enrolled in our Total Therapy 2 protocol and who received their first MEL - ASCT between 10/1998 and 12/2002 were included. Variables evaluated included age, sex and MM remission status, severity of mucositis and others. Because of the known association between increased body iron stores and infection, pre-ASCT bone marrow (BM) iron stores were also evaluated. The AUC for severe neutropenia (<100 absolute neutrophils (ANC) / mL) was used as a single variable accounting for both the depth and duration of neutropenia. Results: Median age was 56 years (range: 30–76) and 235 pts (62 %) were males. Severe infections developed in 77 pts (20%) including pneumonia (42 pts). Pre-ASCT risk factors for infection by univariate analysis were increased BM iron stores (OR= 3.601; 95%CI 1.795–7.222; p<0.0007) and low platelets counts (OR for -1000 platelets/μL = 0.997; 95% CI 0.994 – 1; p=0.0381). Increased BM iron stores remained significant by multivariate analysis (OR= 3.601; 95% CI 1.795–7.222; p<0.0007). Post-ASCT risk factors that were significant by both univariate and multivariate analysis were severe mucositis (Grades 3–4 by NCI Common Toxicity Criteria) (OR=1.916; 95% 1.093–3.36; p=0.02) and AUC of severe neutropenia (OR= 1.001/unit; 95% 1–1.002; p=0.03). Neither the duration (days with ANC <1000 / mL) nor the depth of moderate neutropenia (AUC < 1000 neutrophils / mL) predicted infection. Conclusion: MM pts scheduled to undergo MEL - ASCT and who have increased BM iron stores, and those who develop severe mucositis and / or prolonged and profound neutropenia following ASCT should be considered at greater risk for developing severe infection. AUC of severe neutropenia is a useful single marker of both depth and duration of neutropenia and should be included in studies evaluating risk for infection in neutropenic pts.