Marisa H. Miceli

Immune reconstitution inflammatory syndrome in cancer patients with pulmonary aspergillosis recovering from neutropenia: Proof of principle, description, and clinical and research implications.

Assessing the outcome of patients with invasive pulmonary aspergillosis by using conventional criteria is difficult, particularly when clinical and radiologic worsening coincides with neutrophil recovery. Usually, it is assumed that this deterioration is related to progressive aspergillosis, prompting changes in patient management. However, its temporal relation with neutrophil recovery suggests that it may be caused by an immune reconstitution syndrome (IRIS). Galactomannan is an Aspergillus‐specific polysaccharide that is released during aspergillosis and is detected by the serum galactomannan test, which has been approved by the United States Food and Drug Administration for the diagnosis of invasive aspergillosis. In this study, the authors used sequential galactomannan testing to distinguish IRIS responses from progressive aspergillosis.

18F-Fluorodeoxyglucose Positron Emission Tomography Contributes to the Diagnosis and Management of Infections in Patients With Multiple Myeloma: A Study of 165 Infectious Episodes

PURPOSE Correctly identifying infection in cancer patients can be challenging. Limited data suggest that positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may be useful for diagnosing infection. To determine the role of FDG-PET in the diagnosis of infection in patients with multiple myeloma (MM). PATIENTS AND METHODS The medical records of 248 patients who had FDG-PET performed for MM staging or infection work-up revealing increased uptake at extramedullary sites and/or bones and joints that would be atypical for MM between October 2001 and May 2004 were reviewed to identify infections and evaluate FDG-PET contribution to patient outcome. RESULTS One hundred sixty-five infections were identified in 143 adults with MM. Infections involved the respiratory tract [99; pneumonia (93), sinusitis (six)], bone, joint and soft tissues [26; discitis (10), osteomyelitis (nine), septic arthritis (one), cellulitis (six)], vascular system [18; septic thrombophlebitis (nine), infection of implantable catheter (eight), septic emboli (one)], gastrointestinal tract [12; colitis (seven), abdominal abscess (three), and diverticulitis and esophagitis (one each)], and dentition [periodontal abscess (10)]. Infections were caused by bacteria, mycobacteria, fungi, and viruses. FDG-PET detected infection even in patients with severe neutropenia and lymphopenia (30 episodes). The FDG-PET findings identified infections not detectable by other methods (46 episodes), determined extent of infection (32 episodes), and led to modification of work-up and therapy (55 episodes). Twenty silent, but clinically relevant, infections were detected among patients undergoing staging FDG-PET. CONCLUSION In patients with MM, FDG-PET is a useful tool for diagnosing and managing infections even in the setting of severe immunosuppression.

Iron overload is a major risk factor for severe infection after autologous stem cell transplantation: a study of 367 myeloma patients

We evaluated the risk factors for infection of 367 consecutive myeloma patients who underwent high-dose melphalan and autologous stem cell transplantation (ASCT). Examination of bone marrow iron stores (BMIS) prior to ASCT was used to evaluate body iron stores. Other variables included age, sex, active smoking, myeloma remission status, severity of mucositis and duration of severe neutropenia post-ASCT (<100 absolute neutrophils counts (ANC)/μl). Median age was 56 years; 61% of patients were males. 140 episodes of severe infections occurred in 116 patients, including bacteremia (73), pneumonia (40), severe colitis (25) and bacteremia with septic shock (two). The infection incidence per 1000 days at risk was 45.2. Pre-ASCT risk factors for severe infection by univariate analysis were increased BMIS (OR=2.686; 95% CI 1.707–4.226; P<0.0001), smoking (OR=1.565; 95% CI 1.005–2.437; P=0.0474) and male gender (OR=1.624; 95% CI 1.019–2.589; P=0.0414). Increased BMIS (OR=2.716; 95% CI 1.720–4.287; P<0.0001) and smoking (OR=1.714; 95% CI 1.081–2.718; P=0.022) remained significant by multivariate analysis. Duration of ANC <100 μ/l (OR=1.129; 95% CI 1.039–1.226; P=0.0069 and OR=1.127; 95% CI 1.038–1.224; P=0.0045 by both univariate and multivariate analysis, respectively) was the only post-ASCT risk factor for infection. Increased pre-transplant BMIS and smoking are significant predictors of severe infection after myeloablative chemotherapy followed by ASCT in myeloma patients.

Mucosa or skin as source of coagulase-negative staphylococcal bacteraemia?

Nosocomial bacteraemia is associated with significant morbidity, mortality, and cost worldwide, and is most commonly caused by coagulase-negative staphylococci (CONS). Establishing the source of CONS bacteraemia is therefore important in the prevention and management of this infection. CONS infections are presumed to originate at the cutaneous sites of central venous catheters (CVCs), a belief that has led to prevention strategies that focus almost exclusively on the skin. However, mucosal colonisation by CONS is well established, suggesting that mucosal sites might be an important source of CONS bacteraemia. We review the published material that evaluates the source(s) of CONS. We included only studies that used a strict definition of CONS bacteraemia, evaluated skin and other potential sources of CONS, and studied the molecular association between CONS blood isolates and their potential sources. Three published reports fulfilled our criteria. In cancer patients with CONS or CONS bacteraemia, most of the colonising strains that had a molecular match with the strain recovered from the blood of the same patient were mucosal isolates; by contrast, no association was seen between CONS blood and skin isolates. Furthermore, in several patient populations evidence was reported of mucosal colonisation by CONS and in several reports experimental and clinical mucosal translocation of CONS with subsequent bacteraemia was documented. Together these data indicate that mucosal sites are an important source of CONS bacteraemia. Clinical strategies for the treatment of patients with a positive blood culture for CONS, the widespread use of antimicrobial-coated CVCs, and maximum barrier protection for CVC insertion should be reassessed, and strategies to decrease mucosal colonisation by CONS should be developed.

Oral mucositis in myeloma patients undergoing melphalan-based autologous stem cell transplantation: incidence, risk factors and a severity predictive model.

Melphalan-based autologous stem cell transplant (Mel-ASCT) is a standard therapy for multiple myeloma, but is associated with severe oral mucositis (OM). To identify predictors for severe OM, we studied 381 consecutive newly diagnosed myeloma patients who received Mel-ASCT. Melphalan was given at 200 mg/m2 body surface area (BSA), reduced to 140 mg/m2 for serum creatinine >3 mg/dl. Potential covariates included demographics, pre-transplant serum albumin and renal and liver function tests, and mg/kg melphalan dose received. The BSA dosing resulted in a wide range of melphalan doses given (2.4–6.2 mg/kg). OM developed in 75% of patients and was severe in 21%. Predictors of severe OM in multiple logistic regression analyses were high serum creatinine (odds ratio (OR)=1.581; 95% confidence interval (CI): 1.080–2.313; P=0.018) and high mg/kg melphalan (OR=1.595; 95% CI: 1.065–2.389; P=0.023). An OM prediction model was developed based on these variables. We concluded that BSA dosing of melphalan results in wide variations in the mg/kg dose, and that patients with renal dysfunction who are scheduled to receive a high mg/kg melphalan dose have the greatest risk for severe OM following Mel-ASCT. Pharmacogenomic and pharmacokinetic studies are needed to better understand interpatient variability of melphalan exposure and toxicity.

Avascular Necrosis of Femoral and/or Humeral Heads in Multiple Myeloma: Results of a Prospective Study of Patients Treated With Dexamethasone-Based Regimens and High-Dose Chemotherapy

PURPOSE To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy. PATIENTS AND METHODS A total of 553 consecutive assessable patients were enrolled onto a treatment protocol consisting of dexamethasone-containing induction chemotherapy, autologous stem-cell transplantation, consolidation chemotherapy, and maintenance with interferon alfa. Patients were randomly assigned to receive thalidomide (269 patients) or no thalidomide (284 patients) throughout the study period. RESULTS With a median follow-up of 33 months (range, 5 to 114 months), AVN of the femoral head(s) developed in 49 patients (9%). Median time to onset of AVN was 12 months (range, 2 to 41 months). Three risk factors for AVN were identified by multivariate analysis: cumulative dexamethasone dose (odds ratio [OR], 1.028; 95% CI, 1.012 to 1.044; P = .0006 [per 40 mg dexamethasone]), male sex (OR, 0.390; 95% CI, 0.192 to 0.790; P = .009), and younger age (OR, 0.961; 95% CI, 0.934 to 0.991 per year; P = .0122). Thalidomide-treated patients had a prevalence of AVN similar to that of the control group (8% v 10%, respectively; P = .58). AVN-related pain and limited range of motion of the affected joint were present in only nine and four patients, respectively, and four patients underwent hip replacement because of AVN. Fluorine-18 fluorodeoxyglucose positron emission tomography failed to detect abnormal uptake in the AVN-affected bones. CONCLUSION AVN is a rare and usually asymptomatic complication during myeloma therapy. Cumulative dexamethasone dose, male sex, and younger age, but not thalidomide, increase the risk of AVN.

Recovery from neutropenia can be predicted by the immature reticulocyte fraction several days before neutrophil recovery in autologous stem cell transplant recipients

The duration of neutropenia (absolute neutrophil count (ANC) ⩽100/μl) identifies cancer patients at risk for infection. A test that precedes ANC⩾100/μl would be of clinical value. The immature reticulocyte fraction (IRF) reflects erythroid engraftment and hence a recovering marrow. We evaluated the IRF as predictor of marrow recovery among 90 myeloma patients undergoing their first and second (75 patients) melphalan-based autologous stem cell transplantation (Mel-ASCT). The time to IRF doubling (IRF-D) preceded ANC⩾100/μl in 99% of patients after the first Mel-ASCT by (mean±s.d.) 4.23±1.96 days and in 97% of the patients after the second Mel-ASCT by 4.11±1.95 days. We validated these findings in a group of 117 myeloma patients and 99 patients with various disorders undergoing ASCT with different conditioning regimens. We also compared the time to hypophosphatemia and to absolute monocyte count⩾100/μl to the time to ANC⩾100/μl. These markers were reached prior to this ANC end point in 55 and 25% of patients but were almost always preceded by IRF-D. We conclude that the IRF-D is a simple, inexpensive and widely available test that can predict marrow recovery several days before ANC⩾100/μl.

Dynamic anatomy of the popliteal artery: might culture affect the outcome of endovascular therapy?

chemia, and there was no neurological deficit. On the second day, the right hand was warm. MDCT 1 month later showed partial thrombosis in the false lumen and good perfusion of the bypass and the LVA. The central portion of the ARSA was occluded as expected, and the right axillary artery was perfused via collaterals (Figure, D). In this case, MDCT showed the anomalies well, guided us to cerebral angiography, and validated the necessity of a carotid–left subclavian bypass while avoiding a bypass to the right subclavian artery. We think MDCT is invaluable in planning of thoracic stent-graft procedures, especially in complicated cases and in patients with anomalous vascular anatomy.

Pulmonary Artery Access Embolization in Patients with Massive Hemoptysis in Whom Bronchial and/or Nonbronchial Systemic Artery Embolization Is Contraindicated

The objective of this paper is to present an alternative therapeutic approach for the treatment of patients with massive hemoptysis in whom bronchial and/or nonbronchial systemic arterial embolization is not possible. We describe a percutaneous procedure for pulmonary segmental artery embolization. Between May 2000 and July 2006, 27 adult patients with hemoptysis underwent percutaneous treatment at our department; 20 of 27 patients were embolized via bronchial and or nonbronchial systemic arteries and 7 patients were embolized via pulmonary artery. Femoral arterial access for systemic artery catheterization and femoral vein access for pulmonary arterial catheterization were used. Gelfoam particles and coils were used for embolization. In this study, we report on three cases of massive hemoptysis from a systemic arterial source in whom bronchial and/or nonbronchial arteries embolization was not possible. Percutaneous embolization via the pulmonary artery access was successful in all three patients. In conclusion, embolization via pulmonary artery is presented as an alternative approach for the management of hemoptysis in patients in whom bronchial arterial embolization is not possible.

PET and PET/CT Imaging in Multiple Myeloma, Solitary Plasmacytoma, MGUS, and Other Plasma Cell Dyscrasias

In MM and related plasma cell dyscrasias, FDG-PET or PET/CT imaging are useful and reliable techniques for assistance in the diagnosis by identifying optimal sites for biopsy, for staging and restaging the tumor, for detecting extramedullary disease, and for monitoring response to treatment. They are equally effective in secretory or nonsecretory disease, with the latter developing with an increasing frequency during the course of the disease, causing difficulty in monitoring disease response or progression.