Caspofungin plus posaconazole as salvage therapy of invasive fungal infections in immunocompromised patients.

Invasive aspergillosis (IA) is a major cause of mortality in immunocompromised patients. Substantial improvements of treatment have been achieved by the introduction of new antifungal agents including azoles (e.g. posaconazole) and echinocandins (e.g. caspofungin). However, mortality associated with treatment-refractory aspergillosis remains high. Preliminary data suggest that the combination of azoles and echinocandins may increase activity against refractory IA. The objective of the present study was to evaluate efficiency and safety of caspofungin plus posaconazole for salvage therapy in immunocompromised patients. In this monocentric, retrospective study, 31 hospitalised haematopoietic stem cell transplant recipients with IA refractory to primary treatment were treated with a combination therapy of caspofungin 50 mg a day and posaconazole 200 mg four times per day. Efficacy was assessed by signs, symptoms and the degree of pulmonary infiltrate regression. A favourable response was seen in the majority of patients (77%). In two patients (6%), clinical improvement, but no decline in pulmonary infiltrates, was observed. Five patients (16%) did not respond to combination therapy with a fatal outcome in four of them. Combination therapy was well tolerated. No patient discontinued treatment due to toxicity. This study indicates that the combination of caspofungin and posaconazole may provide an effective and tolerable therapy of IA in immunocompromised patients refractory to primary treatment.

Real-time ultrasonography-computed tomography fusion imaging for staging of hepatic metastatic involvement in patients with colorectal cancer: initial results from comparison to US seeing separate CT images and to multidetector-row CT alone.

OBJECTIVES: To prospectively evaluate the role of real-time ultrasonography (US)-computed tomography (CT) fusion imaging (US-CT) in comparison with US seeing separate CT images (US + CT) and multidetector-row CT (MDCT) for the correct staging of hepatic metastatic involvement in patients with colorectal cancer. METHODS: Sixty-four patients with newly diagnosed colorectal cancer and who were referred for abdominopelvic staging before primary tumor resection underwent same-day MDCT, US + CT, and US-CT. Examinations were evaluated on-site by 2 investigators in consensus. Investigators recorded the size and location of detected lesions on segmental liver maps, classified them as being benign, malignant, or indeterminate, and finally assessed the M stage of the liver as being M0, M1, or Mx (indeterminate). All patients underwent surgical exploration including intraoperative US. Reference standard diagnosis was based on findings at surgery, intraoperative US, histopathology, and MDCT follow-up imaging. Differences among investigated modalities were analyzed using McNemar's test. RESULTS: The reference standard verified 109 (45 < or = 1 cm) hepatic lesions in 25 patients, including 65 (25 < or = 1 cm) metastases in 16 patients (M1). Regarding the 45 < or = 1 cm liver lesions, rates for detection were significantly higher (P < 0.05) for MDCT (80%, 36/45) and US-CT (77.8%, 35/45) than for US + CT (64.4%, 29/45); the rate for correct classification by US-CT (71.1%, 32/45) was significantly higher than for US + CT (48.9%, 22/45) and MDCT (31.1%, 14/45) (all P < 0.05). On patient-based analysis, specificity of MDCT (85.4%, 41/48) was significantly lower (P < 0.05) than for US-CT (97.9%, 47/48) and US + CT (93.7%, 45/48); the positive predictive value of MDCT (63.1%, 12/19) was not significantly different (P = 0.27) compared with US + CT (82.3%, 14/17) but significantly lower (P < 0.05) than for US-CT (93.7%, 15/16). In 13 patients (59 lesions) with only benign (stage M0) or coexistent benign and malignant lesions (stage M1), indeterminate lesion ratings and indeterminate liver stagings (Mx) occurred both significantly lower (P < 0.05) with US-CT (3.4%, 2/59; and 0%, 0/13) than with US + CT (11.9%, 7/59; and 23.1%, 3/13) or with MDCT (30.5%, 18/59; and 53.8%, 7/13). CONCLUSIONS: Based on these initial diagnostic experiences, complementary US-CT fusion imaging of small CT-indeterminate liver lesions may have value in staging patients with colorectal cancer, focusing on patients who were likely to harbor only benign or coexisting benign and malignant liver lesions and in whom change of M staging would change the clinical management.

Differentiation of benign from malignant focal splenic lesions using sulfur hexafluoride-filled microbubble contrast-enhanced pulse-inversion sonography.

OBJECTIVE: The purpose of our study was to evaluate whether sonographic characterization of focal splenic lesions could be improved by using low mechanical index pulse-inversion sonography after sulfur hexafluoride-filled microbubble injection. MATERIALS AND METHODS: One hundred forty-seven splenic lesions (68 benign, 79 malignant) in 147 patients (81 men, 66 women; mean age, 51 years) underwent baseline gray-scale sonography and sulfur hexafluoride-enhanced low-acoustic-power pulse-inversion sonography (mechanical index < 0.1). Two site investigators assessed in consensus lesion and splenic enhancement during arterial and parenchymal phases. Four readers (readers 1 and 2, blinded; and readers 3 and 4, unblinded to clinical data) independently reviewed baseline and contrast-enhanced sonograms and provided confidence rating for diagnosis of malignancy or benignancy. Accuracy, sensitivity, specificity, positive and negative predictive values, and areas under the receiver operating characteristic curves (A(z)) were calculated by considering biopsy results or splenectomy (51 patients) or CT or MR images followed by serial sonography 6-12 months apart (96 patients) as reference standards. RESULTS: Benign lesions appeared predominately non- or isoenhancing relative to splenic parenchyma, whereas malignant lesions appeared predominately progressively hypoenhancing. For correct diagnosis of benignancy or malignancy, review of contrast-enhanced sonography after baseline sonography yielded significantly improved diagnostic performance (overall accuracy, 51%, 43%, 70%, and 74% before vs 83%, 81%, 92%, and 91% after contrast-enhanced sonography for readers 1, 2, 3, and 4; p < 0.05; respectively) and significantly improved diagnostic confidence (A(z), 0.770, 0.678, 0.900, and 0.917 before vs 0.935, 0.917, 0.984, and 0.959 after contrast-enhanced sonography for readers 1, 2, 3, and 4; p < 0.05; respectively). CONCLUSION: Sulfur hexafluoride-filled microbubble-enhanced sonography improves characterization of focal splenic lesions with and without the availability of clinical data.

Low number of donor activating killer immunoglobulin-like receptors (KIR) genes but not KIR-ligand mismatch prevents relapse and improves disease-free survival in leukemia patients after in vivo T-cell depleted unrelated stem cell transplantation.

BACKGROUND: The effect of natural killer (NK) cell alloreactivity on outcome of unrelated stem cell transplantation (SCT) remains controversial. Killer immunoglobulin-like receptors (KIRs) recognize human leukocyte antigen C and B epitopes on target cells, thereby regulating NK cell activity. The KIR genes are polymorphic and two broad haplotypes exist: KIR-haplotype A mainly encode for inhibitory receptors and only for one activating (KIR2DS4), whereas the group B haplotype encodes more for activating KIRs (KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS5 und KIR3DS1). METHODS: The impact of KIR ligand mismatch on the number of activating and inhibitory donor KIR genes and on KIR-haplotype was studied on outcome of 142 patients with leukemia, who received standard myeloablative conditioning followed by in vivo T-cell depleted (ATG) unrelated SCT. RESULTS: In a multivariate analysis KIR ligand mismatch had significantly higher treatment related mortality (RR 2.206, P = 0.03), resulting in reduced overall (RR 2.015, P = 0.02) and disease-free survival (RR 1.924, P = 0.03). In contrast, SCT from donors with group A haplotype (P = 0.003) or with low number of activating KIR genes (P = 0.005) resulted in reduced relapse rate with improved disease-fee survival (P = 0.04). This effect was seen only in acute myeloid leukemia/myelodysplastic syndrome and to a less extent in chronic myeloid leukemia. No effect was seen for acute lymphoblastic leukemia. CONCLUSIONS: After in vivo T-cell depleted (ATG) unrelated stem cell transplantation with donors carrying low number of activating KIR genes (group A KIR haplotype), the risk of relapse is reduced and resulted in a significantly better disease-free survival.